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Breast Cancer Treatment

Estimated new cases and deaths from breast cancer (women only) in the United States in 2007:

* New cases: 178,480.
* Deaths: 40,460.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy.

Several well-established factors have been associated with an increased risk of breast cancer. These include family history, nulliparity, early menarche, advanced age, and a personal history of breast cancer (in situ or invasive).

Clinical trials have established that screening with mammography, with or without clinical breast examination, may decrease breast cancer mortality. (Refer to the PDQ summary on Screening for Breast Cancer for more information.) Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy may be influenced by the age and menopausal status of the patient, stage of the disease, histologic and nuclear grade of the primary tumor, estrogen-receptor (ER) and progesterone-receptor (PR) status, measures of proliferative capacity, and HER2/neu gene amplification. Although certain rare inherited mutations, such as those of BRCA1 and BRCA2, predispose women to develop breast cancer, prognostic data on mutation carriers who have developed breast cancer are conflicting. Since criteria for menopausal status vary widely, some studies have substituted age older than 50 years as a surrogate for the postmenopausal state. Breast cancer is classified into a variety of histologic types, some of which have prognostic importance. For example, favorable histologic types include mucinous, medullary, and tubular carcinoma. This section will discuss only primary epithelial breast cancers. Rarely, the breast may be involved by other tumors such as lymphoma, sarcoma, or melanoma. (Refer to the PDQ summaries on Adult Hodgkin Lymphoma, Adult Soft Tissue Sarcoma, and Melanoma for more information.)

Patient Evaluation

Patient management following initial suspicion of breast cancer generally includes confirmation of the diagnosis, evaluation of stage of disease, and selection of therapy. At the time the tumor tissue is surgically removed, ER and PR status should be determined.

Contralateral Disease

Pathologically, breast cancer can be a multicentric and bilateral disease. Bilateral disease is somewhat more common in patients with infiltrating lobular carcinoma. Patients who have breast cancer should have bilateral mammography at the time of diagnosis to rule out synchronous disease. The role of magnetic resonance imaging (MRI) in screening and follow-up continues to evolve. Having demonstrated an increased detection rate of mammographically occult disease, the selective use of MRI for additional screening is being suggested. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation prior to treatment action is recommended. Whether this increased detection rate will translate into improved treatment outcome is unknown. Patients should continue to have regular breast physical examinations and mammography to detect either recurrence in the ipsilateral breast in those patients treated with breast-conserving surgery or a second primary cancer in the contralateral breast. The risk of a primary breast cancer in the contralateral breast is approximately 1% per year. Patient age younger than 55 years at the time of diagnosis or lobular tumor histology appear to increase this risk to 1.5%. The development of a contralateral breast cancer is associated with an increased risk of distant recurrence.

Hormone Replacement Therapy

The use of hormone replacement therapy (HRT) poses a dilemma for the rising numbers of breast cancer survivors, many of whom enter menopause prematurely as a result of therapy. HRT has generally not been used for women with a history of breast cancer because estrogen is a growth factor for most breast cancer cells in the laboratory; however, empiric data on the safety of HRT after breast cancer are limited. Two randomized trials comparing HRT with no hormonal supplementation have been reported. The first trial included 345 evaluable breast cancer patients with menopausal symptoms and was terminated early because of an increased incidence of recurrences and new primaries in the HRT group (hazard ratio [HR] = 3.5; 95% confidence interval [CI], 1.5–7.4.] [Level of evidence: 1iiDi] In total, 26 women in the HRT group and 7 in the non-HRT group developed recurrences or new primaries. This study, however, was not double blinded, and it is possible that patients on HRT were monitored more closely. Because of the results of the first trial, the second trial, which was conducted under a joint steering committee with the first, closed prematurely after the enrollment of 378 patients. With a median follow-up of 4.1 years, there were 11 recurrences in the hormone replacement group and 13 recurrences in the patients assigned to no hormone replacement (HR = 0.82; 95% CI, 0.35–1.9). The trials differed in several ways; however, until further data become available, decisions concerning the use of HRT in patients with breast cancer will have to be based on the results of these studies and on inferences from the impact of HRT use on breast cancer risk in other settings. A comprehensive intervention, including education, counseling, and nonhormonal drug therapy, has been shown to reduce menopausal symptoms and to improve sexual functioning in breast cancer survivors.

Genetics

Women with a family history of breast cancer may have an increased risk of disease. Age-specific risk estimates are available to help counsel and design screening strategies for these women. Of all women with breast cancer, 5% to 10% may have a germ-line mutation of the genes, BRCA1 and BRCA2. Specific mutations of BRCA1 and BRCA2 are more common in women of Jewish ancestry. The estimated lifetime risk of developing breast cancer for women with BRCA1 and BRCA2 mutations is 40% to 85%. Carriers with a history of breast cancer have an increased risk of contralateral disease that may be as great as 5% per year. Male carriers of BRCA2 mutations are also at increased risk for breast cancer. Mutations in either gene also confer an increased risk of ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling.

Follow-up

Evidence from randomized trials indicates that periodic follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations. Even when these tests permit earlier detection of recurrent disease, patient survival is unaffected. Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer. The frequency of follow-up and the appropriateness of screening tests after the completion of primary treatment for stage I to stage III breast cancer remain controversial.

Breast Reconstruction

For patients who opt for a total mastectomy, reconstructive surgery may be used at the time of the mastectomy (immediate reconstruction) or at some subsequent time (delayed reconstruction). Breast contour can be restored by the submuscular insertion of an artificial implant (saline-filled) or a rectus muscle or other flap. If a saline implant is used, a tissue expander can be inserted beneath the pectoral muscle. Saline is injected into the expander to stretch the tissues for a period of weeks or months until the desired volume is obtained. The tissue expander is replaced by a permanent implant. (Visit the FDA's Web site for more information on breast implants.) Rectus muscle flaps require a considerably more complicated and prolonged operative procedure, and blood transfusions may be required. Following breast reconstruction, radiation therapy can be delivered to the chest wall and regional nodes either in the adjuvant setting or if local disease recurs. Radiation therapy following reconstruction with a breast prosthesis may affect cosmesis, and the incidence of capsular fibrosis, pain, or the need for implant removal may be increased.

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