carcinoma of the breast
car·ci·no·ma of the breast
[MIM*114480]Breast cancer is the most common noncutaneous malignancy in women. A woman's lifetime risk of developing breast cancer is 8%, and approximately 182,000 cases are newly diagnosed each year in the U.S. With 46,000 deaths yearly, it ranks second only to lung cancer as a cause of cancer deaths in women. Most breast cancers are estrogen-dependent adenocarcinomas. Many factors, including age, race, family history, and reproductive history, influence a woman's risk of developing breast cancer. The risk rises with advancing age: it is less than 0.1% at age 30, about 2% at age 50, and 10% at age 80. African-American women have the highest mortality and lowest survival rates for breast cancer. Asian women living in the U.S. have the lowest rates, but some studies suggest that their cancer risk increases as they become acculturated. The risk of breast cancer is slightly increased by nulliparity or first pregnancy after age 35 and by early menarche or late menopause. About 10% of breast cancers are induced by inherited genetic mutations (particularly BRCA1 and BRCA2 mutations, which together account for about one third of familial breast cancers), the rest by spontaneous, noninherited mutations. The HER-2/neu oncogene, which encodes a 185-kD transmembrane oncoprotein, is amplified, overexpressed, or both in 10-30% of invasive breast cancers and in 40-60% of intraductal breast carcinomas. Detection of this gene in cancer tissue is associated with poor prognosis (30% greater likelihood of recurrence and cancer death). Women with a strong family history of breast cancer tend to develop it at an earlier age and may also be at risk of ovarian and other malignancies. Other risk factors are cigarette smoking, daily alcohol use, exposure to environmental radon, therapeutic and diagnostic radiation including that from mammograms, and estrogen replacement therapy (with or without a progestogen). A large prospective study found that taking 2 or more 325-mg tablets of aspirin a week reduced the risk of breast cancer by about 20%, and that taking 2 or more 200-mg tablets of ibuprofen a week reduced the risk by about 50%. The possibility of identifying inherited oncogenes has generated controversy as to the appropriateness of prophylactic mastectomy for women at risk of early mammary carcinoma. Tamoxifen, an estrogen antagonist used in the treatment of estrogen-dependent breast cancer, reduces by 50% the risk of invasive cancer in women with a strong family history of breast cancer, particularly those over 40. Authorities recommend annual mammography for all women over 40, and for high-risk women (those with a strong family history of breast cancer and those who have received irradiation treatment for Hodgkin disease) over 25. Magnetic resonance imaging may detect tumors at an earlier stage than mammography, and has been recommended by some authorities for annual surveillance of women at high risk. Because some 10% of breast cancers that can be palpated on examination are missed by mammography, annual examination of the breasts by a physician is also recommended. However, studies have not shown reduction in breast cancer mortality when clinical examination is added to mammography, nor have they shown any survival advantage for women practicing breast self examination. Treatments for breast cancer include surgical excision, limited or extensive, with or without radical dissection and removal of axillary lymph nodes; irradiation; and chemotherapy, depending on the type and stage of the disease. Limited resection of small invasive tumors, with preservation of the breast, yields survival rates similar to those after modified radical mastectomy. Radiotherapy with tangentially directed beams of limited penetration can markedly reduce the rate of both local recurrence and distant metastasis after excision of breast cancer without inflicting radiation damage on the heart and great vessels. Chemotherapeutic agents in standard use include doxorubicin, epirubicin, cyclophosphamide, and paclitaxel. Trastuzumab, a monoclonal antibody to the HER-2/neu oncogene, shrinks tumors that contain that gene, but its use is associated with a high incidence of cardiac dysfunction. Estrogen-responsive tumors are treated by hemical oophorectomy with agents that limit or oppose estrogen activity, including the GnRH analogue goserelin, the estrogen antagonists tamoxifen and toremifene, the estrogen receptor antagonist fulvestrant, and the aromatase inhibitors anastrozole, letrozole, and exemestane (which inhibit nonovarian estrogen production in postmenopausal women). Known or suspected metastases from an estrogen-responsive tumor are treated with these agents or by oophorectomy. see also BRCA1 gene, BRCA2 gene, mammography, tamoxifen