Benign breast disease and the risk of breast cancer.
ABSTRACT Benign breast disease is an important risk factor for breast cancer. We studied a large group of women with benign breast disease to obtain reliable estimates of this risk.
We identified all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991. Breast-cancer events were obtained from medical records and questionnaires. To estimate relative risks, we compared the number of observed breast cancers with the number expected on the basis of the rates of breast cancer in the Iowa Surveillance, Epidemiology, and End Results registry.
We followed 9087 women for a median of 15 years. The histologic findings were nonproliferative lesions in 67 percent of women, proliferative lesions without atypia in 30 percent, and atypical hyperplasia in 4 percent. To date, 707 breast cancers have developed. The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia.
Risk factors for breast cancer after the diagnosis of benign breast disease include the histologic classification of a benign breast lesion and a family history of breast cancer.
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ABSTRACT: Benign breast disease (BBD) is a broad category of diagnoses reported to convey a variable degree of increased risk of developing breast cancer. A meta-analysis of the existing literature was performed to quantify the risk estimate associated with BBD. Pubmed, Google Scholar, and EMBASE databases were searched in January 2011. English retrospective and prospective observational studies published from 1972 to 2010 evaluating BBD and the risk of breast cancer were included with data acquisition reported from 1930 to 2007. Eligibility was performed independently following a standardized protocol for full-text publication review by a single reviewer and reviewed by a second author. Of the 3,409 articles retrieved from the literature search, 32 studies met the selection criteria. Reported risk estimates, including relative risk, odds ratio, standardized incidence ratios, rate ratio, hazards ratio, and incidence rate ratio, were the primary outcomes extracted. The most commonly reported pathologies were decided prior to extraction and organized into the following categories for analysis of the extracted risk estimate: non-proliferative disease (NPD), proliferative disease without atypia, benign breast disease not otherwise specified (BBD), and atypical hyperplasia not otherwise specified (AHNOS). The mean age at benign breast biopsy was 46.1 years and the mean age of developing breast cancer was 55.9 years. The mean follow-up length was 12.8 years (range 3.3-20.6). The summary risk estimate of developing breast cancer for NPD was 1.17 (N = 8; 95 % CI 0.94-1.47). Proliferative disease without atypia was associated with significantly increased risk of future breast cancer, summary relative risk 1.76 (N = 15; 95 % CI 1.58-1.95). The summary risk estimate for AHNOS was 3.93 (N = 13; 95 % CI 3.24-4.76). This meta-analysis demonstrates that proliferative benign breast disease with or without atypia is associated with a significant increase in risk of developing breast cancer. These data support management strategies for women with benign breast disease such as additional screening methods or chemoprevention.Breast Cancer Research and Treatment 01/2015; 149(3). DOI:10.1007/s10549-014-3254-6 · 4.20 Impact Factor
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ABSTRACT: Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times relative to that in the general population. Here, we sought to evaluate whether the proliferation marker Ki-67 stratifies risk among women with SA. A nested case-control sample of patients with SA was obtained from the Mayo Clinic Benign Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n = 133) or did not (controls, n = 239) develop BC. Ki-67 was scored by intensity and number of positively stained cells per one high-power field (magnification, ×40) (40× HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case-control status were assessed using conditional logistic regression. Higher Ki-67 expression was significantly associated with case-control status in both SA (P = 0.03) and normal background TDLU (P = 0.006). For the SA lesion, >2 average positively stained cells/40× HPF showed an adjusted odds ratio (OR) of 1.9 (95 % CI, 1.1-3.4) compared to samples with an average of ≤2 positively stained cells. For background TDLU, lobules with >2 but ≤6 average positively stained cells showed an adjusted OR of 1.3-1.5, whereas those with an average of >6 positively stained cells had an OR of 2.4 (95 % CI, 1.1-5.3) compared to those with an average of <2 positively stained cells. Among women with SA, increased Ki-67 expression in either the SA lesion or the normal background TDLU carried an approximately twofold increased odds of subsequent BC as compared to lower Ki-67 expression.Breast Cancer Research and Treatment 04/2015; 151(1). DOI:10.1007/s10549-015-3370-y · 4.20 Impact Factor
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ABSTRACT: Breast cancer is occasionally complicated by sclerosing adenosis (SA). Although both lesions usually originate in the terminal duct lobular unit, their pathogenetic relationship has not yet been elucidated. The present study analyzed 63 breast cancer patients with SA (involving a total of 75 breasts) to clarify if coexisting SA increased the frequency of multicentric breast cancer or not. Using the topographical classification proposed in our previous study, breast cancers with SA were classified into the following three types: type A (n = 22), cancer area was completely surrounded by the SA; type B (n = 26), cancer area partially overlapped the SA; and type C (n = 27), cancer area was located separate from the SA. Breast cancers with SA had a significant (P < 0.001) increase in frequency of harboring bilateral and multicentric cancers [17 of 63 (27 %) and 15 of 63 (24 %), respectively] when compared to breast cancer patients without SA, regardless of topographical type. Breast cancers with SA were less invasive (P < 0.001), of lower histological grade (P = 0.034), and had similar frequency of estrogen receptor-positive (P = 0.21) and HER2-positive (P = 0.74) tumors. In conclusion, contralateral and ipsilateral multicentric breast cancers occurred at a higher frequency in those with SA. Our data suggest that SA is, in addition to lobular neoplasia, a predictor of multicentric breast cancers.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2015; DOI:10.1007/s00428-015-1769-9 · 2.56 Impact Factor