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Risk factors for breast cancer from benign breast disease in a diverse population.

ABSTRACT: The majority of studies have reported risks of breast cancer (BC) from benign breast disease (BBD) in essentially homogenous Caucasian populations. Information on breast cancer risk factors in larger, multi-ethnic populations should facilitate the development of appropriate and targeted risk reduction strategies.Cases and controls were drawn from a parent BBD cohort of 4,970 women, 1,341 African-Americans (AA) and 3,629 non-AA who were diagnosed with BBD after examination of an excisional breast biopsy. Risk factors (34 variables) included demographics, lesion types, and epidemiological variables.The final multivariable model retained significance (P < 0.05) for lesion risk-level, fibroadenoma, and the interaction of age-by-race. Women with proliferative lesions (no atypia, risk level 2) were 1.7 times more likely to develop BC when compared with women with non-proliferative lesions (OR = 1.7, 95% CI 1.13, 2.42, P = 0.009). Women with atypia (risk level 3) were 3.75 times more likely to develop BC compared to women with non-proliferative lesions (OR = 3.75, 95% CI 1.99, 7.06, P < 0.001). The odds of breast cancer was approximately 35% lower among women with fibroadenoma as compared to women without fibroadenoma (OR = 0.65, 95% CI 0.46, 0.94, P = 0.020). AA women with BBD who were 50 years or older were 2.28 times more likely to develop breast cancer as compared to non-AA women who were less than 50 years old (OR = 2.28, 95% CI 1.34, 3.88, P = 0.002).Women with fibroadenoma (nonproliferative or proliferative) were less likely to progress to BC. Older AA women are at greater risk for progression to breast cancer from BBD.

SUBMITTER: Worsham MJ

PROVIDER: S-EPMC3715322 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Risk factors for breast cancer from benign breast disease in a diverse population.

Worsham Maria J MJ Raju Usha U Lu Mei M Kapke Alissa A Botttrell Alyssa A Cheng Jingfang J Shah Varsha V Savera Adnan A Wolman Sandra R SR

Breast cancer research and treatment 20081004 1

<h4>Background</h4>The majority of studies have reported risks of breast cancer (BC) from benign breast disease (BBD) in essentially homogenous Caucasian populations. Information on breast cancer risk factors in larger, multi-ethnic populations should facilitate the development of appropriate and targeted risk reduction strategies.<h4>Design</h4>Cases and controls were drawn from a parent BBD cohort of 4,970 women, 1,341 African-Americans (AA) and 3,629 non-AA who were diagnosed with BBD after e ...[more]

PMID: 18836828

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Project description:BackgroundBenign breast disease (BBD) is a risk factor for breast cancer (BC); however, little is known about the genetic alterations present at the time of BBD diagnosis and how these relate to risk of incident BC.MethodsA subset of a long-term BBD cohort was selected to examine DNA variation across three BBD groups (42 future estrogen receptor-positive (ER+) BC, 36 future estrogen receptor-negative (ER-) BC, and 42 controls cancer-free for at least 16 years post-BBD). DNA extracted from archival formalin fixed, paraffin-embedded (FFPE) tissue blocks was analyzed for presence of DNA alterations using a targeted panel of 93 BC-associated genes. To address artifacts frequently observed in FFPE tissues (e.g., C>T changes), we applied three filtering strategies based on alternative allele frequencies and nucleotide substitution context. Gene-level associations were performed using two types of burden tests and adjusted for clinical and technical covariates.ResultsAfter filtering, the variant frequency of SNPs in our sample was highly consistent with population allele frequencies reported in 1 KG/ExAC (0.986, p < 1e-16). The top ten genes found to be nominally associated with later cancer status by four of 12 association methods(p < 0.05) were MED12, MSH2, BRIP1, PMS1, GATA3, MUC16, FAM175A, EXT2, MLH1 and TGFB1, although these were not statistically significant in permutation testing. However, all 10 gene-level associations had OR < 1 with lower mutation burden in controls compared to cases, which was marginally statistically significant in permutation testing (p = 0.04). Comparing between the three case groups, BBD ER+ cases were closer to controls in mutation profile, while BBD ER- cases were distinct. Notably, the variant burden was significantly higher in controls than in either ER+ or ER- cases. CD45 expression was associated with mutational burden (p < 0.001).ConclusionsSomatic mutations were more frequent in benign breast tissue from women who did not develop cancer, opening questions of clonal diversity or immune-mediated restraint on future cancer development. CD45 expression was positively associated with mutational burden, most strongly in controls. Further studies in both normal and premalignant tissues are needed to better understand the role of somatic gene mutations and their contribution to future cancer development.

Project description:AbstractNonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78-0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74-0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59-1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92-1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted.Prevention relevanceWe examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.

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Risk factors for breast cancer from benign breast disease in a diverse population.

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Risk factors for breast cancer from benign breast disease in a diverse population.

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