COURSE PRICE: $39.00
CONTACT HOURS: 6
Wild Iris Medical Education is an approved provider (#PA-54) of continuing nursing education by the Washington State Nurses Association, an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation.
Wild Iris Medical Education (CBRN Provider #12300) is approved as a provider of continuing education for RNs, LVNs, and respiratory therapists by the California Board of Registered Nursing.
Wild Iris Medical Education is an approved provider of case manager continuing education, sponsor code CM2560, by the Commission for Case Manager Certification. Course approval number A206 (ends 12/31/2010).
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
Nancy Evans is a health science writer and editor with more than three decades of experience in healthcare publishing. She served as senior editor at Mosby/Times Mirror, senior editor in the health sciences division of Addison-Wesley, and senior medical editor at Appleton & Lange. She is an honorary member of Sigma Theta Tau International Honor Society of Nursing. A breast cancer survivor since 1991, she currently works with Breast Cancer Fund as health science consultant. She has written and spoken extensively on breast cancer issues in the United States, Canada, Belgium, and New Zealand. Nancy co-produced (with Allie Light and Irving Saraf) the HBO documentary film Rachel's Daughters: Searching for the Causes of Breast Cancer. She is also the co-producer (with Light and Saraf) of Children and Asthma, a KQED documentary film, and the documentary, Good Food, Bad Food: Obesity in American Children.
Copyright © 2009 Wild Iris Medical Education, Inc. All Rights Reserved.
The sections on epidemiology and risk factors are adapted from State of the Evidence 2008: The Connection Between Breast Cancer and the Environment, Janet Gray, ed. (San Francisco: Breast Cancer Fund, 2008). Used with permission.
Upon completion of this course, you will be able to:
The breast, the organ that defines us as sexual and reproductive creatures, is the focus of a battle. What started the war and how the story will end are as particular to each woman as the size and shape of each breast.
—NANCY SNYDERMAN, In The First Look
Breast cancer strikes more women in the world than any other type of cancer except skin cancer. This year more than 1.1 million women will be diagnosed with breast cancer and 400,000 will die from breast cancer. In 2009 in the United States, an estimated 184,000 women will be diagnosed with invasive breast cancer and 40,000 will die of the disease (ACS, 2008). Another 68,000 women are expected to be diagnosed with in situ carcinoma of the breast, a noninvasive cancer that may or may not become invasive over time. Uncertainty often leads these women to choose the same treatment as for invasive cancer, including mastectomy.
Between 1973 and 1998, breast cancer incidence rates in the United States increased by more than 40% (Howe et al., 2001). However, more recent data show a significant decline in breast cancer incidence among U.S. women, although this effect may be relevant only for women over the age of 50 with a particular subtype (estrogen receptor positive, or ER+) of the disease (Ravdin et al., 2007; CDC, 2007).
The recent decline in breast cancer incidence has been largely attributed to the sharp drop in use of postmenopausal hormone replacement therapy (HRT) following the 2002 report linking HRT with increased risk for breast cancer (Ravdin et al., 2007; Robbins & Clarke, 2007). However, it is important to recognize that over the past 30 years, some of the contaminants associated with breast cancer risk—secondhand smoke, certain pesticides, and industrial chemicals—have been reduced or eliminated from our living and/or working environments.
Breast cancer incidence and mortality rates vary widely among racial/ethnic groups, among age groups, and among populations in different geographic areas. Globally, incidence is highest among white women who live in industrialized countries. In the United States, non-Hispanic white women have the highest incidence of breast cancer. American Indian/Alaska Natives have the lowest incidence of the disease (ACS, 2008). Latinas have a much lower incidence of breast cancer than either black or white women, but incidence is rising.
The great majority of women diagnosed with breast cancer are 45 years old or older. Young black women (under age 35) have a higher incidence of breast cancer than their white counterparts and a less favorable prognosis. Their tumors are more aggressive, difficult to treat effectively, and usually larger and more advanced at the time of diagnosis (Newman, 2005; Carey et al., 2006).
Breast cancer also strikes men, who make up about 1% of the total number of cases each year. The incidence of male breast cancer has increased steadily over the past 25 years (Giordano et al., 2004), and nearly 2,000 men were estimated to be diagnosed with breast cancer in 2008 (ACS, 2008). Because breast cancer is a rare disease among men, lack of awareness often results in later-stage diagnosis.
Black women have the highest breast cancer mortality rate of any ethnic group in the United States. Asian Americans, especially Japanese Americans and Chinese Americans, have the best survival rates (Smigal et al., 2006). The reasons for these disparities are not clearly understood, but socioeconomic factors undoubtedly affect both environmental exposures and access to care. American Indians/Alaska Natives not only have the lowest incidence of breast cancer but also one of the lowest mortality rates. However, the American Cancer Society (ACS) urges caution in interpreting these statistics. It is possible that many cases of breast cancer may go unreported, particularly among rural women with limited access to health care in these populations (Smigal et al., 2006).
Statistics on incidence and mortality offer limited understanding of the true picture of breast cancer, particularly among women of color and women by age groups. Although diversity is increasing in the United States, medical research on diverse populations has not kept pace. Much of current breast cancer diagnosis and treatment is still based on white women and looks only at premenopausal (under 50) and postmenopausal (over 50). More research is needed to understand how best to diagnose and treat different types of breast cancer in women of color and women by age group.
Breast cancer is a complex disease caused by the interaction of multiple factors. The two primary risk factors are being female and growing older. Other widely discussed risk factors include family history; primary genetic mutations; radiation exposure such as repeated fluoroscopies (scoliosis or tuberculosis) or radiotherapy for Hodgkin’s disease; reproductive history; and lifestyle factors such as weight gain, alcohol consumption, and lack of physical exercise (Hankinson et al., 2004). However, these factors alone do not account for a large portion of the disease (Kruk & Aboul-Enein, 2006). A growing body of evidence also points to environmental exposures as risk factors for breast cancer.
Family history of breast cancer is a major influence on a woman’s risk of breast cancer. But breast cancer in a first-degree relative (mother or sister) may or may not be related to genetic predispositions such as BRCA1 or BRCA2 mutation. It is important to remember that families share more than DNA. They also share environmental exposures: air, water, food, and living conditions. The largest study of twins ever conducted found that "genetic susceptibility makes only a small to moderate contribution" to the incidence of breast cancer (Baker et al., 2005; Czene et al., 2002).
Ionizing radiation is the best- and longest-established environmental cause of breast cancer and other cancers. In fact, low-dose radiation is twice as likely to cause cancer as high-dose (Brenner et al., 2002). The National Toxicology Program (2005) classifies x-radiation as a known human carcinogen. The International Agency for Research on Cancer (IARC) confirmed these findings based on a study of more than 400,000 nuclear industry workers in 15 countries (Cardis et al., 2005).
Medical imaging is a major source of exposure to ionizing radiation. Over the past quarter century, the amount of ionizing radiation the U.S. population receives each year from medical imaging has increased five-fold (Amis et al., 2007). Radiation increases the risk of breast cancer both by directly damaging DNA and by disrupting normal cellular and intracellular processes. Radiation may also enhance the ability of hormones or other chemicals to cause cancer (Calaf & Hei, 2000; Segaloff & Maxfield, 1971).
Reproductive factors implicated in increased risk for breast cancer include early puberty, late menopause, childlessness, delayed childbearing, and not breastfeeding. All of these factors represent exposure to unopposed estrogen, particularly estradiol (Russo & Russo, 2004). Exposure to synthetic hormones in the form of oral contraceptives and/or postmenopausal hormone replacement therapy also increases the risk of breast cancer (Lund et al., 2007).
One of the most striking trends that may have implications for future breast cancer is the falling age of puberty among U.S. girls. "Girls get their first periods, on average, a few months earlier than did girls forty years ago. But they get their breasts, on average, one to two years earlier" (Steingraber, 2007). Over the past forty years in the United States, the average age of menarche (first menstrual period) has declined only slightly, to 12.6 years for white girls and 12.1 years for black and Mexican American girls.
However, the average age of thelarche (onset of breast development) has dropped to 10 among white girls and to 9 among black girls, a full two years before menstruation begins. Research suggests that a combination of factors is responsible, including low birth weight and premature birth, overweight and obesity, and environmental exposures to endocrine-disrupting chemicals. Obesity rates have tripled over the past thirty years, and thelarche occurs earlier in chubby girls than in lean girls. Although the role of obesity is not clear, it is both a consequence of early puberty as well as a contributor to it.
Childbearing trends have also changed over the past forty years, with many women entering the workforce in their late teens or early 20s and delaying childbirth until after age 30. These women are at higher risk of breast cancer because the breast is not fully mature until after the first full-term pregnancy.
The steady increase in breast cancer incidence following World War II paralleled the proliferation of synthetic chemicals used in industry and consumer products. An estimated 80,000 chemicals are used today in the United States, and another 1,000 new chemicals are introduced each year (EPA, 2007). Many of these chemicals persist in the environment and in our bodies for decades (Nickerson, 2006). Biomonitoring studies measuring for the presence of synthetic chemicals in tissue, blood, urine, breast milk, and body fat (referred to as body burden) can be used to assess human exposure to toxic chemicals. Scientists at the Centers for Disease Control and Prevention (CDC) have found more than 148 chemicals in the bodies of Americans of all ages (CDC, 2005). For example, residue of the pesticide DDT has been found in the bodies of teenagers who were born years after the chemical was banned in the 1970s.
Everyone in the United States is also exposed to non-ionizing radiation (also called electromagnetic fields or EMF). Electrical appliances, electrical wiring, and wireless technologies such as cellular phones, wireless laptops, and personal data assistants (PDAs) are all sources of EMF. The pervasiveness of some of these exposures means that individuals may experience multiple low-level exposures over the course of weeks, months, or even years depending on where they live and work. EMF exposure is associated with increased risk of breast cancer in both men and women (Erren, 2001; Weiss et al., 2005).
A significant body of scientific evidence indicates that exposure to common chemicals and radiation may contribute to the incidence of breast cancer. A survey by the Massachusetts-based Silent Spring Institute indicated that 216 chemicals and radiation sources have been recognized by national and international regulatory agencies as being implicated in breast cancer causation (Rudel et al., 2007).
Certain occupations and professions are associated with increased risk of breast cancer. Nurses are among these higher risk groups, particularly chemotherapy nurses (Coyle & Polovich, 2004). So are chemists, chemical industry workers, clinical laboratory technologists, radiologic technologists, dentists and dental hygienists, physicians, and social workers (Teitelbaum et al., 2003).
These environmental exposures interact in complex ways with genes, hormones, diet, and other lifestyle factors as contributors to the development of breast cancer. It is therefore unlikely that a single direct cause can be established for breast cancer. Instead, breast cancer causation can be seen as a web of interconnected factors, each exerting both direct and interactive effects on cellular and extra-cellular processes in mammary tissue.
Breast cancer arises in the epithelial cells of the mammary gland, which are in constant turnover. These cells are generated continuously by a basal membrane and normally divide, migrate, and differentiate in a tightly controlled process. When internal or external factors interfere, the cells undergo a spectrum of changes, from hyperplasia to pre-invasive to frankly invasive and metastatic cancer. McCance and Huether (2006) describe this as a three-step process:
The most common sign of breast cancer is a painless lump. However, two-thirds of lumps are not cancerous but may be fluid-filled cysts, fibroadenomas (benign tumors), or pseudolumps. Cysts can be aspirated and are generally not malignant. Fibroadenomas need to be biopsied to determine whether they are malignant. Pseudolumps are exaggerated lumpiness, which may be caused by previous breast surgery, fat necrosis (dead fat), trauma from previous breast cancer treatment, or silicon that has migrated from an implant or from an injection site.
Other signs of breast cancers include:
Screening to detect breast cancer can include breast self-examination (BSE), clinical breast examination (CBE), and imaging studies, primarily mammography.
Although BSE has not been shown to improve survival, the fact is that many women (or their sexual partners) discover their own breast cancers. The ACS no longer recommends BSE but suggests that health professionals discuss its potential benefits, limitations, and harms. Women who choose to perform monthly BSE need to be shown the proper technique. Premenopausal women should be advised to examine their breasts seven to eight days after the start of their menstrual period.
Breast Self-Examination (National Cancer Institute).
ACS recommends that women ages 20 to 40 have a CBE at least every three years and that women over 40 have an annual CBE (Smith et al., 2009). Ideally, CBE would be performed by a physician or nurse practitioner who is skilled in the technique and take at least two to three minutes.
The importance of BSE and CBE should not be underestimated. One large, thirteen-year study of more than 39,000 women ages 50 to 59 found that adding mammography screening to CBE and teaching of BSE made no difference in breast cancer mortality. Half of the women had annual mammograms and CBE plus instruction in BSE; the other half had only CBE and instruction in BSE. At the end of thirteen years, there were 107 deaths from breast cancer in one group and 105 in the other (Miller et al., 2000).
Mammography screening is the most widely used method of breast cancer detection. (Mammography is sometimes referred to incorrectly as preventive care. Mammograms do not prevent breast cancer; they are used to detect cancer that has already developed.) Screening mammography aims to detect possible breast cancer in large populations of women who have no symptoms of the disease. Diagnostic mammography aids in the diagnosis of an individual’s suspicious lesion—such as a lump or thickening or other symptom of breast cancer—that was previously detected by self-examination, clinical breast examination, or screening. Any symptom of breast cancer should be thoroughly investigated until a definitive diagnosis is reached, and mammography is an appropriate part of that investigation.
Mammography is most effective in postmenopausal women and has been shown to reduce the risk of dying from breast cancer in women over 50. In this age group, mammography can detect slow-growing (indolent) breast tumors, which are less likely to be fatal, at least two years before they reach palpable size. However, mammography misses fast-growing (interval) cancers, which are more likely to be aggressive and/or fatal.
It is less clear whether mammography screening for women under 50 significantly reduces breast cancer mortality in this age group. Premenopausal women have dense breasts, which impairs the ability of mammography to find tumors.
There is also debate about the value of mammography screening for women over 70. Most clinical trials have excluded women in this age group, even though this population is fast expanding as Baby Boomers age. One trial of women age 80 and older found that screening resulted in earlier diagnosis of breast cancer but no survival benefit (Badgwell et al., 2008).
The majority of breast cancers occur in postmenopausal women, which is why mammography was initially recommended to screen women over age 50. However, official screening guidelines have expanded to include women ages 40 to 49, and even women in their 30s who are high risk for breast cancer. The American Cancer Society (Smith et al., 2009), the National Cancer Institute, and some—but not all—medical organizations now recommend that women begin annual mammography screening at age 40, and even earlier if their family history, genetic predisposition, or previous medical treatment puts them at high risk of developing breast cancer. (Women are considered at high risk of breast cancer if they have either a BRCA1 or BRCA2 mutation or a family history of breast cancer in either a first- or second-degree relative on either the maternal or paternal side.) As a caution, however, some studies have shown that women who are genetically predisposed to breast cancer may be more sensitive to the effects of mammography’s ionizing radiation than women without a genetic predisposition (Andrieu et al., 2006; Gronwald et al., 2008).
In 2007, ACS recommended that women at high risk include breast magnetic resonance imaging (MRI) as an adjunct to annual mammography screening starting at age 30. While acknowledging that MRI is more sensitive in detecting breast cancer in high-risk young women than mammography, ultrasound, or CBE alone, researchers cautioned: "Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation" (Warner et al., 2004; Lord et al., 2007).
The U.S. Preventive Services Task Force (USPSTF) (2002) recommends screening mammography, with or without clinical breast examination, every one to two years for women ages 40 and older. However, the recommendation states that for women ages 40 to 49 "the evidence that screening mammography reduces mortality from breast cancer is weaker" than for women ages 50 and older. It also states that the panel "did not find sufficient evidence to specify the optimal screening interval for women aged 40 to 49."
The American College of Physicians (Qaseem et al., 2007) advises an individualized approach to screening for women in their 40s, stating that there is no consensus on when to begin screening for this age group. They recommend that women ages 40 to 49 years discuss with their doctor the potential benefits and harms of screening based on their individual risk (see below). Women who decide not to have a mammogram should revisit their decision every one to two years.
The United States is the only country in which mammography is recommended for premenopausal women (Moss, 2006). There is growing international debate about whether mammography screening in large populations actually reduces breast cancer mortality rates or, in fact, increases the risk of harm to the women involved, particularly premenopausal women (Gotzsche et al., 2009; Welch, 2008; Anderson et al., 2006; Berrington de Gonzales & Reeves 2005; Baines, 2005). The debate concerns the limitations of mammography and its potential harms, particularly for younger women.
Limitations of mammography include a high rate of false positives and false negatives. Mammograms miss 20 to 54% of breast tumors (Rosenberg, 1998) depending on the patient’s age, breast density, calibration of mammography equipment, and expertise of the technician performing the test and of the radiologist(s) interpreting the mammogram. It also detects abnormalities that are not cancer. False negatives can result in delayed diagnosis. False positives lead to further testing, including surgical biopsies and great anxiety for the patient.
International experts argue that women are not given enough accurate information about the major harm of screening, which is overdiagnosis and subsequent overtreatment of healthy women (Gotzsche et al., 2009). They submit that screening results in 30% more surgery, 20% more mastectomies, and more use of radiotherapy (Gotzsche & Nielsen, 2006) because of overdiagnosis (Vainio & Bianchini, 2002; Raffle & Gray, 2006).
Mammography also detects ductal carcinoma in situ (DCIS), which might or might not eventually become invasive cancer. Treatment for DCIS can include surgery, even mastectomy, because women fear the possibility of invasive cancer. The incidence of DCIS has increased 900% over the past 20 years, largely due to widespread mammography screening and now accounts for more than 20% of all breast cancer (Moss, 2006).
Mammography screening is not a risk-free procedure. It exposes women to low-dose ionizing radiation, the best- and longest-established environmental cause of breast cancer and other cancers. Yet despite the compelling evidence of radiation’s potential harm, mammography continues as a "gold standard" for breast cancer screening and detection in the United States. "The majority of women who participate in mammography screening will not develop breast cancer during their lifetime" (Smith et al., 2003). However, all of them will be repeatedly exposed to a carcinogen, and perhaps 10% will receive a false positive report, resulting in unnecessary surgery and stress.
Mammography also involves another seldom-discussed harm: compression of the breast, which is not only painful but may rupture small blood and lymphatic vessels. If these vessels are near a cancer, compression can cause malignant cells to enter the circulation and migrate to other tissues and organs (Rosser, 2000). Research indicates that malignant tissue is more easily damaged than normal tissue, increasing its vulnerability to the effects of compression (Watmough, et al, 1992).
FINDING AN FDA-CERTIFIED MAMMOGRAPHY FACILITY
Mammography facilities are the most carefully regulated type of radiologic imaging facility. The Mammography Quality Standards Act of 1992 (MQSA) established baseline quality standards for equipment, personnel, and practices in these facilities.
FDA-certified facilities are listed by zipcode at http://www.fda.gov/cdrh/mammography/certified.htm.
Mammography is currently the only technique suitable for widespread breast cancer screening. Other imaging studies in use include magnetic resonance imaging (MRI), ultrasonography, and thermography. However, these are generally used as an adjunct to mammography and primarily for diagnostic rather than screening purposes. Existing research has not established these techniques as stand-alone alternatives to mammography.
Magnetic resonance imaging (MRI) uses a powerful magnetic field to produce detailed images of tissue structures in the breast and has proved ultrasensitive in detecting breast cancer in high-risk women. However, MRI has a high rate of false positives, which can lead to unnecessary biopsies. MRI is also far more expensive than mammography, making it inappropriate for screening large populations.
Ultrasonography (ultrasound) uses high-frequency sound waves to detect breast abnormalities. Ultrasound does not involve breast compression or radiation exposure. When sound waves encounter solid lumps in the breast, they bounce back. Fluid-filled cysts, which are normally not cancerous, do not impede the sound waves. In this way, ultrasound helps distinguish between cysts and solid tumors that may be cancerous.
Ultrasound is currently used for diagnostic rather than screening purposes. However, some experts have suggested adding ultrasound to routine screening of young women at high risk for breast cancer. In one study of nearly 3,000 women, researchers reported that combined screening with ultrasound and mammography would detect an additional 1.1 to 7.2 cancers per 1,000 women in addition to those found by mammography screening alone. However, ultrasound would also substantially increase the number of false positives (Berg et al., 2008).
Research is underway on a newer type of ultrasound, called three-dimensional power Doppler ultrasound. This modality may help radiologists distinguish between benign and malignant breast tumors. It measures blood flow in breast masses, which is generally increased in malignant tumors (LeCarpentier et al., 2008). If proved successful, this new technology could help avoid unnecessary biopsies.
Thermography is a type of Digital Infrared Thermal Imaging (DITI) that uses highly sensitive infrared cameras and computers to create an image of temperature and vascular changes in the breast. Whereas a mammogram shows breast anatomy (structure), a thermogram shows breast physiology (function). Thermography does not involve compression of the breast or exposure to any radiation.
Thermography is based on the concept that increased circulatory activity near precancerous or cancerous tissue raises body temperature in these areas. Although highly sensitive, thermography cannot pinpoint the precise location of a tumor. It also has a high false-positive rate, detecting abnormalities other than cancer such as mastitis, benign tumors, and fibrocystic breast changes. Thermography may also be used to monitor response to treatment (Parisky et al, 2003; Arora et al, 2008; Arena et al, 2003).
The U.S. Food and Drug Administration (FDA) has approved thermography as an adjunct to mammography and physical examination but not as a stand-alone screening technique for breast cancer. In most cases, thermography is not covered by health insurance.
The diagnostic process may include further mammographic evaluation, laboratory tests, and biopsy of the lump, mass, or other abnormality. Biopsy is the most definitive step in the process, establishing whether the abnormality is benign (noncancerous) or malignant (cancerous). If the diagnosis is breast cancer, the pathologist defines the type of cancer and whether it is invasive or noninvasive (in situ).
When a breast abnormality has been detected by mammography or during BSE or CBE, the next diagnostic step is biopsy. There are different types of biopsies, and each has advantages and disadvantages. Biopsies are performed by surgeons, radiologists, and/or pathologists and evaluated by cytopathologists (pathologists who specialize in cancer).
Experience is the most important factor in ensuring an accurate biopsy diagnosis. The more experience a surgeon or radiologist has in performing biopsies, the more likely that the cytopathologist will have an appropriate cell or tissue sample to evaluate. The more experienced the cytopathologist, the more accurate the biopsy results will be.
There are two categories of biopsies for breast tumors: needle biopsies and surgical (open) biopsies.
Needle biopsies are generally outpatient procedures and include:
Surgical biopsies include:
Fine-needle aspiration biopsy uses a small hollow needle to aspirate fluid or cells from a palpable breast lump or mass. It is performed without anesthesia, sometimes in a physician’s office. If clear fluid can be aspirated from the lump, it is diagnosed as a benign cyst. However, if the fluid is bloody or if fluid cannot be aspirated, the cells in the needle are transferred to a slide and sent to the pathology laboratory for review. The incidence of false-positive diagnosis is very low (1 to 2%), but the incidence of false-negative diagnosis is as high as 10%.
Ultrasound-directed needle biopsy is actually an FNA of a nonpalpable lump or mass that can be seen on an ultrasound screen. The ultrasound sensor (also called a transducer) is rubbed over the breast until the lesion becomes visible on the screen, identifying the precise area for needle insertion. It is not a reliable method for evaluating microcalifications, or tiny specks of calcium in the breast.
Stereotactic core needle biopsy uses computerized mammography equipment to obtain tissue samples from nonpalpable abnormalities in the breast that can be seen on a mammogram, such as microcalcifications. The patient is positioned either sitting up or lying on her stomach, depending on the equipment used. If she is lying on her stomach, the breast hangs down through an opening in a special table. The radiologist compresses the breast with a mammography paddle, then pinpoints the area of concern using mammography. After the area is injected with a local anesthetic, the physician makes a tiny cut and inserts a biopsy probe (large hollow needle). The probe removes several small cores of tissue from the area, which are then sent to the pathologist. This procedure generally takes less than an hour. To minimize post-biopsy pain, women are advised to wear a snug-fitting bra and apply ice packs as needed.
Surgical biopsies are also outpatient procedures but are usually done in the hospital rather than a physician’s office.
Wire-localization biopsy is done by a radiologist immediately prior to surgery. It may be done with local anesthesia or conscious sedation. The goal is to pinpoint a mammographic finding, either microcalcifications or a small nonpalpable tumor that is to be excised. Using a mammography machine, the radiologist locates the area of concern and inserts a hollow needle into that area. A thin wire is inserted through the needle into the lesion. Then the needle is withdrawn, leaving the wire in place. The patient is next taken to the operating room. Using the mammogram films (or, in the case of digital mammography, the electronic image), the surgeon uses the wire as a guide, which helps to avoid unnecessary removal of healthy tissue. After the tissue is removed (and while the patient is still on the operating table), the tissue is x-rayed to ensure that it matches the suspicious area on the mammogram and to help orient the pathologist.
Wire-localization is used in patients for whom a stereotactic biopsy procedure is not suitable. It is also necessary if either DCIS or cancer is diagnosed by a stereotactic core biopsy and a part of the breast must be removed.
Excisional biopsy is performed by a surgeon to remove an entire lump or mass plus a small margin of the surrounding normal tissue. It is the most common type of surgical biopsy.
The surgeon may order a number of blood tests to screen for signs of metastasis. For example, these might include sedimentation rate, serum alkaline phosphatase, and calcium levels. Elevated sedimentation rate may indicate disseminated cancer. Elevated serum alkaline phosphatase may signal liver or bone metastases. Hypercalcemia may indicate advanced cancer.
The lungs are a common site for breast cancer metastases. Therefore, a chest x-ray is generally ordered during the diagnostic process. CT scans of the liver and brain are recommended only if metastases are suspected in these areas. Bone scans are done only if laboratory tests suggest the presence of metastases. Positron emission tomography (PET) scans have proved more effective in detecting soft tissue metastases than metastatic bone lesions. However, the PET/CT combination is replacing CT in detecting soft tissue metastases because of its increased effectiveness.
Biomarkers are specific characteristics of tumors that determine which adjuvant treatment would be most effective in preventing recurrence of the cancer. The standard of care is to test breast tumors for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2/neu) oncogene at the time of initial diagnosis.
ER and PR biomarker tests are performed at the time of initial biopsy. Tumors that are ER and/or PR positive can be treated with hormone therapies such as tamoxifen or one of the aromatase inhibitors. These types of tumors are more common in postmenopausal women. Tumors that are ER and/or PR negative do not respond to hormone therapy and must be treated with chemotherapy.
About 20% of women with breast cancer have tumors with high levels of the HER2 oncogene. These tumors tend to be aggressive and fail to respond to conventional chemotherapy or hormone therapy. It is important to establish HER2 status at the outset so that women can have access to Herceptin (traztuzumab), a relatively new type of drug that blocks HER2 in order to stop the growth of cancer cells. Establishing HER2 status ensures that those who are positive are offered Herceptin while those unlikely to be helped by it can avoid its serious side effects. Herceptin is one of a new class of cancer drugs called biological therapies, immunotherapies, or targeted therapies developed to individualize treatments and thereby ensure the greatest possible effectiveness.
Two FDA-approved methods to test for HER2 are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC testing can show how much of the HER2 protein is present on the tumor cell surface, while FISH testing measures the number of copies of the HER2 gene inside each cell.
Women with ER-positive, node-negative breast cancer can undergo the new Oncotype DX test, which tests for twenty-one genetic markers, including ER, PR, and HER2/neu expression in a single tumor sample. In addition, this test can categorize the risk of recurrence as low, intermediate, or high, which helps determine treatment options.
Researchers continue to seek more effective treatments for breast cancer based on molecular genetic characteristics of tumors that fail to respond to existing therapies. A number of other biomarkers are being studied as possible targets for new drug development. One that looks promising is vascular endothelial growth factor (VEGF), a protein that stimulates the growth of blood vessels. This is important because a tumor cannot grow beyond 2 cm unless it develops its own blood supply.
The stage of a cancer (on a scale of 1 to 4, with 4 being the most severe) describes how advanced the disease is and helps determine the course of treatment. Most breast cancers today are detected at Stage 1 or 2. In situ cancer, usually DCIS, is called Stage 0. According to ACS, more than 68,000 cases of in situ breast cancer were expected in 2008, and about 85% of those are DCIS; the rest are lobular carcinoma in situ (LCIS).
There are several different staging systems in use. This section discusses one of the most widely used systems, the TNM Classification System for Breast Cancer, which is one of the oldest classification systems. The T refers to tumor size, N refers to the axillary lymph nodes, and M refers to any distant metastasis. The treatment team uses this system to evaluate the stage of the disease and plan treatment. Once the TNM status is known, the cancer can be assigned a clinical stage.
The smaller the tumor, the lower the risk of cancer recurrence and the higher the chance of survival. If it seems likely that the cancer has spread beyond the breast and lymph nodes, the oncologist may order additional blood tests, x-rays, ultrasound, CT scans, and/or bone scans to check for cancer in other organs.
| Staging Number | Diameter of Tumor |
|---|---|
| Source: TNM classifications are reproduced here and below with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. AJCC Cancer Staging Manual, 6th edition, SpringerVerlag, 2002. | |
| Tx | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor (occult primary) |
| Tis Tis (DCIS) Tis (LCIS) Tis (Paget’s) |
Carcinoma in situ Intraductal carcinoma Lobular carcinoma in situ Paget’s disease of the nipple with no tumor |
| T1 | 2 cm or less in greatest dimension |
| T1mic | Microinvasion 0.1 cm or less in greatest dimension |
| T1a | Tumor more than 0.1 but not more than 0.5 cm in greatest dimension |
| T1b | Tumor more than 0.5 but not more than 1 cm in greatest dimension |
| T1c | Tumor more than 1 cm but not more than 2 cm in greatest dimension |
| T2 | Tumor more than 2 cm but not more than 5 cm in greatest dimension |
| T3 | Tumor more than 5 cm |
| T4 | Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below |
| T4a | Extension to chest wall, not including pectoralis muscle |
| T4b | Edema (including peau d’orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast |
| T4c | Both T4a and T4b |
| T4d | Inflammatory carcinoma |
Lymph nodes are small oval structures that filter lymph as it flows through lymphatic vessels and on to the blood stream. These nodes act to filter out particulate matter, especially bacteria and cancer cells from entering the blood stream. They may, in time become the avenue through which cancer spreads to other parts of the body.
| Staging Number | Node Status |
|---|---|
| Nx | Regional lymph nodes cannot be assessed (previously removed) |
| N0 | No sign of cancer in the nodes |
| N1 | Metastasis to movable axillary nodes |
| N2 | Metastases in ipsilateral axillary nodes fixed/matted to one another, or in clinically apparent* ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis (*Detected by imaging studies [excluding lymphoscintigraphy] or by clinical examination or grossly visible pathologically) |
| N2a | Metastasis in ipsilateral axillary lymph nodes fixed/matted to one another or to other structures |
| N2b | Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis. |
| N3 | Metastasis in ipsilateral infraclavicular lymph nodes with or without axillary lymph node involvement, or in clinically apparent ipsilateral mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node(s) |
| N3a | Metastasis in ipsilateral infraclavicular lymph node(s) |
| N3b | Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) |
| N3c | Metastasis in ipsilateral supraclavicular lymph node(s) |
Metastasis (spread) of the cancer beyond the breast and underarm (axillary) nodes is classified as shown in Table 3. Generally, the smaller the cancer, the less likely it is to have spread. The most common sites for breast cancer metastasis are the bone, brain, lungs, and liver.
| Staging Number | Distant Metastasis |
|---|---|
| Mx | Distant metastasis cannot be assesssed |
| M0 | No distant metastasis |
| M1 | Distant metastasis, including spread to the lymph nodes near the collar bone |
| Stage | T | N | M |
|---|---|---|---|
| *T1 includes T1mic (Microinvasion 0.1 cm or less in greatest dimension). | |||
| 0 | Tis | N0 | M0 |
| I | T1* | N0 | M0 |
| IIA | T0 | N1 | M0 |
| T1* | N1 | M0 | |
| T2 | N0 | M0 | |
| IIB | T2 | N1 | M0 |
| T3 | N0 | M0 | |
| IIIA | T0 | N2 | M0 |
| T1* | N2 | M0 | |
| T2 | N2 | M0 | |
| T3 | N1,N2 | M0 | |
| IIIB | T4 | N0,N1,N2 | M0 |
| Any T | N3 | M0 | |
| IV | Any T | Any N | M1 |
Stage designation may change if postsurgical imaging studies reveal the presence of distant metastases, provided that the studies are carried out within four months of diagnosis in the absence of disease progression and provided that the patient has not received neoadjuvant therapy (chemotherapy or hormone therapy given prior to surgery for breast cancer).
Carcinoma of the breast is not just one disease but a group of different types of cancer that originate either in the duct(s) or the lobules of the breast. Each type has different effects on individual patients, depending on age, general health, access to health care, environmental exposures, and stage of the cancer at diagnosis.
There are two basic categories of breast carcinoma: infiltrating (also called invasive) and noninvasive (also called in situ). Each can occur in either the ducts or the lobules of the breast. Each has the potential to eventually break through the cell wall and invade the surrounding fat. Once invasion occurs, the cancer may metastasize to distant organs, becoming a potentially fatal malignancy.
Parts of the breast and the lymph nodes and lymph vessels near the breast (National Cancer Institute).
| Type | Frequency of Occurrence |
|---|---|
| Source: Giordano, 2008. | |
| Infiltrating (invasive) ductal: | 80–90% |
| Medullary | 5–8% |
| Colloid (mucinous) | 2–4% |
| Tubular | 1–2% |
| Papillary | 1–2% |
| Invasive lobular | 6–8% |
| Noninvasive (in situ) | 4–6% |
| Intraductal (ductal carcinoma in situ) | 2–3% |
| Lobular carcinoma in situ (LCIS) | 2–3% |
| Rare cancers: Juvenile (secretory) Adenoid cystic Epidermoid Sudoriferous |
<1% |
Infiltrating ductal carcinoma accounts for about 80% of cases of breast cancer. Originating in the ducts of the breast, infiltrating ductal carcinoma breaks through the wall of the duct into the breast tissue. It commonly forms a hard lump, which feels much firmer than fibroadenomas (benign breast lumps). On a mammogram, it usually appears as a mass edged with tiny spikes (speculation).
The most common type of noninvasive carcinoma occurs in the ducts of the breast and is called ductal carcinoma in situ (DCIS). About 40 to 60% of DCIS cases go on to become malignant.
Widespread use of screening mammography has dramatically increased the incidence of DCIS since 1973, particularly in premenopausal women. Ninety percent of DCIS is seen on a mammogram as microcalcifications. "Benign calicifications tend to be round or oval, uniform in density, and scattered in the breast tissue. Suspicious microcalcifications, on the other hand, vary in shape, size, form and density and are usually clustered in a linear or segmental pattern" (Northern California Cancer Center, 2008). Based on the mammogram, the radiologist classifies the calcifications as benign, probably benign, indeterminate, or suspicious. Although mammograms can detect calcifications, only a biopsy can determine whether they are DCIS.
Diagnosis of DCIS depends on the pathologist’s interpretation of biopsy results and may be controversial. Second opinions are important because appropriate treatment depends on an accurate diagnosis. Anyone seeking a second opinion needs to take the tissue slides and tissue blocks containing cell samples to a second pathologist. Health insurance may or may not pay for a second opinion.
How best to treat DCIS remains controversial. Some women choose watchful waiting to avoid immediate surgery. However, many choose the same treatment used for invasive cancer, which could include surgery, even mastectomy, plus radiation therapy and possibly a hormonal therapy to prevent recurrence.
Three key factors in determining treatment for DCIS are (1) the extent of disease in the breast or the size of the DCIS as measured by the pathologist; (2) the status of the margins of the biopsy tissue; and (3) the grade of the DCIS. Grade is the most important of these and refers to the structure of the cancer cells and their growth patterns.
Histologic grade describes how closely the cancer cells resemble normal cells. Low-grade tumor cells look more like normal cells and grow more slowly than high-grade cells, which look irregular and unlike normal cells. High-grade tumor cells in DCIS are thought to be more likely to become invasive over time.
Nuclear grade refers to the rate at which the cells proliferate (divide to form more cells). Cells that proliferate rapidly are faster growing and more aggressive than those that divide more slowly. The nuclear grade is based on the percentage of cells that are dividing.
Although high-grade DCIS is more likely to become invasive, it can be controlled more effectively than low-grade DCIS, which can be more widespread within the breast.
Mastectomy is generally recommended if either of the following conditions apply:
Sentinel lymph node biopsy may be recommended for those patients with DCIS who choose mastectomy. If cancer cells are found in the sentinel node(s), axillary dissection can be completed at the same time as the mastectomy (Sakr et al., 2008).
Infiltrating (invasive) lobular carcinoma originates in the lobules of the breast, where the milk is produced before it enters the ducts of the breast. It accounts for about 6 to 8% of breast cancer cases. It generally does not form a lump but more of a thickened area. Lobular carcinoma is also more difficult to see on a mammogram than ductal carcinoma. A number of research studies have linked invasive lobular breast cancer with use of hormone replacement therapy (HRT).
Lobular carcinoma in situ (LCIS) is much less common than DCIS but carries a similar risk of becoming malignant.
Some unusual types of breast cancer are more difficult to diagnose and treat. These include triple negative breast cancer, inflammatory carcinoma, Paget’s disease of the breast, and breast cancer during pregnancy or lactation.
Women whose tumors are ER-negative, PR-negative, and HER2/neu-negative are said to have triple negative breast cancer. This is a rare subtype of breast cancer more common among young women and those of African descent. It is highly aggressive with distinct patterns of metastasis and does not respond to hormone therapy or targeted therapy. However, it does respond to some types of chemotherapy. Anthracyclines, such as doxorubicin (Adriamycin), and taxanes, such as paclitaxel (Taxol), have been used successfully, particularly as neoadjuvant therapy. Most BRCA1-associated breast cancers are triple negative. Brain and other visceral metastases are more common in triple negative breast cancer than are bone metastases. Trials are underway to test newer targeted therapies including VEGF and others (Anders & Carey, 2008).
Inflammatory breast cancer (IBC) is the most malignant form of breast cancer and accounts for less than 3% of all cases (Giordano, 2008). This aggressive subtype may be mistaken for an infection because it is characterized by swelling, pain, and reddened, warm skin over the breast. The inflamed appearance is caused by invasion of cancer cells into the subdermal lymphatic channels. If antibiotics do not rapidly change the appearance, biopsy should be performed. IBC is usually classified as Stage IIIB or Stage IV, indicating that it has metastasized to distant sites at the time of diagnosis.
Like triple negative breast cancer, IBC is more common among young African American women (Houchens & Merajver, 2008). Once a uniformly fatal disease, IBC can now be treated more effectively. Research and a multidisciplinary team approach to treatment now offer hope of fifteen-year survival in 20 to 30% of cases (Low et al., 2004). Neoadjuvant chemotherapy is the standard of care. For those women whose tumors are HER2-positive, Herceptin is added to the regimen.
Paget’s carcinoma is a very rare cancer. It primarily affects the nipple, presenting as itching or burning with superficial erosion or ulceration. In some cases, there is no breast mass. Like inflammatory breast cancer, Paget’s disease of the breast is often misdiagnosed as dermatitis, delaying proper diagnosis. If cancerous changes are confined to the nipple, the prognosis is excellent. If a breast mass is present, the cancer may have spread to the axillary nodes or beyond. Treatment may include lumpectomy or simple mastectomy, depending on the extent of disease. Lumpectomy would be followed by radiation therapy to reduce the risk of recurrence.
Breast cancer during pregnancy or breastfeeding is rare—only 1 in 3,000 cases—but it does happen (Giordano, 2008). Even though the tumor can be felt, both the woman and her doctor may mistake it for normal pregnancy changes in the breast, delaying diagnosis. This delay means that in two-thirds of cases, the cancer has spread to the lymph nodes before it is discovered. Depending on the stage of the pregnancy at the time of diagnosis, some women may choose to terminate the pregnancy before beginning treatment. Other women may choose to have a mastectomy during pregnancy and follow up with chemotherapy after the baby is born. However, chemotherapy during the second and third trimester appears to be safe. Again, these are choices unique to each individual.
Research suggests that there is a slightly increased risk of mortality for women who become pregnant after breast cancer because of the surge in estrogen during pregnancy. However, that increase disappears somewhere between two and five years after diagnosis. One research study showed that pregnancy after breast cancer does not appear to affect survival for women with Stage I and II cancer who wait four years before becoming pregnant. That study also showed that breast cancer prior to pregnancy increases the risk of miscarriage (Valentgas, 1999).
For many years, breast cancer was assumed to be a localized disease, and the treatment of choice was also localized: a radical mastectomy. However, that assumption and the radical mastectomy have been abandoned by modern medicine. "The long preclinical growth phase [eight to ten years] and the tendency of breast cancers to metastasize have led clinicians to believe that most breast cancer is a systemic disease at the time of diagnosis" (Giordano, 2008). This does not minimize the importance of local control of the cancer, however. A large meta-analysis of seventy-eight clinical trials evaluating the extent of surgery and the use of radiation therapy found that improved local control at five years improved overall survival at fifteen years (Clarke et al., 2005).
Treatment of breast cancer today generally includes some combination of localized (surgery and radiation therapy) and systemic treatments (chemotherapy, hormonal therapy, targeted biological/immunotherapy). Surgery is often the primary treatment for breast cancer, followed by radiation therapy. Depending on a number of factors, chemotherapy and/or hormone therapy may be administered over weeks or months. The medical oncologist may recommend one or more of these therapies, depending on the patient’s age and the stage and other characteristics of the tumor.
The goal of systemic treatment is to destroy stray cancer cells that have moved beyond the breast to other areas of the body and to achieve long-term remission of the cancer. Medical scientists used to think that a tumor had to reach a certain size before cells moved into the bloodstream and traveled to other parts of the body. However, research has shown that cancer cells can migrate out of the breast very early in the development of a tumor. This is why chemotherapy is recommended for premenopausal women with breast cancer even if there is no evidence of cancer in the lymph nodes.
Radiation therapy, chemotherapy, hormone therapy, and targeted biological therapy are referred to as adjuvant therapy. However, the sequencing of surgery and chemotherapy is changing. Some practitioners prefer to administer chemotherapy and/or hormone therapy before surgery to remove the tumor, which is called neoadjuvant therapy. Neoadjuvant therapy may shrink large tumors, thereby enabling patients to have a lumpectomy rather than a mastectomy. It also enables the oncologist to evaluate a drug’s effectiveness in an individual patient.
Timing of neoadjuvant therapy also has implications for lymph node assessment (see below). Current practice is to perform sentinel lymph node biopsy (SLNB) before chemotherapy so as to avoid a false-negative result. If cancer cells are found in the sentinel node(s), then a standard axillary node dissection can be done at the time of the major breast surgery (Giordano, 2008). If no cancer cells are found in the sentinel node(s), the patient can avoid axillary lymph node dissection, and reduce the risk of lymphedema, a painful, disfiguring chronic swelling that can affect the entire arm and hand.
Surgery is a cornerstone of treatment for breast cancer. Whether it precedes or follows chemotherapy or hormonal therapy, however, depends on a number of factors, including the stage of the cancer, the age of the patient, and the preferences of the treatment team. Women with breast cancer may have a lumpectomy or one of three types of mastectomy (surgery to remove the breast).
Depending on the patient’s age, general health, and the size, type, and stage of the tumor, she may need only surgery and perhaps radiation therapy. But many women, especially those who have not reached menopause, may need to consider adjuvant systemic therapy: chemotherapy, hormonal therapy, or targeted biological therapy such as Herceptin. They may also want to consider one or more of the complementary therapies discussed later in the course.
Timing of surgery for premenopausal women in relation to the menstrual cycle may affect long-term prognosis, but this theory remains controversial. Some studies have found that timing of surgery can improve long-term survival of breast cancer, while other studies found no effect. Some research shows that having breast surgery during the luteal phase of the cycle (eighteen to twenty days after the first day of the menstrual period) can improve survival significantly. A meta-analysis of the literature on this issue also found that surgery during the luteal phase improved outcomes (Chaudhry et al., 2006). Establishing the luteal phase through serum analysis is more exact than counting the days after the last menstrual period (Kontos & Fentiman, 2006). Some surgeons argue that there’s no "proof" that this timing of surgery improves survival odds—and there isn’t. But there is no evidence that this timing is harmful, so some women choose to schedule their surgery in this phase.
Also called segmental mastectomy or breast-conserving surgery, lumpectomy is the removal of the tumor and a narrow margin of the surrounding tissue. Although this procedure has wide acceptance as a primary treatment for early breast cancer, recent studies show an increase in mastectomy, particularly in those women who had MRI in addition to mammography. MRI may find tumors in the breast that are not cancer, leading women to request mastectomy.
Experts estimate that as many as two-thirds of women with breast cancer are good candidates for lumpectomy rather than mastectomy, but only about one-third of women choose lumpectomy. There may be several reasons for this. Women diagnosed with breast cancer naturally want to "get rid of it," and psychologically, having the breast removed seems the best way to do it. But because breast cancer cells may already have left the breast and spread to other parts of the body, mastectomy offers no guarantee that the surgeon "got it all."
Lumpectomy may not produce a good cosmetic result for a woman who has a large tumor in her small breast. However, large tumors sometimes can be reduced prior to surgery either by neoadjuvant radiation or chemotherapy, making lumpectomy a viable option. This also shows whether the tumor is responding to the therapy.
The current standard of care is to follow lumpectomy with five to six weeks of daily radiation therapy (five days a week) to destroy any remaining cancer cells that could cause recurrence or metastasis. Although radiation therapy does not appear to increase survival rates (with the possible exception of high risk women—those with large tumors and extensive node involvement), it does reduce the risk of recurrence on the operated side. Some women, particularly older women with very small, slow-growing tumors (less than 1 cm), may choose not to have radiation therapy. (See "Radiation Therapy" below.)
There are three types of mastectomy: simple, modified radical, and radical. In a simple mastectomy, only the breast is removed. A modified radical mastectomy removes the complete breast and the axillary lymph nodes but leaves the chest-wall muscles intact. A radical mastectomy involves removal of the entire affected breast, the underlying chest muscles, and the lymph nodes under the arm (axillary node dissection). Radical mastectomies are generally not performed in the United States.
Some women with cancer in one breast choose to have the other breast removed at the time of their mastectomy. This is called a bilateral mastectomy, and removal of the other breast is considered a prophylactic (preventive) measure. Prophylactic mastectomy reduces the risk of breast cancer recurrence; but it is not an absolute guarantee because it is impossible to remove all breast tissue from the chest wall.
In addition to breast surgery, many surgeons will suggest axillary node dissection (also called lymph node dissection or lymph node sampling). Lymph node sampling is performed for two reasons: first, to tell whether the cancer has spread beyond the breast, and second, to remove any cancerous nodes. Oncologists use this information in staging the tumor as a basis for planning chemotherapy treatment.
Axillary lymph node dissection involves removal of a large number of axillary lymph nodes for examination by a pathologist. Formerly a part of all breast cancer surgery, axillary dissection has been replaced in many cases by a newer procedure called sentinel lymph node biopsy.
Sentinel lymph node biopsy (SLNB) is also called sentinel lymph node dissection. This newer procedure offers a less traumatic alternative for determining whether the cancer has spread beyond the breast. SLNB is most appropriate for women with early breast cancer who have a low risk of lymph node involvement. Women over 50 may not be good candidates for SLNB because normal age-related changes may have altered the drainage of lymphatic fluid, making the sentinel node unreliable as a marker of lymph node involvement. Women who have neoadjuvant chemotherapy to shrink a large tumor are also poor candidates for SLNB because chemotherapy may have scarred and inflamed the tissue, altering the flow of lymphatic fluid. Physical examination, imaging studies, and tumor size help determine the most appropriate type of lymph node sampling.
SLNB is easier to tolerate and recover from than axillary node dissection. Usually done at the same time as either lumpectomy or mastectomy, SLNB can be done under local anesthesia. Before the tumor is removed, a radioactive substance is injected into the area surrounding the tumor. About an hour later, in the operating room, the surgeon injects a special dye near the tumor and makes a small incision in the underarm area. By tracking the path of the dye and the radioactive substance, the surgeon can identify and remove the "sentinel" node (or up to three nodes), which cancer cells from a breast tumor would reach first.
The node(s) are sent to the pathology laboratory for examination while the patient is still in surgery. If no cancer cells are found in the sentinel node(s), no further nodes are removed—only the tumor itself. If cancer cells are found, however, the remaining nodes are removed and analyzed using standard axillary dissection technique.
Research has shown SLNB to be 97% accurate in women with tumors three centimeters or less in predicting whether remaining lymph nodes contain cancer cells (Krag et al., 2007).
Choosing SLNB greatly reduces the potential for lymphedema if no cancer cells are found in the sentinel node. Choosing not to have any lymph node assessment may be reasonable in the following circumstances:
Lymphedema is not considered to be a curable condition due to the permanent damage to, or absence of, various lymphatic system components…. [Therefore,] a subclinical lymphedema exists after surgery or radiation therapy.
—BRIAN D. LAWENDA, 2009
Lymphedema is an all-too-common complication of axillary node dissection and radiation therapy. Primary lymphedema results from a congenital and/or hereditary condition. Breast cancer treatment is the leading cause of secondary lymphedema. When the patient has both axillary surgery and radiation, the risk of lymphedema rises from 6% to 48%. With SLNB and radiation therapy, the risk rises to 23% (Lawenda et al., 2009).
Lymphedema has lifelong consequences that include progressive swelling, soft tissue fibrosis, neurologic changes (pain and/or paresthesias), and infection (Lawenda et al., 2009). Women who are overweight are at higher risk for the development of lymphedema (Armer, 2008), as are women under age 60 (Armer & Stewart, 2005) and women with a bra cup size of C or larger (Pezner, 1985).
It is critical to recognize lymphedema at the earliest possible stage to educate the patient and initiate treatment to prevent worsening of the condition. Table 6 describes the stages of lymphedema.
| Stage | Type |
|---|---|
| Source: Lawenda et al., 2009 | |
| 0 | Asymptomatic or latency stage. |
| 1 | Reversible lymphedema. Soft, pitting edema that can be completely resolved by prolonged elevation of the limb. |
| 2 | Spontaneously irreversible lymphedema. Clinically evident pitting edema, positive Stemmer sign. |
| 3 | Lymphostatic elephantiasis. Severe fibrotic response, tissue volume, papillomas, cysts, fistulas, and hyperkeratosis. Recurrent infections. |
Preoperative measurement of both arms provides an essential baseline for postoperative volume comparison and detection of postoperative swelling. A 5% increase in arm volume should signal the possible development of lymphedema (Armer, 2008). In addition, nurses should be alert to patients’ self-reported symptoms of heaviness or tightness in the arm, aching or other discomfort, restricted range of motion, and swelling in the arm of adjacent upper quadrant of the trunk (Armer et al., 2003). Although the color and temperature of the skin are normal, the skin folds may deepen and a positive Stemmer sign may be present. (A positive Stemmer sign is a condition in which the skin of the dorsum of the fingers and toes cannot be lifted or only lifted with difficulty in comparison with the skin on the uninvolved limb [Zuther, 2005].)
Risk of lymphedema is lifelong after breast cancer surgery or radiation therapy. Therefore, patients need to reduce risks of developing the disorder through precautionary measures such as:
Many physicians don’t talk about lymphedema before surgery, and when it does appear, they tell the patient she just has to live with it—that there’s nothing to be done. However, treatment is available and is best started at the first sign of swelling. The goal of treatment is to decrease the swelling as much as possible and maintain the limb at its smallest size. This helps prevent or eliminate infections. Treatments include complete decongestive therapy, manual lymph drainage, and compression, as prescribed by a physical therapist or other lymphedema specialist (see "Resources").
Patients who choose to have a mastectomy may want to consider reconstructive plastic surgery. Like every other aspect of breast cancer treatment, this is the patient’s personal choice based on fully informed consent. Ideally, patients would consult the surgeon, one or more plastic surgeons, women who have had reconstructive surgery, those who have chosen to wear a prosthesis, and those who are comfortable with only one breast. One helpful resource is Nancy Bruning’s Breast Implants: Everything You Need to Know, 3rd edition.
Breast reconstruction involves important decisions: when to have the surgery and whether to have an implant (silicone or saline) or a tissue transfer (called an autologous implant) from another site on the body, usually the abdomen or the back. Taking tissue from another body site may create weakness or loss of sensation in that site, so patients need to weigh all the risks and benefits before making a decision.
Whether the reconstruction is done immediately after the mastectomy or later, the breast surgeon and the plastic surgeon need to confer before the mastectomy to have the best possible cosmetic result. If the patient is going to have chemotherapy, the oncologist may recommend delaying reconstruction until after chemotherapy is finished. This avoids risk of infection from the surgery that would necessitate antibiotics and possibly interfere with the chemotherapy.
Despite reports in the popular media, silicone implants have not been proven safe. Many women have had debilitating and disfiguring complications from breast implants. Saline implants may not be risk-free either because the saline is contained in a silicone shell. Premenopausal women who plan to become pregnant after breast cancer need to know that an implant may reduce the supply of breast milk (Bondurant et al., 1999).
Many women choose reconstructive surgery because having two breasts helps them forget about having cancer and makes them feel "whole" again. Others just want to be symmetrical and don’t want to bother with a removable prosthesis. Some women choose not to have reconstruction after mastectomy. One young woman, diagnosed at age 28, chose not to have reconstruction, saying, "I’ve always felt okay about the way I look with just one breast. It helped that my husband supported my decision. I think doctors almost automatically assume that young women will want reconstruction and don’t really discuss the option of not reconstructing or not using a prosthesis" (Morello-Frosch, 1997).
Each woman has the last word on how she wants to look after a mastectomy. It’s her breast, her chest, her life—she’s in charge.
Radiation therapy is generally recommended after lumpectomy for early breast cancer (and sometimes after mastectomy) to destroy any stray cancer cells that could cause recurrence or metastasis. Unusually large tumors may be radiated before surgery to shrink them and thereby avoid mastectomy.
Research has shown that radiation therapy after lumpectomy reduces the risk of local recurrence of the cancer by about 10%; however, it does not significantly improve overall survival. Some research has linked radiation therapy with increased deaths from heart disease (Darby et al., 2005). A large study in England showed that radiation therapy slightly decreased local recurrence but increased the risk of death from heart problems. Patients with left-sided breast cancer or pre-existing heart problems are at highest risk for radiation-induced heart disease (Patt et al., 2005). Chemotherapy treatment with adriamycin or other anthracycline drugs or with Herceptin also increases the risk of heart problems. Therefore, decisions about radiation therapy should also consider what, if any, chemotherapy is proposed.
For older women and women of any age who have a low risk of recurrence, the risk of radiation therapy may outweigh the benefits. Women age 70 or older or those with less than five years’ life expectancy may choose not to have radiation therapy and instead use hormone therapy such as tamoxifen (Smith & Ross, 2004). They should be advised of the possible increased risk of local recurrence.
The American Society for Clinical Oncology recommends radiation therapy after mastectomy for patients who have four or more positive lymph nodes, tumors larger than 5 centimeters, or locally advanced cancers (Recht, et al, 2003).
Radiation treatments are usually given every day for five to six weeks. Depending on where a patient lives and works, such a regimen may or may not be practical or feasible. Women who live or work in a city may find scheduling daily radiation treatments fairly simple. Others may find that distance, transportation, or employment issues make such a regimen difficult or even impossible; they may choose mastectomy as an alternative. Some women who choose not to have radiation therapy feel that a mastectomy gives them added "insurance" against recurrence or metastasis. Others are comfortable just having a lumpectomy and no radiation. The decision is up to the patient, based on consultation with her treatment team.
Scheduling radiation appointments early in the day helps patients avoid delays and waiting room time. Many women continued to work throughout radiation therapy.
The two most common side effects of radiation therapy are fatigue and skin irritation. In most cases, neither effect is noticeable until at least halfway through the six weeks of treatment.
Fatigue signals a need for more rest—and patients need to pay attention to that signal rather than try to be "superwomen." The fatigue may last for several weeks after treatment.
Skin reactions to radiation can range from a mild "sunburn" effect to severe rash and swelling. No two people have the same reaction. Nurses can provide advice and printed guidelines on skin care (National Cancer Institute, 2007). Some products such as aloe gel may help relieve symptoms but also may stain clothing, so patients are advised to dress accordingly. Some breast cancer patients in the San Francisco Bay Area report success with a cream called ching wan hung, available from Chinese herbal pharmacies and intended to reduce pain, swelling, and blistering.
Advise the patient to:
Other side effects of radiation, although rare, can include swelling and hypersensitivity in the radiated breast, especially just before the menstrual period. Some women may experience sharp pains or aching on the affected side, which may be wrongly interpreted as a sign of recurrent cancer.
Radiation therapy can also have serious long-term complications. As mentioned earlier, radiation therapy increases the risk of lymphedema, which is chronic and can appear even years after treatment. Other serious side effects include rib fractures, radiation pneumonitis (inflammation of the lungs), and neurological problems such as motor weakness of the hand or arm.
Radiation therapy is high-dose exposure. If cancer recurs in a breast that has been radiated, mastectomy is the only localized treatment option.
Radiation therapy for breast cancer increases the risk of secondary malignancies, including leukemia, lung cancer, second breast cancer, esophageal cancer, or a rare type of cancer called a sarcoma. These cancers may develop ten or more years after treatment in the tissue that has been radiated (Roychoudhuri et al., 2004; West et al., 2005; Huang & Mackillop, 2001; Shuryak et al., 2006). The prognosis for sarcoma is poor.
Decades of research indicate that the female hormone estrogen is linked to the development of breast cancer and to the likelihood of its recurrence. That is why surgically removing the ovaries (oophorectomy) can sometimes cause breast cancers to regress. Drugs that interfere with the production of estrogen can reduce the chance of recurrence or metastasis of breast cancer. Two groups of drugs that affect estrogen production are called selective estrogen response modulators (SERMs) and aromatase inhibitors (AIs).
Selective estrogen response modulators include tamoxifen (Nolvadex), goserelin (Zoladex), fulvestrant (Faslodex), toremifene, and raloxifene (Evista). Only tamoxifen, fulvestrant, and toremifene have been approved for adjuvant breast cancer treatment. Goserelin is sometimes used in certain types of metastatic breast cancer.
Since the 1960s, tamoxifen (Nolvadex) has been prescribed for women with estrogen receptor–positive breast cancer to reduce the risk of cancer in the opposite breast. Tamoxifen does not benefit women with estrogen receptor–negative cancer. Tamoxifen is taken twice daily for up to five years. The National Cancer Institute (NCI) has advised that tamoxifen should not be taken longer than five years because after that time it may increase the risk of breast cancer.
Unlike chemotherapy, tamoxifen does not cause hair loss or nausea, but it does have side effects, some of which can be life threatening. The most common side effects are hot flashes, vaginal dryness, sexual dysfunction, depression, and mood swings. In some women, tamoxifen can cause cataracts, fractures, blood clots in the lungs or legs, stroke, and/or endometrial (uterine) cancer. Many women also report that tamoxifen interferes with their memory and their ability to concentrate, symptoms similar to "chemo brain," and research validates these reports (Bender et al., 2007; Mitsiades et al., 2008).
Tamoxifen is not appropriate for women with HER2-positive tumors because it may stimulate the growth of cancer cells.
Depending on the age of the patient and tumor characteristics, the oncologist may recommend both tamoxifen and a course of chemotherapy. Studies have shown that chemotherapy and tamoxifen should be used sequentially rather than concurrently, usually beginning with chemotherapy.
Raloxifene (Evista) is a newer drug than tamoxifen. It was approved in 1997 to prevent osteoporosis after menopause. However, early studies of raloxifene also suggested that the drug reduced the risk of breast cancer without the risk of uterine cancer that tamoxifen carries, but with a similar risk of blood clots. Subsequent studies confirmed these findings, so raloxifene is sometimes prescribed to reduce the risk of breast cancer in women who do not have breast cancer but are at high risk for developing the disease.
Aromatase is an enzyme produced in body fat and other tissue, particularly the breast. After menopause, when the ovaries no longer produce estrogen, aromatase converts hormones called androgens, produced by a woman’s adrenal glands, into estrogen. This conversion serves as the body’s main source of estrogen but also increases estrogen levels and thereby raises the risk of breast cancer.
Aromatase inhibitors (AIs), true to their name, inhibit (block) the conversion of androgens to estrogens, thereby limiting the amount of estrogen that can reach cancer cells. This can lead to regression or stabilization of a tumor. However, AIs also act on other estrogen-sensitive tissues, which may account for some of the drugs’ side effects, such as muscle and joint pain, and bone loss, which can increase fractures of the hip, spine or wrist.
Aromatase inhibitors are currently used to treat postmenopausal women with hormone-responsive breast cancer, that is, cancer that is either estrogen receptor–positive or progesterone receptor–positive.
Three aromatase inhibitors (AIs) have been approved by the FDA for use in advanced cancer: anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). Anastrozole has also been approved as adjuvant therapy for postmenopausal women with hormone-responsive positive breast cancer.
Anastrazole (Arimidex) was the first AI tested against tamoxifen in a major clinical trial, and it proved more effective than tamoxifen in protecting against recurrence of the cancer and against developing cancer in the other breast. Anastrozole also improved survival compared to tamoxifen. However, like all drugs, anastrozole has side effects, which include increased risk of osteoporosis and fractures, memory problems and lack of concentration, muscle and joint pain, high cholesterol, and heart problems.
Although initially recommended as a first-line treatment only for women with advanced or metastatic breast cancer, later studies showed that anastrozole is appropriate as adjuvant treatment for some postmenopausal women with estrogen-positive breast cancer. Doctors may recommend anastrozole particularly for those at high risk for the kinds of side effects caused by tamoxifen (endometrial cancer, blood clots, stroke).
Like anastrozole, letrozole (Femara) has proved more effective than tamoxifen in terms of survival benefits and quality of life. Letrozole is currently approved as a first-line therapy only for those with locally advanced or metastatic breast cancer and is often recommended after tamoxifen has failed to keep the cancer in remission.
Side effects of letrozole are not common but can occur, including nausea and vomiting; muscle or bone pain; fatigue; headache; dizziness; muscle weakness; swelling of the hands, feet, or lower legs; loss of appetite; constipation; diarrhea; abdominal pain; hot flashes; and cough.
Clinical trials of all hormonal therapies for breast cancer are under way in the United States and abroad. As new information becomes available, treatment recommendations may change, so it is always best to check the most current information available.
In the United States, administration of cancer chemotherapy generally occurs after surgery for breast cancer; this is called adjuvant chemotherapy. However, women with large tumors may receive chemotherapy before surgery to shrink the tumor and perhaps avoid a mastectomy. This is called neoadjuvant chemotherapy and is used more widely in Europe.
Statistically, chemotherapy treatment can reduce the relative risk of recurrence by about one-fourth to one-third. For example, a woman with a larger, more aggressive tumor and more lymph nodes involved might have a 75% chance of recurrence without chemotherapy. With chemotherapy, her statistical risk of recurrence might be reduced to around 50%. In contrast, a woman with a small tumor and negative lymph nodes might have her statistical risk of recurrence reduced from 12% to 8%. So the higher the statistical risk of recurrence, the greater potential benefit from chemotherapy.
The medical oncologist generally determines a patient’s statistical risk of recurrence and the percentage of benefit she might expect from chemotherapy. This does not mean that the tumor will respond according to statistics, and chemotherapy may have a greater or lesser effect on the risk of recurrence than predicted (see Stephen Jay Gould’s essay The Median Isn’t the Message for a personal perspective on cancer statistics [http://www.cancerguide.org/median_not_msg.html]).
Detailed discussion of individual chemotherapy drugs or even classifications of drugs is beyond the scope of this course. Clinical trials continue to yield new drugs and new information on older drugs, all of which makes this a constantly changing field.
Chemotherapy treatment is generally given in cycles of either every twenty-one or twenty-eight days over the course of three months, six months, or one year, depending on the individual patient. The time between treatments allows the bone marrow to recover. Women at high risk of recurrence and younger women sometimes receive chemotherapy as often as every two weeks. This regimen is called dose-dense chemotherapy and can improve survival compared with conventional dose regimens. However, it is a physically difficult regimen to tolerate (Giordano, 2008).
Different chemotherapy regimens are associated with particular risks, so each woman needs to ask about the risks of the regimen her oncologist recommends. When deciding about chemotherapy treatment, women also need to consider its side effects and "quality of life" factors. Other women who have been through chemotherapy can be helpful, and so can local support groups or on-line chat rooms.
Most of the chemotherapy drugs used to treat breast cancer have toxic side effects. Nausea and vomiting, fatigue, and hair loss are the most common. Increased risk of infection and anemia are other possible side effects. Specific drugs have specific side effects too numerous to describe here.
Nausea and vomiting. Fortunately for patients, the nausea and vomiting related to chemotherapy can now be minimized or sometimes eliminated all together by a number of newer medications such as Zofran (odansetron), Kytril (granisetron), and Ativan (lorazepam). These medications have fewer side effects than older antinausea drugs.
Hair loss. Most (but not all) breast cancer chemotherapy regimens cause hair loss, which is traumatic for most cancer patients, but especially for women. Women cope with hair loss in different ways: camouflage with hats or scarves, wearing a wig, or shaving their heads at the first sign of hair loss. Many find that "bald is beautiful," and some patients may need a reminder that cancer is nothing to be ashamed of. Women have said, for instance: "I didn’t know how beautiful my face was until I lost my hair." With hair loss, it’s important to wear a hat, cap, or scarf to protect the scalp when out in the cold or sun.
Limp libido, infertility, early menopause. Chemotherapy can also affect sexuality, intimacy, and fertility. It can cause vaginal dryness, pain, and discomfort during sexual activity. Premenopausal women may be catapulted into menopause by chemotherapy. The younger the patient, the more likely her periods will return when chemotherapy is finished. The closer she is to the age of natural menopause, the more likely chemotherapy will bring about menopause, with hot flashes, vaginal dryness, mood swings, and sleep disturbances. There may also be increased risk of osteoporosis.
Cognitive effects (also called "chemo brain"). Almost every woman who’s experienced chemotherapy talks about chemo brain, the forgetfulness, loss of concentration, and fuzzy thinking that often accompany chemotherapy. Research has shown that these symptoms are real, not imaginary (Stewart et al., 2008; Hurria et al., 2006; Inagaki et al., 2007). Before beginning chemotherapy, it may be helpful for patients to talk with chemo veterans to see how they coped with this side effect. Some women find chemo brain a minor nuisance; others have such serious memory and attention problems that they stop driving until treatment is finished.
Infection. Chemotherapy drugs lower resistance to infection because they attack the white blood cells that are part of the body’s immune system. Reducing risk of infection during chemotherapy means taking extra precautions: avoiding crowds and people (especially children) with colds or other illnesses, frequent handwashing, wearing gloves while gardening, attending promptly to any cuts or burns. Frequent blood tests are needed to monitor white blood cell count. Patients may be prescribed a drug called Neupogen (filgrastim) to boost white blood cells
Anemia. Chemotherapy drugs can cause anemia because they attack the immature red blood cells in the bone marrow. Most people with cancer are at least mildly anemic, but chemotherapy and radiation therapy can exacerbate the problem. Anemia can result in fatigue, dizziness, shortness of breath, and chills. Adding green leafy vegetables and lean red meat to the diet can relieve some anemia, but supplementary iron or blood transfusions may also be necessary. At one time, erythropoietin (Epogen) was used to correct the problem. However in March 2007, the FDA issued a public health advisory indicating that the use of Epogen and other erythropoiesis-stimulating agents (ESAs) increased the risk of death and tumor growth and failed to reduce the need for blood transfusions. ESAs do not have FDA approval for treatment of fatigue in people with cancer or HIV/AIDS or in surgical patients.
High-dose chemotherapy, an expensive and debilitating procedure, has been used widely for women with advanced breast cancer. The procedure involves removing (harvesting) bone marrow or stem cells from the patient before chemotherapy, giving the patient chemotherapy in doses 5 to 30 times higher than standard chemotherapy, then returning the harvested stem cells to the patient. The stem cells are expected to produce replacement cells for those destroyed by chemotherapy. However, research has shown that the transplants are no more effective than standard chemotherapy for most patients (Farquhar et al., 2005).
Until recently, breast cancer chemotherapy has been largely "one size fits all" or at least "one size fits most." But cancers, like the people who have them, are very individual, and individual tumors may be resistant to certain chemotherapy drugs or drug combinations.
Thus, tumors may be tested before a patient receives chemotherapy to see which drugs show evidence of resistance (chemoresistance testing) or effectiveness (chemosensitivity testing). This gives patients the best chance for effective therapy and eliminates the use of ineffective drugs and their toxic side effects. Such tests (called assays) are controversial and not foolproof, but many oncologists believe they are useful. Sometimes called designer chemo, these assays are also expensive—between $1,500 and $2,000—and insurance may not cover the cost.
The assays require fresh tumor cells, which means that the surgeon must know in advance of surgery whether such tests will be done in order to prepare the tumor specimen properly. There is more than a slight chance that the cells will fail to grow in the test tube.
Chemoresistance assays are used to identify ineffective drugs, those that will not slow the growth of cancer cells. The most widely used of these is the Extreme Drug Resistance (EDR) assay, offered by Exiqon, a laboratory in Tustin, California. Exiqon has conducted a number of clinical trials on the EDR assay, one of which enrolled 102 breast cancer patients. In this trial, after fifty months, those who received drugs to which their tumors had shown low resistance had an 80% survival rate while those who had intermediate or extreme resistance to even one of their treatment drugs had a 45% survival rate.
Chemosensitivity assays test cancer drugs to see which ones will kill the cancer cells, not just inhibit their growth. The Weisenthal Cancer Group in Huntington Beach, California, performs these assays for patients who have received no treatment as well as those who have relapsed. Rational Therapeutics, in Long Beach, California, also conducts chemosensitivity testing.
For most of the twentieth century, cancer drugs were cytotoxic (cell-killing) drugs. Aimed at killing any cancer cells that have escaped the primary site, chemotherapy also kills normal healthy cells, especially those that grow and divide rapidly (such as hair and epithelial cells in the mouth, the lining of the digestive tract, and the reproductive tract). In many cases, cytotoxic drugs also damage the immune system, the body’s major defense against infection and disease.
Researchers have long sought alternatives to cytotoxic drugs that don’t have toxic side effects and that work with the body’s immune system instead of against it. Rather than killing cancer cells (and other cells), these biological therapies (also called immunotherapies or targeted therapies) would interrupt the cancer process in some way. In 1998, research into biological therapies began to pay off, and the FDA approved the drug Herceptin (traztuzumab) for metastatic breast cancer.
Herceptin was a true breakthrough in the treatment of metastatic breast cancer. Though not a cure and not effective for all women, Herceptin is a targeted approach to treatment that may benefit as many as a third of all women diagnosed with breast cancer, particularly those with aggressive tumors.
Herceptin interrupts the cancer process by deactivating the protein on the surface of cancer cells that fuels the growth of those cells. The protein is produced by the HER2/neu oncogene, which is "overexpressed" in the tumors of some women with breast cancer. Because Herceptin does not kill healthy cells, it does not cause nausea, vomiting, diarrhea, and hair loss associated with standard chemotherapy. When used as a first-line therapy for metastatic disease, however, Herceptin is usually combined with Taxol (paclitaxel), a cytotoxic drug that can have significant side effects. As a second- or third-line therapy (after prior chemotherapy has failed), Herceptin can be used as a single agent. In all cases, it is administered in weekly intravenous infusion.
The most common side effects of Herceptin appear to be fever, chills, and pain during infusion. These effects usually diminish with subsequent treatments. The most serious toxicity in some patients treated with Herceptin is cardiac dysfunction, an effect also noted with doxorubicin and other anthracycline drugs used in cancer chemotherapy. This is why Herceptin is not given with an anthracycline drug but instead with a taxane (Taxol or Taxotere).
Pretreatment testing of breast tumors for the HER2/neu oncogene is now the standard of care. The test does not require live cells but can be done using a specimen stored in a paraffin block at the hospital’s pathology laboratory.
Researchers think that cancer vaccines can help stimulate T-cells to resist the growth and spread of cancer cells. Unlike traditional vaccines, cancer vaccines are designed to program the immune system to treat the disease and prevent recurrence. This approach has proved successful in treating metastasized melanoma, a potentially fatal skin cancer. A number of vaccines for breast cancer and other cancers (prostate cancer, kidney cancer, and lymphoma) are in clinical trials, but none has been approved as yet. Vaccines and other biological therapies would be much less toxic than chemotherapy and radiation, both of which damage the immune system.
A tumor cannot grow beyond two centimeters unless it generates its own blood supply, a process called angiogenesis. Scientists believe that shutting down this process in a tumor will prevent it from growing, hence the name antiangiogenesis drugs. Endostatin and angiostatin are two such drugs that have been successful in shrinking tumors in mice; they are now being studied in humans in clinical trials. More than twenty other angiogenesis agents are also in clinical trials for various kinds of cancer, but their safety and effectiveness will not be completely understood for years to come.
Before new cancer drugs can be marketed in the United States, they must be approved by the FDA. The FDA requires that drugs be tested in clinical trials, a three-phase process that follows earlier laboratory and animal testing. Phases I and II test for safety and dosage in small numbers of patients, sometimes twenty or fewer. If results of these two phases suggest that the drug is safe and effective in treating a cancer, the drug company then moves into a Phase III trial. A Phase III trial compares a new drug or new treatment regimen to the standard treatment and involves many cancer patients, usually several hundred, to see whether the early results hold true when the drug is given to many more people. By giving the drug to many patients, doctors can see what percentage of patients are helped by the drug and what side effects to expect.
Understanding what a clinical trial is and how to find out what clinical trials are available is particularly important for cancer patients because of the ongoing research into less toxic, more effective treatments. Clinical trials are also called research studies or research protocols. According to the National Cancer Institute, a cancer clinical trial is "an organized study conducted in people with cancer to answer specific questions about a new treatment or a new way of using an old treatment."
Most cancer treatment trials are randomized trials, which means that patients are assigned to receive either the new drug being studied or the standard treatment considered most effective for that particular cancer. Trials are usually double blind; that is, neither the patient nor the doctor knows which drug the patient is getting. This avoids any bias on the part of the doctor or the patient.
There are both advantages and disadvantages to enrolling in a clinical trial. Advantages include state of the art clinical care, usually paid for by the trial sponsor, and access to promising drugs before they are approved. Disadvantages include potential insurance problems, possible unexpected side effects, and the need to travel to the trial site.
Physicians may be able to provide information about clinical trials in breast cancer, but patients also have access through the Internet and by calling individual pharmaceutical companies. Some doctors may be reluctant to encourage participation in clinical trials because it may mean losing patients to another practice.
When a cancer diagnosis throws us over the edge of the cliff, conventional treatment can seem like our safety net. Our oncologist prescribes a treatment for us and off we go. But there is no toll-free number for complementary cancer care; a "Complementary Treatment Coordinator" is not standing by with a ready-made plan. There’s just you and this vast ocean of information.
—CAROL O’TOOLE, 1999
Many people with cancer choose one or more complementary therapies to reduce the side effects of chemotherapy and radiation, to relieve pain, to boost their immune system, or to speed the healing process. Complementary therapies include unconventional (non-Western) treatments—such as nutritional supplements, dietary changes, herbal remedies, exercise, yoga, massage or acupuncture—used in addition to conventional Western medicine. Nutritional supplements are the most frequently chosen complementary therapies. None of these therapies has been shown to cure cancer, but some have been shown to relieve symptoms and improve quality of life.
Alternative therapies are unconventional treatments used instead of conventional medicine. Alternative therapies are too numerous and too controversial for the purposes of this course.
Complementary therapies differ from Western medicine in at least three ways. First, they are probably not covered by health insurance. Second, there is little scientific evidence about their effectiveness because they have not been well studied. Third, unlike Western medicine, which treats a specific problem by standard methods such as surgery, radiation, or chemotherapy, complementary therapy views the patient as a whole entity and the body as more than the sum of its parts. This holistic approach is also referred to as mind-body medicine or integrative medicine.
Michael Lerner (1994) suggests a starting point, which he calls "the vital quartet of unconventional cancer treatment":
He describes this vital quartet as "intensive forms of health promotion, which, practiced with prudence, are unlikely to be harmful and may promote both quality of life and the possibility of life extension."
Most Western doctors agree that eating a healthful diet makes sense for anyone, and especially for people with cancer. Eating healthy can speed recovery, strengthen the immune system, restore energy, and reduce risk of cancer recurrence.
The basics of eating healthy include:
Food is the best source of vitamins and minerals, but sometimes food fails to provide enough of certain nutrients, especially during recovery from cancer and its treatments. Patients should be cautioned not to take megadoses of vitamins and minerals because some (for example, some B vitamins) can be toxic in large doses.
More than half of all cancer patients take one or more supplements, with or without their doctor’s approval. Patients should be advised to discuss taking antioxidants such as vitamins C and E with their oncologist and complementary health practitioner. Taking these supplements during treatment may decrease the effectiveness of chemotherapy or radiation.
Supplement use is also controversial because of limited research. However, the Office of Dietary Supplements at the National Institutes of Health was established in 1995 to create scientific databases on vitamins, minerals, and herbs.
Physical approaches in complementary therapy can include exercise, relaxation techniques, massage and other body work, and yoga. Exercise is essential for recovery and maintaining good health. Regular physical exercise after a cancer diagnosis can have a positive effect on quality of life, including physical, functional, psychological, and emotional well-being.
"Climbing the wall" stretching exercises are often prescribed to help restore range of motion in the arm after lymph node dissection. However, patients should be alert for any signs of swelling, tingling, or pain (all signs of lymphedema) and should seek treatment immediately if these symptoms occur. Some swelling in the initial weeks after surgery is normal.
Post-cancer exercise programs are tailored to the individual patient. She can start slowly and then modify the program as she recovers strength and energy. Programs can be developed around one or more of these types of therapies:
A few innovative practitioners are beginning to combine complementary therapies with conventional medicine, a practice called integrative or holistic medicine. Andrew Weil is one of the best-known practitioners of integrative medicine. This Harvard-trained physician heads the Institute of Integrative Medicine at the University of Arizona and is author of several books, including the bestseller Spontaneous Healing.
Keith Block also practices integrative or holistic medicine to treat cancer patients. His program at the Block Medical Center in Evanston, Illinois, and at the Cancer Institute at Edgewater Medical Center in Chicago integrates conventional care, a low-fat/high fiber organic diet, mind-body therapies, and physical care individualized to meet the needs of each patient. This type of integrative medicine may become more common and accessible if research supports the efficacy of such an approach and/or if consumers demand this type of care.
Few words strike greater fear than "You have cancer." For many people, this seems like a death sentence. Add the word breast and nightmare images flash, not only of death but of disfigurement. A host of emotions follow the fear: shock, disbelief, anger, wonder. These are all normal reactions, even though many women survive breast cancer and go on to lead full lives.
Patients facing a diagnosis of breast cancer need support and information about treatment options and what to expect in the short-term. Many find comfort in talking with survivors of breast cancer and joining a professionally facilitated support group of women who are currently in treatment. Nurses can also provide essential information to women with breast cancer.
WHAT WOMEN NEED TO KNOW ABOUT BREAST CANCER
Breast cancer is a crisis but it is NOT an emergency. You have time to learn about this disease and the options for treatment; indeed, it is essential to educate yourself about breast cancer. You have time for second opinions and even third opinions. You have time to talk with other women who have faced this diagnosis and survived.
You have choices about treatment for your breast cancer. There are often other options than mastectomy. Treatment choices depend on many factors, including your age, the size of your breast, and the size of your tumor. If your tumor is small, lumpectomy may be an alternative. It may not be necessary to remove your lymph nodes. However, it is important to know whether the cancer has spread to the nodes.
Chemotherapy, hormone therapy, and/or radiation therapy are other choices that may be recommended. You may also want to consider complementary therapies such as acupuncture, Ayurvedic medicine, and herbal/nutritional supplements.
Complementary therapies are not cures but ways to promote healing and help with the symptoms and side effects of other treatments.
You are not alone. There are at least 2.6 million American women living with breast cancer today. Many lead active, productive lives, much as they did before breast cancer. Most never forget what it felt like to hear the words, so most are willing to reach out to others with breast cancer.
You will have information overload—and that’s OK. Learning all you can about breast cancer helps you regain a sense of control and gives you a sound basis for making important decisions about your future. The Internet has made that easy. But there’s a point where you must let your conscious brain rest and listen to your intuition.
There is no one correct decision for everyone—only the decision that is right for you.
Take someone with you to all appointments if possible, someone who can act as your advocate and your recorder. The emotional impact of cancer can interfere with your ability to hear and remember what doctors say, so ask a friend or family member to go with you and tape record or take notes at each appointment.
You need a complete record of your breast cancer journey. Learning that you have breast cancer can be one of the most stressful times in your life. Stress can make you forgetful, so keep a written record of your breast cancer diagnosis and treatment: test results, pathology reports, findings of the radiologist based on mammograms or other imaging studies, any communication with hospitals and doctors. You will need these records to get second (and more) opinions, to deal with insurance companies, and to be sure the records are completely accurate.
You also need to keep a log of medical appointments from the initial visit throughout your follow-up care. Many people keep this information in a notebook, along with self-monitoring notes about pain, reactions to medications, fatigue, and other symptoms.
Many women also keep a journal about their breast cancer experience. Writing about your feelings can aid in the healing process, and help to integrate the cancer experience into the rest of your life.
It’s your journey. You decide how to take the journey and with whom to travel. Friends, family and your health care team can help but only you can decide what’s best for you.
Source: Evans, 2009
Providing written information to women newly diagnosed with breast cancer is important because stress and anxiety can lead to forgetfulness. The National Cancer Institute, the American Cancer Society, and other organizations listed in the "Resources" section have many materials available for patients.
I miss my breast every day. Being one-breasted is not difficult, but that doesn’t mean it’s easy. There is one moment in every day—when I remove my pajamas to step into the bathtub in the morning or when I pull my shirt over my head to undress for the night—when I am still shocked to see my asymmetrical chest.
—MERIJANE, In The First Look
Many women fear that breast cancer will affect their relationships with others, particularly their sexual partners, and it can. This is particularly true for women who choose mastectomy, but even some women who choose lumpectomy are surprised at the impact of the scar.
Concerns about relationships and sexuality are particularly important to young women with breast cancer. Many young women are single and seeking to establish relationships. Almost all young women are working, just beginning to build a career. Some have no health insurance. Some are just starting families, and others have very young children. Breast cancer is a very different issue for young women who have what was long considered an older woman’s disease.
Young women also are likely to be diagnosed at a later stage and to have more aggressive tumors. Chemotherapy treatment may impair fertility and/or the ability to breastfeed if they do have children. These women can now find information and peer support through the Young Survival Coalition.
A diagnosis of breast cancer can create powerful feelings of loss: loss of control, loss of sense of oneself as a healthy woman, possible loss of a breast, and perhaps even loss of life. Grief is the normal response to that loss and can include feelings such as denial, anger, bargaining, and depression. Grieving can help the patient come to terms with the actual and potential losses and move toward healing.
Cancer is the ultimate loss of control. People feel that the body they have lived in for so many years has betrayed them. Someone who has taken good care of herself, eaten right, exercised—in other words, followed all the rules—may ask, "Why me?" Why should an otherwise healthy woman have breast cancer? The question has no easy answer. Fortunately, a healthy lifestyle may have delayed the progression of breast cancer and may make the treatments ahead easier to tolerate.
Many women feel justifiably angry about their breast cancer diagnosis; it certainly isn't fair. In the best of all possible worlds, none of us would ever have cancer. Unfortunately, we live in a country where cancer is the leading cause of death in people under age 85 (Jemal et al., 2005).
Society equates breast size and shape with the essence of female identity. That's why millions of women have had plastic surgery to enlarge their breasts, sometimes with tragic results. The thought of losing one or both breasts to cancer threatens self-image and can lead to anger and/or depression. These are normal reactions. Given time, however, most women realize that they are more than just their breasts. Being alive is what matters.
Once breast cancer becomes a fact of life, women may feel guilty and blame themselves for something they did or failed to do. Not only is this not helpful, it’s probably not true. The biggest risk factors for breast cancer are unchangeable: being female and getting older. Patients may find it useful to discuss their thoughts and feelings about what caused their breast cancer in a support group, with survivors, with a therapist/counselor, or with a supportive health care provider.
The feelings that surround breast cancer differ with each woman. Some take longer than others to work through and resolve these feelings. It is normal and natural to become totally consumed by the process, and being patient with oneself is helpful when someone doesn't bounce back quickly. Just as it takes time to recover from the loss of a friend or loved one, recovering from the losses that cancer represents also takes time.
Patients need time to heal emotionally as well as physically. Although breast surgery may be routine for the surgeon, it is highly unusual for the patient. Cancer changes lives forever, and it generally takes a while to understand what those changes will be. This can be difficult for patients who are still getting used to the idea of having a life-threatening illness and undergoing treatment. Treatment itself also requires rest and time for healing and recovery, as it can be an assault on the body's defenses.
Support groups are helpful to many women with breast cancer. Being able to talk openly with friends and family can evoke an enormous outpouring of love and support. Accepting these offerings can comfort both the patient and the givers. People who care may need for the patient to tell them how best to help.
A cancer diagnosis also can cause people to distance themselves from the patient, at least initially, often out of fear of the disease, as though it were contagious or because they don’t know how to react. Patients can prepare for this reaction and learn to focus on their immediate issues of treatment and recovery.
The patient’s first decision is typically whom to tell, how to tell, and how to deal with the reactions they receive. Breaking the news that you have breast cancer is difficult and painful, particularly when you can scarcely believe it yourself. But not telling family and others who care is difficult too. Keeping a secret takes time and energy that the patient will need for getting through the weeks and months ahead.
It's important to pick the right time and place to break the news: time enough for asking and answering questions and a place where it's okay to cry and hug and talk openly. Loved ones will be experiencing some of the same feelings as the patient—shock, fear, anger, denial—plus empathy for the situation and sorrow at the possible loss this disease might cause.
Family and friends may not know how to respond even though they may want to offer support. What they want most of all is for the patient to be okay again. Patients who explain their situation as they learn more about it help loved ones deal with the news and show them how they might help. Patients may keep a list of those who offer, "Let me know if there's anything I can do." These people can be called on for helpas needed: for a ride to doctors’ appointments, to run errands, to prepare food, or just to drop by for a visit. Family and friends are often delighted to be of help.
The patient is the only one who can decide whom to tell and how much to tell them. Some women may not want to "go public" about their breast cancer but instead confine the news to immediate family and friends. The choice is very personal for each woman.
Breast cancer disrupts every part of life, and work is no exception. Diagnostic tests, doctors' appointments, surgery, and other treatments can mean weeks or months away from the job. Ideally, employee and employer work together to develop a plan for needed absences and a return to work. Some employers can be understanding about employee illness. For example, companies may offer a "sick pool" in which employees who use up their sick days can take additional time through other employees’ donations of sick days to the pool.
A few employers may prove difficult to deal with. Some women have experienced discrimination or even dismissal because of their cancer. Such a practice is now illegal, but it can happen anyway. After firing a woman with breast cancer, one company rewrote their insurance policies to limit coverage for cancer.
Those employed at the time of a cancer diagnosis may have the right to keep their job, and benefits may be protected by federal and state law, depending on the number of employees at a company. The federal Family Medical Leave Act (FMLA) of 1993 applies to companies with fifty or more employees. FMLA specifies who is eligible, when leave can be taken and for how long, whether it will be paid or unpaid, how leave will affect benefits, returning to work, and other issues. State law may supersede FMLA if the state law provides better benefits for the employee.
Employees also have the right to privacy. Any information a patient supplies to an employer about illness or any other medical information must NOT be placed in personnel files but in confidential files with access restricted to only those with a legitimate need to know. Patients also have the right to examine their personnel files.
Employee rights for a person with cancer are protected by the Health Insurance Portability and Accountability Act (HIPPA). This law addresses pre-existing conditions, forbids discrimination against employees based on health status, and guarantees availability and renewability of health insurance coverage to certain individuals.
Cancer casts a long shadow. Anyone diagnosed with cancer lives with the possibility of recurrence. Although many women survive breast cancer and live out a normal life span, others do not. That is why each new pain or other symptom raises the specter of recurrence or metastasis until the symptom disappears or is found to be something other than cancer. Learning to live with uncertainty is part of recovery from cancer, and it is different for each individual.
Patients should be encouraged to focus on wellness—taking good care of body, mind and spirit—by eating a healthy diet, getting enough sleep and exercise, paying attention to symptoms, and getting regular checkups. Wellness also includes grieving one’s losses, whether the loss of a breast, loss of a relationship, or loss of the sense of control. It means seeking support when you need it. Many women continue with a support group after treatment has ended. Others seek individual counseling and psychological support.
When walking the tightrope between fear of recurrence and getting on with life, each new ache or pain can trigger anxiety. This is normal, but it can also be immobilizing. The American Society for Clinical Oncology (ASCO) recommends that patients see their doctor immediately if any of the following symptoms occur and/or persist:
These symptoms might not signal a recurrence of cancer, but they call for prompt evaluation.
Some symptoms may just be the after effects of treatment. For example, some women report a pseudorheumatism three to four months after chemotherapy has ended. Others experience costochondritis, arthritis-like pain in the space between the breasts where the ribs and breastbone connect.
If breast cancer recurs, it usually happens within the first five years after diagnosis and is most often suspected or discovered by women themselves.
The American Society for Clinical Oncology (ASCO, 2006) recommends the measures listed below for routine follow-up care after breast cancer. Other tests may be done, depending on the individual situation and what the patient and her physician decide is necessary.
Endometrial biopsy (removal and microscopic examination of sample tissue from the lining of the uterus) is not recommended by ASCO unless the patient has vaginal discharge or bleeding.
Additional blood tests, chemistry panels, tumor markers, and imaging studies are not recommended unless the patient has symptoms.
Breast cancer patients also need to stay current with screenings for other types of cancer. For example, depending on age and family history, patients should also have a colonoscopy to screen for colon cancer. Colorectal cancer kills more women than breast cancer, and it is the only cancer that can be seen early enough to be completely cured by surgery alone.
Breast cancer that recurs may be local, regional, or metastatic. Treatment may be local/regional or systemic and can range from surgery alone to high-dose chemotherapy. The choice depends on several factors, including but not limited to:
Cancer that recurs within two years after the initial treatment tends to be more aggressive than cancer that recurs later.
Breast cancer most commonly recurs locally—in or near the site of the original tumor, for example in or around the scar. When recurrent cancer is confirmed, the physician orders blood tests and a bone scan to determine whether the cancer has spread beyond the breast. Any cancer that recurs locally is regarded as aggressive and resistant to treatment. When cancer recurs locally after lumpectomy, mastectomy is the preferred treatment.
When breast cancer cells have spread to the adjacent lymph nodes (usually in the axilla) or to the chest wall, it is termed a regional recurrence. This may require surgical treatment and/or localized radiation therapy as well as systemic treatment.
Cancer in a different part of the breast or in the contralateral (opposite) breast may be a new cancer, which is called a second primary. This cancer may be an entirely different cell type and may be treated successfully with surgery alone.
Once breast cancer has spread to distant organs (Stage IV), cure is no longer possible. However, palliative care measures including radiation, hormone therapies, and/or surgery (such as oophorectomy) to control hormone levels can significantly improve survival. The most common metastatic sites for breast cancer are the bone, brain, lungs, and liver. Breast cancer that metastasizes to the bone can be treated with targeted radiation therapy. Therapies such as Aredia and Strontium 89 can help reduce the pain of bone metastases. Patients with cancer in the bone should be cautioned about the increased risk of fracture.
Patients with recurrent or metastatic breast cancer need support and understanding more than ever, not only from family and friends but from health professionals as well. They need to be able to talk openly about their cancer, their feeling and concerns, their care preferences, and their decisions about treatment and when to stop treatment. This can be very stressful for some people, which is why many patients seek support groups of other patients with recurrent cancer; they understand each other.
Cancer reminds us to take care of unfinished business, not only in personal relationships but in practical matters, sometimes referred to as "getting one’s affairs in order" (see box below). Although family and friends may be uncomfortable with these discussions, they can be reassuring to the patient. As Michael Lerner (1994), president and founder of Commonweal writes:
My general experience is that preparing for the possibility of death does not interfere with the fight for life at all—in fact, it can enhance it, because you have taken away the worry of not having dealt with these very practical matters. Taking care of the things you want to take care of actually releases energy for the fight for life.
PRACTICAL END-OF-LIFE CONCERNS
Nurses and other health professionals can provide information about resources to help with these concerns. They can also help family members understand why discussing these issues doesn’t mean that the patient is "giving up" and may actually be comforting to the patient. For example, some people think calling in hospice means giving up and that it will shorten the client’s survival. However, a recent study of more than 4,000 patients suggests the opposite: the mean survival was twenty-nine days longer for hospice patients than for nonhospice patients (Connor et al., 2007).
People also may mistakenly think that hospice is a place. Although there are some hospice residential facilities, most hospice care takes place in the client’s home or the home of a loved one. However, hospice care also occurs in hospitals and nursing homes.
When patients ask "How long do I have?" physicians cannot answer with certainty. One study showed that only 20% of physicians’ prognoses regarding time of death were even approximately accurate (Christakis, 2000). More than half were overly optimistic. Estimates are that more than 1 in 10 patients who enter hospice care are discharged alive by their own choice. Columnist Art Buchwald entered hospice after refusing dialysis for kidney failure—and left five months later to go home and write another book. He died nearly a year later. The real question is: What do you want to do with whatever time you have left?
American Cancer Society
http://www.cancer.org
University of Texas MD Anderson Cancer Center
Complementary/Integrative Medicine Resources
http://www.mdanderson.org/departments/cimer
Intercultural Cancer Council
http://iccnetwork.org
National Cancer Institute
http://www.cancer.gov/cancertopics/
Oncology Nursing Society
http://www.ons.org
Annie Appleseed Project
Complementary and Alternative Therapies
http://www.annieappleseedproject.org
Breast Cancer Action
http://bcaction.org
Breast Cancer Fund
http://www.breastcancerfund.org
Breast Cancer Network of Strength
(formerly Y-Me National Breast Cancer Organization)
http://www.networkofstrength.org
Living Beyond Breast Cancer
http://www.lbbc.org
Lymphedema Research Foundation (LRF)
http://www.lymphaticresearch.org
Lymphology Association of North America (LANA)
http://www.clt-lana.org
The Moss Report
http://www.cancerdecisions.com
National Breast Cancer Coalition
http://www.stopbreastcancer.org
National Lymphedema Network (NLN)
http://www.lymphnet.org
Sisters Network
A National African-American Breast Cancer Survivorship Organization
http://www.sistersnetworkinc.org
Susan G. Komen for the Cure
http://ww5.komen.org
Dr. Susan Love Research Foundation
http://www.dslrf.org
Young Survivor Coalition
http://www.youngsurvival.org
Commonweal Retreat Center
http://www.commonweal.org
Smith Farm Center for Healing and the Arts
http://www.smithfarmcenter.com
After Breast Cancer: Answers to the Questions You’re Afraid to Ask
By Musa Mayer
Breast Cancer: Beyond Convention
By Isaac Cohen, Debu Tripathy, and Mary Tagliaferri
Breast Implants: Everything You Need to Know, 3rd Edition.
By Nancy Bruning
Choices in Healing
By Michael Lerner
Dancing in Limbo: Making Sense of Life After Cancer
By Glenna Halvorson-Boyd and Lisa K. Hunter
Dr. Susan Love’s Breast Book, 4th Edition
By Susan Love with Karen Lindsey
The First Look
By Amelia Davis
A Safe Place: A Journal for Women with Breast Cancer
By Jennifer Pike
American Cancer Society. (2008). Cancer Facts and Figures 2008. Retrieved December 10, 2008, from http://www.cancer.org.
Amis ES, Butler PF, Applegate KE, et al. (2007). American College of Radiology White Paper on Radiation Dose in Medicine. Journal of the American College of Radiology 4:272–284.
Anders C, Carey LA. (2008). Understanding and treating triple-negative breast cancer. Oncology 22:1233–39.
Anderson WF, Jatoi I, Devesa SS. (2006). Assessing the impact of screening mammography: Breast cancer incidence and mortality rates in Connecticut (1943–2002). Breast Cancer Research and Treatment 99:333–40.
Andrieu N, Easton DJ, Chang-Claude J, et al. (2006). Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: A report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators Group. (2006). Journal of Clinical Oncology 24:3361–66.
Arena F, Barone C, DiCicco T. (2003). Use of digital infrared imaging in enhanced breast cancer detection and monitoring of the clinical response to treatment. IEEE X-Plore 2:1129–32.
Armer JM, Radina ME, Porock D, Culbertson SD. (2003). Predicting breast cancer-related lymphedema using self-reported symptoms. Nursing Research 52:370–79.
Armer JM, Stewart BR. (2005). A comparison of 4 diagnostic criteria for lymphedema in a post-breast cancer population. Lymphatic Research Biology 3:208–17.
Armer JM. (2008). Lymphedema risk for breast cancer survivors increased by obesity. Medical News Today, December 23, 2008. Retrieved January 6, 2009, from http://www.medicalnewstoday.com/articles/133691.php.
Arora N, Martins D, Ruggerio D, et al. (2008). Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer. American Journal of Surgery 196:523–26.
Badgwell BD, Giordano SH, Duan ZZ, et al. (2008). Mammography before diagnosis among women age 80 years and older with breast cancer. Journal of Clinical Oncology 26:2482–88.
Baines CJ. (2005). Are there downsides to mammography screening? Breast Journal 11 Suppl:S7-10.
Baker SG, Lichtenstein P, Kaprio J, et al. (2005). Genetic susceptibility to prostate, breast, and colorectal cancer among Nordic twins. Biometrics 61:55–63.
Bender CM, Sereika SM, Brufsky AM, et al. (2007). Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer. Menopause 14:995–98.
Berg WA, Blume JD, Cormack JB, et al. (2008). Combined screening with ultrasound alone vs. mammography alone in women at elevated risk of breast cancer. Journal of the American Medical Association 299:2151–63.
Berrington de Gonzalez A, Reeves G. (2005). Mammographic screening before age 50 years in the UK: Comparison of the radiation risks with the mortality benefits. British Journal of Cancer 93:590–96.
Bondurant S, Emster V, Herdman R, eds. (1999). Safety of silicone breast implants. Washington DC: Institute of Medicine.
Brenner DJ, Sawant SG, Hande MP, et al. (2002). Routine screening mammography: How important is the radiation-risk side of the benefit-risk equation. International Journal of Radiation Biology 78:1065–67.
Calaf GM, Hei TK. (2000). Establishment of a radiation-and-estrogen-induced breast cancer model. Carcinogenesis 21:769–76.
Cardis E, Vrijheid M, Blettner M, et al. (2005). Risk of cancer after low doses of ionizing radiation: Retrospective cohort study in 15 countries. British Medical Journal 331:77.
Carey LA, Perou CM, Livasy CA, et al. (2006). Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. Journal of the American Medical Association 295:2492–502.
Centers for Disease Control and Prevention (CDC). (2007). Decline in breast cancer incidence—United States, 1999–2003. Morbidity and Mortality Weekly Report 56: 549–53.
Centers for Disease Control and Prevention. (2005). Third national report on human exposure to environmental chemicals. Atlanta: Centers for Disease Control and Prevention.
Chaudhry A, Puntis ML, Gikas P, et al. (2006). Does the timing of breast cancer surgery in pre-menopausal women affect clinical outcome?: An update. International Seminars in Surgical Oncology 3:37 doi:10.1186/1477-7800-3-37.
Clarke M, Collins R, Darby S, et al. (2005). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet 366:2087–106.
Connor SR, Fitch K, Iwasaki K. (2007). Family evaluation of hospice care: results from voluntary submission of data via website. Journal of Pain and Symptom Management 33:238–46.
Coyle B, Polovich M. (2004). Handling hazardous drugs: How safe are you? American Journal of Nursing 104 (2):104.
Czene K, Lichtenberg P, Hemminki K. (2002). Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family cancer database. International Journal of Cancer 99 (2):260–66.
Darby S, McGale P, Taylor C, et al. (2005). Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in U.S.SEER cancer registries. Lancet Oncology 6:557–65.
Davis A. (2000). The First Look. Urbana and Chicago, IL: University of Illinois Press.
Environmental Protection Agency (EPA), Office of Pollution Prevention and Toxics. (2007). Overview: Office of Pollution and Prevention Toxics Programs. Retrieved January 14, 2009, from http://www.epa.gov/oppt/pubs/oppt101c2.pdf.
Erren TC. (2001). A meta-analysis of epidemiologic studies of electric and magnetic fields and breast cancer in women and men. Bioelectromagnetics Supplement 5:S105–19.
Evans N. (2009). Breast cancer 101: Roadmap for an unexpected journey. In press.
Farquhar C, Marjoribanks J, Basser R, et al. (2005). High-dose chemotherapy and autologous bone marrow or stem-cell transplantation vs. conventional chemotherapy for women with metastatic breast cancer. Cochrane Database System Review July 20:(3):CD003142.
Ganz PA, Desmond KA, Leedham B, et al. (2002). Quality of life in long-term, disease-free survivors of breast cancer: A follow-up study. Journal of the National Cancer Institute 94(6):463.
Giordano AE. (2008). Chapter 16, Breast.In McPhee SJ, Papadakis M, Current Medical Diagnosis and Treatment, 47th edition. New York: McGraw-Hill-Lange.
Giordano SH, Cohen DS, Buzdar AU, et al. (2004). Breast carcinoma in men: A population-based study. Cancer Online, May, 2004, (DOI:10:1002/cncr.20312).
Gotzsche PC, Hartling OJ, Nielsen M, et al. (2009). Breast screening: The facts or maybe not. British Medical Journal 338:b86. Published online January 27, 2009, doi:10.1136/bmj.b86.
Gotzsche PC, Nielsen M. (2006). Screening for breast cancer with mammography. Cochrane Database System Review 2006 (4):CD001877.
Gronwald J, Pijpe A, Byrski T, et al. (2008). Early radiation exposures and BRCA1-associated breast cancer in young women from Poland. Breast Cancer Research and Treatment 112:581–584.
Hankinson SE, Colditz GA, Willett WC. (2004). Towards an integrated model for breast cancer etiology: The lifelong interplay of genes, lifestyle, and hormones. Breast Cancer Research 6:213–18.
Houchens NW, Merajver SD. (2008). Molecular determinants of the inflammatory breast cancer phenotype. Oncology (Williston Park) 22:1556–61.
Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, et al. (2001). Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. Journal of the National Cancer Institute 6:93:824–42.
Huang J, Mackillop WJ. (2001). Increased risk of soft-tissue sarcoma after radiotherapy in women with breast carcinoma. Cancer 92:172–80.
Hurria A, Rosen C, Hudis C, et al. (2006). Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: A pilot prospective longitudinal study. Journal of the American Geriatric Society 54:925–31.
Inagaki M, Yoshikawa E, Matsuoka Y, et al. (2007). Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer 109:146–56.
Jemal A, Murray T, Ward E, et al. (2005). Cancer Statistics, 2005. CA: A Cancer Journal for Clinicians 55:10–30.
Kontos M, Fentiman IS. (2006). Perioperative endocrine status and prognosis in early breast cancer. Breast Journal 12:518–25.
Krag DN, Anderson SJ, Julian TB, et al. (2007). Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: Results from the NSABP B-32 randomised phase III trial. Lancet Oncology 8:881–88.
Kruk J, Aboul-Enein HY. (2006). Environmental exposure and other behavioral risk factors in breast cancer. Current Cancer Therapy Reviews 2:3–21.
Lawenda BD, Mondry TE, Johnstone PAS. (2009). Lymphedema: A primer on the identification and management of a chronic condition in oncologic treatment. CA: A Cancer Journal for Clinicians 59:8–24.
LeCarpentier GL, Roubidoux MA, Fowlkes JB, et al. (2008). Suspicious breast lesions: Assessment of 3D Doppler US indexes for classification in a test population and fourfold cross-validation scheme. Radiology 249:463–70.
Lord SJ, Lei W, Craft P, et al. (2007). A systematic review of the effectiveness of magnetic resonance imaging (MRI) as an addition to mammography and ultrasound in screening young women at high risk of breast cancer. European Journal of Cancer 43:1905–17.
Lerner M. (1994). Choices in Healing. Cambridge: MIT Press.
Low J, Berman A, Steinberg S, et al. (2004). Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. Journal of Clinical Oncology 22:4065–74.
Lund E, Bakken K, Dumeaux V, et al. (2007). Hormone replacement therapy and breast cancer in former users of oral contraceptives: The Norwegian women and cancer study. International Journal of Cancer 121:645–48.
McCance KL, Huether SE. (2006). Pathophysiology: The biologic basis for diseases in adults and children, 5th edition. St. Louis, MO: Mosby.
Miller AB, To T, Baines CJ, et al. (2000). Canadian national breast screening study-2: 13-year results of a randomized trial in women aged 50–59 years. Journal of the National Cancer Institute 92:1490–99.
Mitsiades N, Correa D, Gross CP, et al. (2008). Cognitive effects of hormonal therapy in older adults. Seminars in Oncology 35(6): 569–81.
Morello-Frosch, R. (1997). Rachel’s Daughters: Searching for the Causes of Breast Cancer, documentary film. Light-Saraf Films.
Moss R. (2006). Mammography, biopsy and the detection of breast cancer: A special report by Ralph W. Moss. Retrieved November 3, 2008, from http://www.cancerdecisions.com.
National Cancer Institute. (2007). Radiation therapy and you. Retrieved February 10, 2009, from http://www.cancer.gov/cancertopics/radiation-therapy-and-you/page8#SE8.
National Toxicology Program. (2005). Eleventh Report on Carcinogens. National Institute of Environmental Health Sciences. National Institutes of Health. Retrieved December 10, 2008, from http://ntp-server.niehs.nih.gov.
Newman LA. (2005). Breast cancer in African American women. The Oncologist 10:1–14.
Nickerson K. (2006). Environmental contaminants in breast milk. Journal of Midwifery and Women’s Health 51:26–54.
Northern California Cancer Center. (2008). Understanding DCIS. Retrieved January 14, 2009, from http://www.dcis.info/screening.html.
O’Toole C. (1999). My experiences in navigating the maze of complementary therapy. Innovations in Breast Cancer Care 4:121–24. West Conshohocken, PA: Meniscus Educational Institute.
Parisky YR, Sardi A, Hamm R, Hughes K, Esserman L, et al. (2003). Efficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesions. American Journal of Roentgenology 180:263–69.
Patt D, Goodwin JS, Kuo Y, Freeman JL, et al (2005). Cardiac morbidity of adjuvant radiotherapy for breast cancer. Journal of Clinical Oncology 23:7475–82.
Pezner RD, Patterson MP, Hill LR, et al. (1985). Breast edema in patients treated conservatively for stage I and II breast cancer. International Journal of Radiation Oncology, Biology and Physiology 11:1765–68.
Phillips KA, Bernhard J. (2003). Adjuvant breast cancer treatment and cognitive function: Current knowledge and research directions. Journal of the National Cancer Institute 95(3):190–97.
Qaseem A, Snow V, Sherif K, Aronson M, et al., for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians. (2007). Screening mammography for women 40 to 49 years of age: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine 146:511–15.
Raffle A, Gray M. (2007). Screening: Evidence and practice. Oxford: Oxford University Press.
Ravdin PM, Cronin KA, Howlader N, Berg CD, et al. (2007). The decrease in breast cancer incidence in the United States. New England Journal of Medicine 356:1670–74.
Recht A, Edge SB. (2003). Evidence-based indications for postmastectomy irradiation. Surgical Clinics of North America 83(4):995–1013
Roychoudhuri R, Evans H, Robinson D, Moller H. (2004). Radiation-induced malignancies following radiotherapy for breast cancer. British Journal of Cancer 91:868–72.
Rosenberg RD, Hunt WC, Williamson MR, et al. (1998). Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: Review of 183,134 screening mammograms in Albuquerque, New Mexico. Radiology 209:511–18.
Robbins A, Clarke CA. (2007). Regional changes in hormone therapy use and breast cancer incidence in California from 2001 to 2004. Journal of Clinical Oncology 25(23):3437–39.
Rosser RJ. (2000). A point of view: Trauma is the cause of occult micrometastatic breast cancer in sentinel axillary lymph nodes. Breast Journal 6:209–12.
Rudel RA, Attfield KA, Schifano JN, Brody JG. (2007). Chemicals causing mammary gland tumors in animals signal new directions for epidemiology, chemicals testing and risk assessment for breast cancer prevention. Cancer 109(12):2635–66.
Russo J, Russo I. (2004). Chapter 4, The role of estrogen in breast cancer. In Molecular Basis of Breast Cancer, Berlin: Springer-Verlag.
Sakr R, Antoine M, Barranger E, Dubernard G, Salem C, Daraï E, Uzan S. (2008). Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma. Breast Journal 14:55–60.
Segaloff A, Maxfield WS. (1971). The synergism between radiation and estrogen in the production of mammary cancer in the rat. Cancer Research 31:166–68.
Shuryak I, Sachs RK, Hlatky L, Little MP, et al. (2006). Radiation-induced leukemia at doses relevant to radiation therapy: Modeling mechanisms and estimating risks. Journal of the National Cancer Institute 98:1794–1806.
Smigal C, Jemal A, Ward E, Cokkinides V, Smith R, et al. (2006). Trends in breast cancer by race and ethnicity: Update 2006. CA: A Cancer Journal for Clinicians 56:168–83.
Smith IE, Ross GM. (2004). Breast radiotherapy after lumpectomy: No longer always necessary. New England Journal of Medicine 351:1021–23.
Smith RA, Cokkinides V, Brawley OW. (2009). Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening. CA: A Cancer Journal for Clinicians 59:27–41.
Smith RA, Saslow D, Andrews K, Burke W, et al. (2003). American Cancer Society Guidelines for Breast Cancer Screening: Update 2003. CA: A Cancer Journal for Clinicians 53:141–69.
Steingraber S. (2007). The falling age of puberty in U.S. girls: What we know, what we need to know. San Francisco: Breast Cancer Fund. Retrieved from http://www.breastcancerfund.org/puberty.
Stewart A, Collins B, Mackenzie, Tomiak E. (2008). The cognitive effects of adjuvant chemotherapy in early stage breast cancer: A prospective study. Psychooncology 17:122–30.
Teitelbaum SL, Britton JA, Gammon MD, Schoenberg JB, et al. (2003). Occupation and breast cancer in women 20–44 years of age. Cancer Causes and Control 14:627–37.
U.S. Preventive Services Task Force. (2002). Screening for breast cancer: Recommendations and rationale. Retrieved October 28, 2008, from http://www.ahrq.gov/clinic/3rduspstf/breastcancer/brcanrr.htm.
Vainio H, Bianchini F. (2002). IARC handbooks of cancer prevention. Volume 7: Breast cancer screening. Lyon: IARC Press.
Valentgas P, Daling JR, Malone KE, Weiss NS, Williams MA, Self SG, Mueller BA. (1999). Pregnancy after Breast Carcinoma: Outcomes and Influence on Mortality. Cancer 85:2424–32.
Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, et al. (2004). Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. Journal of the American Medical Association 292:1317–25.
Watmough, DJ, Quan KM, Aspden RM, Mallard JR. (1992). Study of tissue compression in breast phantoms: Possible implications for the use of X-ray mammography as a method of imaging breast carcinoma. European Journal of Surgical Oncology 18:538–44.
Weiss JR, Moysich KB, Swede H. (2005). Epidemiology of male breast cancer. Cancer Epidemiology, Biomarkers and Prevention 14:20–6.
Welch HG. (2008). The excessive focus on mammography: Looking harder to find more may not be the best practice. Los Angeles Times, November 3, 2008. Retrieved November 11, 2008, from http://www.latimes.com/news/opinion/commentary/la-oe-welch3-2008nov03,0,2369816.story.
West JG, Qureshi A, West JE, Chacon M, Sutherland ML, et al. (2005). Risk of angiosarcoma following breast conservation: A clinical alert. The Breast Journal 11:115–23.
Zuther E.Pathology. (2005). In Von Rohr M, ed. Lymphedema Management: The comprehensive guide for practitioners. New York: Thieme Medical Publishers, Inc. 45–99.
GET THE WILD IRIS NEWSLETTER!
NursingCEU.com is a division of Wild Iris Medical Education
Copyright © 1999-2010 Wild Iris Medical Education, Inc.
Photograph © 2008 Jon Klein
Get discounts, special offers, and information.
We do not sell, rent, or share our mailing list.
