Breast Cancer---1

Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic lump discovered during examination or screening mammography. Diagnosis is confirmed by biopsy. Treatment usually includes surgical excision, often with radiation therapy and adjuvant systemic therapy.

About 203,000 new cases were identified in 2003. It is the 2nd leading cause of cancer death in women (after lung cancer), with about 40,000 deaths in 2003. Male breast cancer accounts for < 1% of total cases; manifestations, diagnosis, and management are the same, although men tend to present later.

Risk Factors

In the US, cumulative risk of developing breast cancer is 12% (1 in 8) by age 95, and risk of dying of it is about 4%. Much of the risk is incurred after age 60 (see Table 1: Breast Disorders: Breast Cancer Risks). These statistics can be misleading because cumulative risk of developing the cancer in any 20-yr period is considerably lower.

Family history of breast cancer in a 1st-degree relative (mother, sister, daughter) doubles or triples risk of developing the cancer, but history in more distant relatives increases risk only slightly. When ≥ 2 1st-degree relatives have breast cancer, risk may be 5 to 6 times higher. About 5% of women with breast cancer carry a mutation in one of the 2 known breast cancer genes, BRCA1 or BRCA2. If relatives of such a woman also carry the gene, they have a 50 to 85% lifetime risk of developing breast cancer. Women with BRCA1 mutations also have a 20 to 40% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is increased less. Women without a family history of breast cancer in at least 2 1st-degree relatives are unlikely to carry this gene and thus do not require screening for BRCA1 and BRCA2 mutations. Men who carry a BRCA2 mutation also have an increased risk of developing breast cancer. The genes are more common among Ashkenazi Jews.

History of in situ or invasive breast cancer increases risk: Risk of developing cancer in the contralateral breast after mastectomy is about 0.5 to 1%/yr of follow-up.

Early menarche, late menopause, or late 1st pregnancy increases risk. Women who have a 1st pregnancy after age 30 are at higher risk than those who are nulliparous.

History of fibrocystic changes requiring biopsy for diagnosis increases risk slightly. Women with multiple breast lumps but no histologic confirmation of a high-risk pattern should not be considered at high risk. Benign lesions that may slightly increase risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia (with or without atypia), sclerosing adenosis, and papilloma. Atypical ductal or lobular hyperplasia increases risk of breast cancer 4- to 5-fold; risk increases to about 10-fold in patients who also have a family history of invasive breast cancer in a 1st-degree relative.

Oral contraceptive use increases risk very slightly (by about 5 more cases per 100,000 women). Risk increases primarily during the years of contraceptive use and tapers off during the 10 yr after stopping. Risk is highest in women who began to use contraceptives before age 20 (although absolute risk is still very low).

Postmenopausal hormone (estrogen plus a progestin) therapy appears to increase risk modestly after only 3 yr of use. With prolonged use, risk is increased by about 7 or 8 cases per 10,000 women for each year of use. Use of estrogen alone does not appear to increase risk of breast cancer. Selective estrogen-receptor modulators (eg, raloxifene) may reduce risk of developing breast cancer.

Diet may play a role in causing or promoting growth of breast cancers, but conclusive evidence about the effect of a particular diet (eg, one high in fats) is lacking. Obese postmenopausal women are at increased risk, but there is no evidence that dietary modification decreases risk. For obese women who are still menstruating, risk may be decreased.

Exposure to radiation therapy before age 30 increases risk. Mantle-field radiation therapy for Hodgkin lymphoma quadruples risk of breast cancer over the next 20 to 30 yr.