A Prospective Study of the Development of Breast Cancer in 16,692 Women With Benign Breast Disease

Abstract

The authors studied the relation between benign breast disease and subsequent breast cancer in 16,692 women with biopsy-diagnosed benign breast disease who had participated in the Breast Cancer Detection Demonstration Project throughout the United States. Women were classified into one of five benign breast disease categories: atypical hyperplasia, proliferative disease without atypia, nonproliferative disease, fibroadenoma, and other benign breast disease. A total of 485 incident cases of breast cancer were identified in the women from August 1973 to February 1986 after a median follow-up period of 8.3 years from the diagnosis of benign breast disease. Age-adjusted incidence rates were calculated for benign breast disease types stratified by family history and calcification status. Relative risk (RR) estimates of breast cancer for women in the five benign breast disease categories, compared with the screened women who did not develop recognizable breast disease (normal subjects), were computed using the proportional hazards model. Results indicated that risk was associated with the degree of epithelial atypia. Over all age groups, women with nonproliferative disease, proliferative disease without atypia, and atypical hyperplasia displayed progressively increasing risks of 1.5, 1.9, and 3.0, respectively, compared with normal subjects, with 95% confidence intervals (CI) exceeding unity. Particularly high risk was seen among women under age 46 years with atypical hyperplasia (RR = 5.7, 95% CI 3.0-10.6). Women with fibroadenoma as the only indication of their benign breast disease had a relative risk of 1.7, with a lower 95% confidence limit of 1.0. No increased risk was seen for women with other benign breast disease. Positive family history (RR = 1.8) and calcification (RR = 1.2) significantly increased a woman's risk proportionately over the risk associated with each benign breast disease subtype. The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: A nested case‐control study in Shanghai, China

“…In both incidences, the relative risks are probably underestimated because prior breast lumps that developed after the baseline questionnaire was administered were not included. These findings are consistent with the results from prospective studies [1][2][3][4][5][6][7][8] showing risk of breast cancer to be greater and more consistently observed in women with proliferative than non-proliferative benign breast conditions, and they are supportive of the hypothesis that breast carcinomas may arise from benign proliferative epithelium. Conversely, we observed about a 3-fold increased risk of fibrocystic breast conditions alone and about a 6-fold increased risk of breast cancer in women with a first-degree relative with breast cancer; and these associations were observed both in women with proliferative and non-proliferative benign breast conditions.…”

“…1 Although nonproliferative breast conditions do not seem to be associated with increased risk of breast cancer, proliferative fibrocystic breast conditions without and with atypia have been associated with 2-fold and 4-fold increased risks of breast cancer, respectively. [2][3][4][5][6][7][8] Most women who are diagnosed with proliferative fibrocystic breast conditions do not develop breast cancer, however, suggesting the presence of risk factors necessary for progression.…”

Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women

“…12 Benign breast disease, particularly atypical hyperplasia, is associated with increased breast cancer risk. 30,31 Given that prolactin is produced in normal and malignant breast tissue, 7,32 prolactin levels may differ in women with a history of benign breast disease, compared with those without such history. To our knowledge, we are the first to examine this association.…”

Management of breast fibroadenomas

“…The first issue was originally assessed in several retrospective studies, 14,[35][36][37][38][39][40][41] which demonstrated a 1.3 to 2.1 increased risk of breast cancer in women with fibroadenomas compared with the general population. The elevated risk was persistent, and did not decrease with time.…”