- Risk factors include delayed childbearing, positive family history of breast cancer or genetic mutations (BRCA1, BRCA2), and personal history of breast cancer or some types of mammary dysplasia.
- Most women with breast cancer do not have identifiable risk factors.
- Early findings: Single, nontender, firm to hard mass with ill-defined margins; mammographic abnormalities and no palpable mass.
- Later findings: Skin or nipple retraction; axillary lymphadenopathy; breast enlargement, redness, edema, pain; fixation of mass to skin or chest wall.
Incidence & Risk Factors
Next to skin cancer, breast cancer is the most common type of cancer in women, second only to lung cancer as a cause of death. The probability of developing breast cancer increases throughout life. The mean and the median age of women with breast cancer is between 60 and 61 years.
There will be about 211,240 new cases of breast cancer and about 40,410 deaths from this disease in women in the United States in the year 2005. An additional 59,000 cases of ductal carcinoma in situ will be detected, principally by screening mammography. One out of every eight or nine American women will develop breast cancer during her lifetime. The incidence of breast cancer continues to increase, but recently mortality has appeared to decrease slightly. This reflects both early detection and increased use of systemic therapy. Women whose mothers or sisters had breast cancer are three to four times more likely to develop the disease. Risk is further increased in patients whose mothers’ or sisters’ breast cancers occurred before menopause or were bilateral and in those with a family history of breast cancer in two or more first-degree relatives. However, there is no history of breast cancer among female relatives in over 75% of patients. Nulliparous women and women whose first full-term pregnancy was after age 35 have a 1.5 times higher incidence of breast cancer than multiparous women. Late menarche and artificial menopause are associated with a lower incidence, whereas early menarche (under age 12) and late natural menopause (after age 50) are associated with a slight increase in risk. Fibrocystic condition, when accompanied by proliferative changes, papillomatosis, or atypical epithelial hyperplasia, is associated with an increased incidence. A woman who has had cancer in one breast is at increased risk of developing cancer in the other breast. Such women develop a contralateral cancer at the rate of 1% or 2% per year. Women with cancer of the uterine corpus have a risk of breast cancer significantly higher than that of the general population, and women with breast cancer have a comparably increased risk for endometrial cancer. In the United States, breast cancer is more common in whites. The incidence of the disease among nonwhites (mostly blacks) is increasing, especially in younger women. In general, rates reported from developing countries are low, whereas rates are high in developed countries, with the notable exception of Japan. Some of the variability may be due to underreporting in the developing countries, but a real difference probably exists. Dietary factors, particularly increased fat consumption, may account for some differences in incidence. Oral contraceptives do not appear to increase the risk of breast cancer. There is evidence that administration of estrogens to postmenopausal women may result in a slightly increased risk of breast cancer, but only with higher, long-term doses of estrogens. Concomitant administration of progesterone and estrogen may markedly increase the incidence of breast cancer compared with the use of estrogen alone. The Women’s Health Initiative prospective randomized study of hormone replacement therapy stopped treatment with estrogen and progesterone early because of an increased risk of breast cancer compared with untreated controls or women treated with estrogen alone. Alcohol consumption increases the risk slightly. Some inherited breast cancers have been found to be associated with a gene on chromosome 17. This gene, BRCA1, is mutated in families with early-onset breast cancer and ovarian cancer. As many as 85% of women with BRCA1 gene mutations will develop breast cancer in their lifetime. Other genes are associated with increased risk of breast and other cancers, such as BRCA2, ataxia-telangiectasia mutation, and p53, the tumor suppressor gene. p53 mutations have been found in approximately 1% of breast cancers in women under 40 years of age. Genetic testing is now commercially available for women at high risk of breast cancer. Women with genetic mutations who develop breast cancer may be treated in the same way as women who do not have mutations (ie, lumpectomy), though data are emerging to suggest an increased recurrence rate for these women. Such women with mutations often elect bilateral mastectomy as treatment. Some states have enacted legislation to prevent insurance companies from considering mutations as “preexisting conditions,” preventing insurability.
Women at greater than normal risk of developing breast cancer (
Table 17-1) should be identified by their physicians, taught the techniques of breast self-examination, and followed up carefully. Those with an exceptional family history should be counseled and given the option of genetic testing. Some of these high-risk women may consider prophylactic mastectomy or tamoxifen.
The National Surgical Adjuvant Breast Project (NSABP) conducted the Breast Cancer Prevention Trial (BCPT), which studied the efficacy of tamoxifen as a preventive agent in women who had never had breast cancer but were at high risk for developing the disease. Women who received tamoxifen for 5 years had about a 50% reduction in noninvasive and invasive cancers compared with women taking placebo. However, women above the age of 50 years who received the drug had an increased incidence of endometrial cancer and deep vein thrombosis. Unfortunately, no survival data will be produced from this trial. The selective estrogen receptor modulator (SERM) raloxifene, effective in preventing osteoporosis, has also shown some promise in preventing breast cancer. This, however, requires further investigation. Several large studies examining this hypothesis are under way. Recently, considerable data have become available regarding the efficacy and success of using aromatase inhibitors to treat breast cancer. Based upon this compelling body of evidence, large multicenter studies (International Breast Cancer Intervention Study II [IBIS-II] and MAP-3) of aromatase inhibitors to prevent breast cancer are currently under way.
- Bening Breast Disorders
- Fibrocystic Condition
- Fibroadenoma of the Breast
- Nipple Discharge
- Fat Necrosis
- Breast Abscess
- Disorders of the Augmented Breast
- Carcinoma of the Female Breast
- Essentials of Diagnosis
- Incidence & Risk Factors
- Early Detection of Breast Cancer
- Differential Diagnosis
- Pathologic types
- Special Clinical Forms of Breast Cancer
- Curative Treatment
- Palliative Treatment
- Follow-Up Care
- Carcinoma of the Male Breast
Andrews L et al: Psychological impact of genetic testing for breast cancer susceptibility in women of Ashkenazi Jewish background: a prospective study. Genet Test 2004;8:240. Pubmed: 15727246
Colditz GA: Estrogen, estrogen plus progestin therapy, and risk of breast cancer. Clin Cancer Res 2005;11(2 Pt 2):909s.
Cuzick J: Aromatase inhibitors for breast cancer prevention. J Clin Oncol 2005;23:1636. Pubmed: 15755971
Dite GS et al: Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst 2003;95:448. Pubmed: 12644538
Ettinger B et al: Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637. Pubmed: 10517716
Euhus DM: Understanding mathematical models for breast cancer risk assessment and counseling. Breast J 2001;7:224. Pubmed: 11678799
Fabian CJ et al: Selective estrogen-receptor modulators for primary prevention of breast cancer. J Clin Oncol 2005;23:1644. Pubmed: 15755972
Freedman AN et al: Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J Natl Cancer Inst 2003;95:526. Pubmed: 12671020
Jemal A et al: Cancer Statistics, 2005. CA Cancer J Clin 2005;55:10. Pubmed: 15661684
King MC et al: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 2001;286:2251.
Narod SA et al: Prevention and management of hereditary breast cancer. J Clin Oncol 2005;23:1656. Pubmed: 15755973
Narod SA et al: Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002;94:1773. Pubmed: 12464649
Rebbeck TR et al: Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2004;22:1055. Pubmed: 14981104
Rossouw JE et al: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321. Pubmed: 12117397
Scott CL et al: Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics. Hum Genet 2003;112:542. Pubmed: 12601471
Wrensch MR et al: Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid. J Natl Cancer Inst 2001;93:1791. Pubmed: 11734595
Revision date: July 4, 2011
Last revised: by Sebastian Scheller, MD, ScD