One of nine women in the United States will develop breast cancer in her lifetime; a third of these women will succumb to the disease resulting in more than 44,000 death each year. Understandably, then breast cancer has received a great deal of appropriate publicity and has been the focus of intensive study relative to its origins, diagnostic methods, and treatment. Much has been gained particularly in early diagnosis and after remaining stable for many decades, the mortality rate from breast cancer in white women in the United States decreased slightly between 1989 and 1992. Unfortunately, the mortality rate for black women increased during the same period. It is both ironic and tragic that a neoplasm arising in an exposed organ readily accessible to sself examination and clinical diagnosis, continues to exact such a heavy toll, second only to lung cancer among women.

Cancer of the female breast is rarely found before the age of 25 years except in certain familial cases. The incidence then increases with age from 1 in 232 in the fourth decade to 1 in 29 in the seventh decade. The overall incidence of breast cancer in the population increased steadily up to 1988 but has been stable since that time.

Few cancers have been subjected to more intensive epidemiologic study. Observations bearing on the incidence of this disease can be summarized as follows.

Genetic predisposition

A family history is a risk factor for the development of breast cancer, and 5% to 10% of breast cancer is attributable to inheritance of an autosomal dominant gene.The probablity of genetic inheritance in creases if there are multiple affected relatives and the cancers occur at young ages. Two genes, BRCAI and BRCA2 account for the majority of hereditary breast cancers. However, less than 20% of women with a family history of breast cancer will carry these genes. Genetic susceptibility due to other genes is much less common. Breast cancer affects the majority of women with the Li-Fraumeni syndrome is associated with germ line mutations of the tumor suppressor gene p53. Women with Cowden disease have 30% to 50% risk of breast cancer by age 50 years and heterozygous carriers for ataxia telangiectasia have an 11% risk at the same age.

Although the overall incidence of breast cancer is lower in black women, women in this group present at a more advanced stage and have an increased mortality rate compared with white women. Social factors such as decreased access to health caare and lower use of mammography account for some of the difference, but genetic factors may also play a role. A greater number of breast cancers are diagnosed in young black women than in white women younger than 40 years and breast carcinomas in black women have a higher nuclear grade more frequently lack hormone receptors, and have different types of sporadic p53 mutations.

Increasing Age

Breast cancer is uncommon before age 25 years but then there is a steady rise to the time menopause, followed by a slower rise throughout life. The average age at diagnosis is 64 years.

Proliferative Breast Disease

Proliferative breast disease is associated with an increased risk as noted in the earlier discussion of this condition.

Carcinoma of the Contralateral Breast or Endometrium.

Increased risk is associated with carcinoma of contralateral breast or endometrium.

Radiation Exposure.

Women exposed to therapeutic radiation or after atom bomb exposure have a higher rate of breast cancer. Risk increases with younger is age and high radiation doses.

Geographic Influences

The incidence of breast cancer varies fourfold to sevenfold when Asian and other countries are compared with the United States and northern European countries having the highest rates. The specific factors have not been identified but probably include many of those listed in the following.

Age at First Child

Risk is increased in women older than 30 years at the time of their first child.

Obesity

There is decreased risk in ovese women younger than 40 owing to the association with anovulatory cycles and lower progestrone levels late in the cycle. There is increased risk postmenopausal obes women attributed to synthesis of estrogens in fat depots.

Genetic Factors

Genetic predisposition clearly exists, As noted germ line mutations in BRCA1 BRCA2 p53 a lucus on 10q in cowden syndrome and the ATM gene account for the majority of rare cases of autosomally inherited familial cancer. These genes probably act as tumor suppressor genes or in DNA repair and the features of BRCA1 and BRCA2 that are salient to breast cancer.

Hormonal Incluences.

Endogenous estrogen excess, or more accurately, hormonal imbalance clearly plays a significant role. Many of the risk factors mentioned long duration of reproductive life, nulliparity and late age at first child imply increased exposure to estrogen peaks during the menstrual cycle. Functioning ovarian tumors that elaborate estrogens are associated with breast cancer in postmenopausal women. Mildly increased breast cancer risk has been documented in postmenopausal women with high normal levels of circulating estrogens. There are also hints of how the estrogens may act. Normal breast epithelium possesses estrogen and progesterone receptors. These have been identified in some but not all breast cancers.