[ PRINT ] [ Printing FAQ ] About OncoLink Editorial Board Sponsors Help See Today's OncoTip Usage Statistics Virtual Classroom Abramson Family Cancer Research Institute "Confronting Cancer Through Art" is an exhibition by people whose lives have been touched by cancer. This week we are featuring artwork by: Jacqueline Kniewasser Pontypool, Ontario Visit the Children's Art Gallery This week's artwork was donated by a pediatric cancer patient who received treatment for cancer at The Children's Hospital of Philadelphia.

Risk Factors and Breast Cancer Authors: OncoLink Team Affiliations: University of Pennsylvania Cancer Center Last Revision Date: Sunday, 14-Feb-1999 13:54:26 EST Copyright © 1994-1999, The Trustees of the University of Pennsylvania Risk Factors and Breast Cancer The risk of an American woman developing breast cancer during her lifetime is approximately 11%, with approximately 3-4% dying of the disease. Several factors appear to increase the risk of developing breast cancer, including family history, reproductive history, diet, hormone usage, and radiation exposure. Despite the recognition of these risk factors, approximately 70% of the women who develop breast carcinomas do not have any of these identifable risk factors. Many studies link breast cancer incidence with the age of menarche and the establishment of of regular ovulatory cycles. On study infers a 20% decrease in breast cancer risks for every year that menarche is delayed. The late onset of menarche is associated with a delay in the establishment of regular ovulatory cycles, which may have some sort of protective effect. This is a hotly contested theory. A woman's physical activity level, even if moderate, can have an impact on the likelihood of ovulatory cycles and may later breast cancer risk. The age-specific incidence of breast cancer rises at a steep rate with age up to the time of menopause and then slows to a rate one sixth of that seen in the premenopausal period. It has been suggested that this age-specific incidence curve is shaped largely by the effects of ovarian activity. Age at menopause is another factor of breast cancer risk, with a slightly decreased risk of breast cancer for a woman with natural menopause before age 4 (0.73) compared with a woman with natural menopause between the ages of 45-54. Oophorectomy before the age of 50 decreases breast cancer risk. This data indicates the total duration of menstrual life is an important factor in breast cancer risk, although the mechanisms to explain this observation are presently unclear. Parity (having children) and the age of the woman at the birth of her first offspring are other enodgenous hormonal factors that influence breast cancer. Women who have never had children (nulliparous) are at greater risk for the development of breast cancer than women who have had children (parous), with a risk factor of approximately 1.4. The effect of term pregnancy on breast cancer risk varies with the age of the mother's first birth, with women whose first pregnancy occurs after age 30 having a 2-5 fold increase in breast cancer risk compared with women having a first term pregnancy before age 18 or 19. Abortion, whether spontaneous or induced, before full-term pregnancy, appaers to have no protective effect. In some studies, premature termination of pregnancy appears to increase breast cancer risk. This apparent contradiction might be explained by the sustained level of hormones in a term pregnancy. Breast tissue may undergo differentiation as a result of hormonal changes of pregnancy. These differentiated cells are less likely to undergo malignant transformation. In incomplete pregnancy, the breast is exposed only to the high estrogen levels of early pregnancy and thus may be responsible for the increase risk seen in these women. The associations between the use of oral contraceptives and postmenopausal estrogen replacement and breast cancer have been studied. Many studies attempting to link oral contraceptives with increased breast cancer have been inconclusive. While there are isolated incidences of heightened breast cancer where oral contraceptives have been implicated, the Centers for Disease Control's Cancer and Steroid Hormone study failed to find any increase in risk related to duration of oral contraceptive use or in users with a family history of breast cancer or a personal history of benign breast disease. Currently, there is no compelling evidence to avoid the use of oral contraceptives for any subgroup of patients. These studies are complicated by the inclusion of women treated with higher doses of estrogen in their contraceptive pills. Since 1960, the average estrogen content of estrogen pills has dropped from 150 to 35mg. The use of postmenopausal estrogen replacement therapy may be associated with a small increase in breast cancer risk in the range of 1.5 - 2.0 for moderate dose conjugated estrogen therapy lasting for 10 to 20 years. While the use of short term estrogen replacement therapy appears to be safe, there is little information available pertaining to the long term, low dose therapy. In evaluating the potential risks of breast cancer from estrogen therapy, the proven benefits in reducing osteoporosis and susequent fracture and lowering the risk of coronary artery disease must be taken into account. A possible relationship between breast cancer and diet has been suggested due to the variation of breast cancer in societies with different national diets. That these differences are not solely due to genetics is suggested by a study of migrants. Japanese women immigrating to the United States and first-generation American born Japanese women were found to have an incidence almost identical to whites in the same area and considerably higher than that of women in Japan. Although this observation implicates environmental factors as playing an important role in breast cancer incidence, it does not implicate breast cancer as the sole cause of the observed differences. A comparison of vegetarian versus meat-eating women produced inconclusive results. Breast cancer mortality among Seven Day Adventists, a religious group that eats a diet low in animal fats, is not significantly different from women who consume an average American amount of dietary fats. In the largest prospective study dietary fat, 89,538 nurses between the ages of 34 and 59 were studied. No relation between breast cancer risk and total fat, saturated fat, linoleic acid, or cholesterol was found. The differences in fat intake between the highest and lowest fat consumers was only 25%, suggesting dietary fat reduction in the context of the usual American diet is unlikely to reduce breast cancer. A positive, but modest association between alcohol use and breast cancer risk is seen in most studies. There appears to be a relative risk of breast cancer risk of 1.4 for women with an alcohol intake of two drinks per day. While a large study sponsored by the American Cancer Society found no increase in risk for occasional users of alchohol, the risk was elevated in all other categories of alchohol use. Several studies have found alcohol to have its greatest effect on breast cancer risk in women under the age of 30. Women with a family history of breast cancer in a first- or second-degree relative are at a higher risk for developing breast cancer. The risk of developing breast cancer is 1.5 to 3.0 times higher if a mother or sister has the disease, and the risk may be greater if a sibling is affected (versus the mother). The higher incidence doesn't seem to matter whether the relative's occurrence was premenopasual or postmenopausal. Bilateral premenopausal breast cancer in a relative has been associated with the highest risk of breast cancer development. For most people with a family history of breast cancer, the lifetime probability of developing breast cancer is rarely greater than 30%, and the magnitude of risk conferred by a positive family history is similar to that seen with many other risk factors. Only 5% of carefully studied breast cancer patients are thought to have a pedigree consistent with hereditary brast cancer. Breast cancer is observed as part of cancer family syndromes in association with other tumors, as listed below: Breast Cancer in Hereditary Syndromes Syndrome Sites of Other Tumors Li-Fraumeni Syndrome Sarcomas (e.g. soft tissue, bone), brain tumors brain tumors, leukemia, adrenocortical carcinoma Cowden's Disease Facial trichilemmomas, papillomatosis of lips and oral mucosa, acral keratoses, gastrointestinal polyps, uterine leiomyomata Muir Syndrome Basal cell carcinoma, benign and malignant gastrointestinal tumors Epidemiologic studies of women exposed to ionizing radiation due to nuclear war or diagnostic or therapeutic procedures have an increased risk for the development of breast carcinomas. Multiple chest fluroscopies, breast irradiation for mastitis, and thymic irradiation increase breast cancer risk. There is a long latent period for radiation-induced breast cancer, and the risk of developing the disease is related to the age of the radiation exposure. Radiation after the age of 40 results in a minimal increase in risk, and radiation in adolescence is associated with the greatest risk of breast cancer development. Girls irradiated during infancy for thymic enlargement had a linear dose-response risk for subsequent breast cancer development. Correlating breast cancer risk with benign breast disease cannot be made without specific knowledge of the histological features of the biopsy. Fibrocystic disease includes a heterogeneous group of pathological changes associated with various degrees of breast cancer risk. Benign breast conditions are classified as nonproliferative or proliferative and on the basis or a review of more than 10,000 breast biopsies, relative risks of breast cancer were determined. Women with proliferative disease were found to have a relative risk of 1.9, and the subcategory of women with atypical hyperplasia were found to have a relative risk of 4.4. Nonproliferative breast disease was associated with no excess of breast cancer. Sixty-nine percent of the reviewed biopsies were found to hasve nonproliferative breast disease, and of the biopsies demonstrating nonproliferative changes, only 3.6% were atypical. These were classified as follows: Classification of Benign Breast Disease Nonproliferative adenosis cysts, macro or micro duct ectasia fibroadenoma fibrosis mastitis metaplasia, apocrine or squamous mild hyperplasia Proliferative moderate or florid hyperplasia papilloma with fibrovascular core atypical hyperplasia, ductal or lobular There are no interventions proven to decrease risk. The data on the use of exogenous hormones are controversial enough that a firm recommendation to avoid their use cannot be made. Similarly, the link between dietary fat and breast cancer is weak, and there is little evidence to suggest that altering the diet or alcohol consumption in the adult life changes breast cancer risk. Patient education, with instructions in breast self-examination, regular physical examinations every four to six months, and mammography in accordance with standard guidelines are appropriate surveillance techniques.

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