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Breast Cancer Treatment (PDQ®)

Health Professional Version

General Information About Breast Cancer

This summary discusses primary epithelial breast cancers in women. The breast is rarely affected by other tumors such as lymphomas, sarcomas, or melanomas. Refer to the following PDQ summaries for more information on these cancer types:

Breast cancer also affects men and children and may occur during pregnancy, although it is rare in these populations. Refer to the following PDQ summaries for more information:

Incidence and Mortality

Estimated new cases and deaths from breast cancer (women only) in the United States in 2014:[1]

  • New cases: 232,670.
  • Deaths: 40,000.

Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 62,570 cases of in situ disease, 232,670 new cases of invasive disease, and 40,000 deaths expected in 2014.[1] Thus, fewer than one of six women diagnosed with breast cancer die of the disease. By comparison, it is estimated that about 72,330 American women will die of lung cancer in 2014.[1] Men account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section in the PDQ summary on Breast Cancer Screening for more information).

Widespread adoption of screening increases breast cancer incidence in a given population and changes the characteristics of cancers detected, with increased incidence of lower-risk cancers, premalignant lesions, and ductal carcinoma in situ (DCIS). (Refer to the Ductal Carcinoma In Situ section in the Breast Cancer Diagnosis and Pathology section in the PDQ summary on Breast Cancer Screening for more information.) Population studies from the United States [2] and the United Kingdom [3] demonstrate an increase in DCIS and invasive breast cancer incidence since the 1970s, attributable to the widespread adoption of both postmenopausal hormone therapy and screening mammography. In the last decade, women have refrained from using postmenopausal hormones, and breast cancer incidence has declined, but not to the levels seen before the widespread use of screening mammography.[4]

Anatomy

Drawing of female breast anatomy showing the lymph nodes, nipple, areola, chest wall, ribs, muscle, fatty tissue, lobe, ducts, and lobules.
Anatomy of the female breast. The nipple and areola are shown on the outside of the breast. The lymph nodes, lobes, lobules, ducts, and other parts of the inside of the breast are also shown.

Risk and Protective Factors

Increasing age is the most important risk factor for breast cancer.[2] Other risk factors for breast cancer include the following:

  • Family health history.[5]
  • Major inheritance susceptibility.[6-8]
    • Germline mutation of the genes BRCA1 and BRCA2, and other breast cancer susceptibility genes.[9-13]
  • Alcohol intake.[14]
  • Breast tissue density (mammographic).[15,16]
  • Estrogen (endogenous):[17-20]
    • Menstrual history (early menarche/late menopause).[21-23]
    • Nulliparity.
    • Older age at first birth.
  • Hormone therapy history:[24]
    • Combination estrogen plus progestin hormone replacement therapy (HRT).[25-28]
    • Oral contraception.[29]
  • Obesity.[30,31]
  • Lack of physical exercise.[32]
  • Personal history of breast cancer.[33]
  • Personal history of proliferative forms of benign breast disease.[34-40]
  • Race.[41,42]
  • Radiation exposure to the breast/chest.[43,44]

Age-specific risk estimates are available to help counsel and design screening strategies for women with a family history of breast cancer.[45,46]

Of all women with breast cancer, 5% to 10% may have a germline mutation of the genes BRCA1 and BRCA2.[47] Specific mutations of BRCA1 and BRCA2 are more common in women of Jewish ancestry.[48] 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 high as 5% per year.[49] Male BRCA2 mutation carriers also have an increased risk of breast cancer.[50]

Mutations in either the BRCA1 or the BRCA2 gene also confer an increased risk of ovarian cancer [50,51] or other primary cancers.[50,51] Once a BRCA1 or BRCA2 mutation has been identified, other family members can be referred for genetic counseling and testing.[52-55] (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers; Breast Cancer Prevention; and Breast Cancer Screening for more information.)

(Refer to the PDQ summary on Breast Cancer Prevention for more information about factors that increase the risk of breast cancer.)

Protective factors and interventions to reduce the risk of female breast cancer include the following:

  • Estrogen use (after hysterectomy).[56-58]
  • Exercise.[59-61]
  • Early pregnancy.[23,62,63]
  • Breast feeding.[64]
  • Selective estrogen receptor modulators (SERMs).[65]
  • Aromatase inhibitors or inactivators.[66,67]
  • Risk-reducing mastectomy.[68]
  • Risk-reducing oophorectomy or ovarian ablation.[69-72]

(Refer to the PDQ summary on Breast Cancer Prevention for more information about factors that decrease the risk of breast cancer.)

Screening

Clinical trials have established that screening asymptomatic women using mammography, with or without clinical breast examination, decreases breast cancer mortality. (Refer to the PDQ summary on Breast Cancer Screening for more information.)

Diagnosis

Patient evaluation

When breast cancer is suspected, patient management generally includes the following:

  • Confirmation of the diagnosis.
  • Evaluation of the stage of disease.
  • Selection of therapy.

The following tests and procedures are used to diagnose breast cancer:

  • Mammography.
  • Ultrasound.
  • Breast magnetic resonance imaging (MRI), if clinically indicated.
  • Biopsy.

Contralateral disease

Pathologically, breast cancer can be a multicentric and bilateral disease. Bilateral disease is somewhat more common in patients with infiltrating lobular carcinoma. At 10 years after diagnosis, the risk of a primary breast cancer in the contralateral breast ranges from 3% to 10%, although endocrine therapy decreases that risk.[73-75] The development of a contralateral breast cancer is associated with an increased risk of distant recurrence.[76] When BRCA1/BRCA2 mutation carriers were diagnosed before age 40 years, the risk of a contralateral breast cancer reached nearly 50% in the ensuing 25 years.[77,78]

Patients who have breast cancer will undergo bilateral mammography at the time of diagnosis to rule out synchronous disease. To detect either recurrence in the ipsilateral breast in patients treated with breast-conserving surgery or a second primary cancer in the contralateral breast, patients will continue to have regular breast physical examinations and mammograms.

The role of MRI in screening the contralateral breast and monitoring women treated with breast-conserving therapy continues to evolve. Because an increased detection rate of mammographically occult disease has been demonstrated, the selective use of MRI for additional screening is occurring more frequently despite the absence of randomized, controlled data. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation before treatment is recommended. Whether this increased detection rate will translate into improved treatment outcome is unknown.[79-81]

Prognostic Factors

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 following clinical and pathology features (based on conventional histology and immunohistochemistry):[82]

  • The menopausal status of the patient.
  • The stage of the disease.
  • The grade of the primary tumor.
  • The estrogen receptor (ER) and progesterone receptor (PR) status of the tumor.
  • Human epidermal growth factor type 2 receptor (HER2/neu) overexpression and/or amplification.
  • The histologic type. 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 carcinomas.[83-85]

The use of molecular profiling in breast cancer includes the following:[86]

  • ER and PR status testing.
  • HER2/neu receptor status testing.
  • Gene profile testing by microarray assay or reverse transcription-polymerase chain reaction (e.g., MammaPrint, Oncotype DX).

On the basis of these results, breast cancer is classified as:

  • Hormone-receptor positive.
  • HER2 positive.
  • Triple negative (ER, PR, and Her2/neu negative).

Although certain rare inherited mutations, such as those of BRCA1 and BRCA2, predispose women to develop breast cancer, prognostic data on BRCA1/BRCA2 mutation carriers who have developed breast cancer are conflicting; these women are at greater risk of developing contralateral breast cancer.

Posttherapy Considerations

Hormone replacement therapy

After careful consideration, patients with severe symptoms may be treated with hormone replacement therapy. For more information, refer to the following PDQ summaries:

Follow-up

The frequency of follow-up and the appropriateness of screening tests after the completion of primary treatment for stage I, stage II, or stage III breast cancer remain controversial.

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 with routine physical examinations.[87-89] Even when these tests permit earlier detection of recurrent disease, patient survival is unaffected.[88] On the basis of these data, acceptable follow-up can be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stages I to III breast cancer.

Related Summaries

Other PDQ summaries containing information related to breast cancer include the following:

References

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  • Updated: December 3, 2014