Breast Cancer
Carol D. Riley
I. Definition
A. Incidence: Excluding skin cancers, breast cancer is the most common cancer in women, accounting for 32% of all cancers in the United States. In 2003, there will be an estimated 211,000 new breast cancers diagnosed. It is second only to lung cancer as the leading cause of death in women. In the United States, a woman has a 1 in 8 risk of developing breast cancer during her lifetime, with an increasing risk in each decade of life after age 40. Worldwide, breast cancer is the leading cause of cancer death among women. The overall incidence of breast cancer in Japan is approximately one fifth that of the United States. In Western Europe, 1 in 15 will develop breast cancer in their lifetime. An increase in the incidence of early breast cancer is attributed to screening and detection.
B. Epidemiology: The incidence of breast cancer is highest in developed countries. Within the United States, breast cancer is most common in Caucasian women, followed by African-American women. Asians and Hispanics are at lower risk, and American Indian women are least likely to have breast cancer.
C. Morbidity and Mortality: Although the overall incidence of breast cancer has increased, the mortality rate from breast cancer has undergone a gradual decline. This decline in mortality is likely due to numerous factors, including earlier stage at diagnosis, advances in local therapy, and advances in systemic treatment of breast cancer.
II. Etiology
A. Risk Factors: The cause of breast cancer in humans is not known, but some factors will put a woman at a higher risk than average.
1. Gender: Breast cancer occurs almost 100 times more frequently in women than in men.
2. Age: The risk of breast cancer increases with age.
3. Demographic/social factors: More commonly a disease of the upper socioeconomic classes.
4. Family history: The risk of breast cancer doubles if there is a history of breast cancer in a first-degree relative. BRCA1 and BRCA2 mutations account for only 5% to 6% of all breast cancers. Mutations of the p53 tumor-suppressor gene may contribute to 1% of breast cancers in women less than 40 years of age. Having a BRCA1 mutation gives a woman up to an 85% risk of developing breast cancer. In addition, it increases a woman’s risk of developing ovarian cancer. Having a BRCA2 mutation predisposes men to breast cancer (see Chapter 2).
5. Personal history of breast cancer, atypical hyperplasia, ductal or lobular cancer in situ increases a woman’s risk of developing primary breast cancer or a second breast cancer.
6. Reproductive factors: Nulliparity or having first full-term pregnancy after age 30 increases a women’s risk of developing breast cancer, particularly in the months after delivery.
7. Menstrual factors: Menarche before the age of 12 or onset of menopause after age 55.
8. Oral contraceptives: A recent study by Marchbanks and associates (2002) shows no association between past or present use of oral contraceptives and breast cancer risk.
9. Estrogen/progestin replacement therapy: On May 31, 2002, after a mean follow-up of 5.2 years, the Women’s Health Initiative trial, which was looking at estrogen and progestin in postmenopausal women, stopped the trial because of patient safety. Among others, the risk of breast cancer risk was increased by 26%. The absolute risk was 38 versus 30 per 10,000. This trial, however, does not address the risk of estrogen alone on the incidence of breast cancer (Rossouw et al., 2002).
10. Dietary factors: Research does not support an association between breast cancer and dietary fat intake. The use of alcohol has also been studied, and there seems to be an association between breast cancer risk and alcohol. The American Cancer Society recommends that women consume no more than one alcoholic beverage per day.
11. Exposure to radiation: There is an association between radiation exposure and breast cancer risk. The risk is inversely correlated with age, and it is very low if the exposure occurred after the age of 40. Most epidemiologic evidence is derived for women who received mantle radiation for Hodgkin’s disease at a young age.
III. Patient Management
A. Risk Reduction: There is no prevention for breast cancer, but there are ways to reduce one’s risk. The Gail model (Gail et al., 1999) is often used to identify the potential risk of breast cancer and evaluate eligibility for chemoprevention.
1. Chemoprevention. The largest breast cancer prevention trial, NSABP-P1, showed a decrease in the development of breast cancer by almost 50% in women in the tamoxifen treatment arm as compared with those receiving placebo (Fisher, 1998). Women at a high risk for breast cancer should be considered for tamoxifen prevention.
2. A newer medication, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. Raloxifene is approved to treat and prevent osteoporosis. The NSABP-P2 trial, the Study of Tamoxifen Against Raloxifene (STAR), will evaluate the efficacy of raloxifene in preventing breast cancer in high-risk women and will compare its efficacy with that of tamoxifen. Side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding serum lipids and incidence of osteoporotic bone fractures will be carefully assessed.
B. Assessment: Screening and Early Detection: The goal of screening is to detect cancers at the earliest stage possible, because the extent of disease at diagnosis is correlated with survival.
1. Screening: The American Cancer Society recommends the following:
a. Breast self-examination (BSE) should be practiced monthly by women, beginning in adolescence.
b. A skilled health care professional should provide annual clinical breast examination (CBE). The CBE should be conducted close to and preferably before the scheduled mammogram.
c. Annual mammography beginning at age 40.
2. Signs/symptoms
a. Breast cancer is found more frequently on the left side in the upper outer quadrant of the breast. The mass may be tender or painless.
b. Features suggestive of a malignant mass include:
(1) Hard, painless mass that may be fixed to the chest wall.
(2) Nipple discharge that is unilateral and serosanguineous results from a local lesion. Palpating each quadrant with one finger and observing when the discharge occurs from the duct can identify the involved quadrant.
(3) Skin dimpling and retraction. Dimpling may look like the surface of a golf ball, and retraction alters the contour of the breast. Recent onset of nipple inversion may also result from tumor growth.
(4) Redness, heat, tenderness, and edema are characteristic signs of inflammatory breast cancer that result from dermal involvement.
(5) Skin ulceration is often present with locally advanced carcinoma.
(6) Nipple changes may be moist, eczematous, dry, or psoriatic in Paget’s disease of the nipple.
(7) Peau d’orange skin changes appear as thickened skin with prominent pores. It is the result of obstructed lymphatic drainage.
(8) Palpable lymph nodes are frequently an indication of metastasis. They are most commonly palpable in the axilla, but supraclavicular, infraclavicular, inframammary, or cervical lymph nodes may also be enlarged.
C. Diagnosis
1. Radiology
a. Mammography
(1) Mammography is useful in screening asymptomatic women, evaluating palpable masses, and monitoring women who are at high risk for breast cancer. This small dose of radiation is best able to penetrate the tissue of women who are postmenopausal, over 50 years of age, and have less dense breast tissue.
(2) All patients with any clinically worrisome breast mass should undergo mammography, and all palpable breast masses that cannot be definitely ruled benign should be biopsied.
(3) Dense tissue, scar tissue, or breast implants can impede visualization.
(4) Mammography findings suggestive of malignancy include an irregular or spiculated mass, clustered calcifications, solid
nodule with ill-defined borders, architectural distortion, or a focal density.
nodule with ill-defined borders, architectural distortion, or a focal density.
b. Ultrasound, although not approved for screening, is useful in diagnosing a breast mass in young women with dense tissue. It is often used as an adjunct to mammography and is helpful in differentiating solid masses from cysts.
c. Magnetic resonance imaging (MRI) is investigational for screening. It is more expensive but improves the sensitivity and specificity of mammography. It differentiates between solid and liquid tumors of small size. It may be the best method of visualization for women with silicone implants.
d. Positron emission tomography (PET) is being studied and is not proven for screening. It is adjunctive to mammography in patients with dense breasts. It may also be useful in patients with axillary or internal mammary lymph nodes.
2. Biopsy: Tissue is necessary to make a diagnosis of breast cancer.
a. Fine-needle aspiration (FNA) is used most often to differentiate between solid and cystic masses. It is inexpensive, causes little discomfort, and can be performed in an outpatient or office setting. It cannot, however, distinguish between invasive cancers and a ductal carcinoma in situ (DCIS)
b. Core-needle biopsy can be done with or without the assistance of ultrasound. It is appropriate for both palpable and nonpalpable breast masses and will yield enough tissue to adequately evaluate the tissue for immunohistochemistry (ie, hormone receptors [HR] and HER2/neu status). It is highly accurate and can be performed in an office or outpatient setting.
c. Stereotactic biopsy is useful in sampling small, nonpalpable lesions, but shares the same limitations as FNA.
d. Open biopsy may be required for some lesions to determine a definitive diagnosis. This is done in the operating room, is more expensive, and requires a longer period of recovery. The biopsy may be incisional, sampling only part of the tumor, or excisional, removing the total tumor.
D. Treatment
1. Staging: The American Joint Committee on Cancer (AJCC, 2002) recently developed a new staging system to take into account number of lymph nodes and micrometastasis (Table 10-1). This new system also reclassifies internal mammary nodes and infraclavicular nodes (Table 10-2).
2. Treatment plan: The treatment of breast cancer varies according to type, stage, and hormone sensitivity. The three modalities of treatment include surgery, radiation, and systemic drug therapy.
a. Surgery—Two major types of surgery are used: mastectomy and breast-conserving therapy, with or without lymph node dissection and/or sentinel node biopsy. The goal of surgery is to remove the existing tumor as well as to determine staging and prognostic information. Surgery is used primarily with early-stage breast cancer when the goal of therapy is cure. It is also used for palliation in the metastatic setting when there is a large breast mass that is ulcerating and painful.
TABLE 10-1 Definition of TNM | ||||||||||||||||||||||||||||||||||||||||||
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(1) Breast-conserving therapy (lumpectomy) is a limited removal of the tumor and a margin of normal tissue while leaving much of the breast intact. Radiation therapy is required to complete local treatment. Lumpectomy may be a choice for women without multifocal disease who have adequate tissue for good cosmesis.
(2) Mastectomy is the removal of the entire breast. This is most often performed in women who have large tumors or multifocal disease or who are not otherwise candidates for breast-conserving therapy. This is also performed based on patient preference. Immediate or delayed reconstruction is an option for these patients.
(3) Exploration of the axillary nodes is necessary in patients with invasive breast cancers. Node dissection determines staging
and guides physicians in treatment recommendations. In the past, a full axillary node dissection was performed; more recently, however, the sentinel node biopsy is being studied as an alternative. The sentinel lymph node is the first node to receive drainage from the breast and more likely to contain metastatic cancer cells. It is identified through visualization of blue dye injected at the tumor site and intraoperative gamma probe detection. If the sentinel node is identified, patients may avoid a full axillary dissection if the sentinel node is free of cancer cells. Sentinel node biopsy is not the standard of care. There is a learning curve associated with this technique, and there is a 9% to 15% false-negative rate. Ongoing studies are evaluating the use of sentinel lymph node dissection alone as adequate and reliable for staging.
and guides physicians in treatment recommendations. In the past, a full axillary node dissection was performed; more recently, however, the sentinel node biopsy is being studied as an alternative. The sentinel lymph node is the first node to receive drainage from the breast and more likely to contain metastatic cancer cells. It is identified through visualization of blue dye injected at the tumor site and intraoperative gamma probe detection. If the sentinel node is identified, patients may avoid a full axillary dissection if the sentinel node is free of cancer cells. Sentinel node biopsy is not the standard of care. There is a learning curve associated with this technique, and there is a 9% to 15% false-negative rate. Ongoing studies are evaluating the use of sentinel lymph node dissection alone as adequate and reliable for staging.
TABLE 10-2 Stage Grouping | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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b. Radiation therapy
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