Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort.

ABSTRACT: Nonsteroidal 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 RELEVANCE: We 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.

Fibrocystic Breast Changes.

Fibrocystic changes in the breasts are the most common benign breast condition globally, with as many as 50% of women experiencing symptoms during their lifetime. This article explores the types of changes associated with fibrocystic breasts along with signs and symptoms, etiology and possible risk factors, diagnostic techniques, and treatments of fibrocystic breast changes, including lifestyle modifications, cyst drainage, and medications.

Positive association between SRA1 rs801460 variant and proliferative type of benign breast disease with atypia in Ukrainian females.

AIM: To investigate the association between SRA1 rs801460 and rs10463297 variants and proliferative type of benign breast disease with atypia development in Ukrainian females. MATERIALS AND METHODS: 83 individuals diagnosed with proliferative type of benign breast disease with atypia and 115 without atypia were enrolled in the study. The rs801460 and rs10463297 variants genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Hematoxylin and eosin, toluidine blue and van Gieson's picrofuchsin methods were used for sections staining. RESULTS: It was revealed that SRA1 rs801460-variant is associated with proliferative type of benign breast disease with atypia development both before and after adjustment for risk factors (age, body mass index, age of menarche, oral contraceptives intake and burdened history of breast cancer). The risk for mentioned disease in the individuals with rs801460 TT-genotype is 2.2 times higher (confidence interval 1.010-4.800; p = 0.047) than in individuals with the CC and CT genotypes. No link between SRA1 rs10463297 and proliferative type of benign breast disease with atypia occurrence in Ukrainian females was found. CONCLUSION: The present study specified that SRA1 rs801460, but not rs10463297, can be the strong genetic predictor for benign breast disease with atypia in Ukrainian females.

Polycystic Ovary Syndrome and Fibrocystic Breast Disease: An Updated Review.

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in women of reproductive age. There is no clear association between PCOS and benign breast disease (BBD). The latter is a frequent benign disorder, affecting women between 20 and 50 years of age. To date, the classification remains controversial, and the risk of developing breast cancer that is associated with these changes is different depending on the histopathological findings. The most frequent changes are breast cysts, which are noted in up to 50% of patients older than 30 years of age. This up-to-date review presents the relationship between PCOS and BBD. In conclusion, there is no clear association between benign breast disease and PCOS. Further studies on a large population with prospectively collected data using updated PCOS criteria are necessary.

Differences in breast cancer risk after benign breast disease by type of screening diagnosis.

INTRODUCTION: We aimed to assess differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens. MATERIALS AND METHODS: We conducted a retrospective cohort study with data from 629,087 women participating in a long-standing population-based breast cancer screening program in Spain. Each benign breast disease was classified as non-proliferative, proliferative without atypia, or proliferative with atypia, and whether it was diagnosed in a prevalent or incident screen. We used partly conditional Cox hazard regression to estimate the adjusted hazard ratios of the risk of breast cancer. RESULTS: Compared with women without benign breast disease, the risk of breast cancer was significantly higher (p-value = 0.005) in women with benign breast disease diagnosed in an incident screen (aHR, 2.67; 95%CI: 2.24-3.19) than in those with benign breast disease diagnosed in a prevalent screen (aHR, 1.87; 95%CI: 1.57-2.24). The highest risk was found in women with a proliferative benign breast disease with atypia (aHR, 4.35; 95%CI: 2.09-9.08, and 3.35; 95%CI: 1.51-7.40 for those diagnosed at incident and prevalent screens, respectively), while the lowest was found in women with non-proliferative benign breast disease (aHR, 2.39; 95%CI: 1.95-2.93, and 1.63; 95%CI: 1.32-2.02 for those diagnosed at incident and prevalent screens, respectively). CONCLUSION: Our study showed that the risk of breast cancer conferred by a benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyse the impact of the screening type on benign breast disease prognosis.

Macrophagic "Crown-like Structures" Are Associated with an Increased Risk of Breast Cancer in Benign Breast Disease.

In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). Although CLS-B have been associated with breast cancer, their role in benign breast disease (BBD) and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 years), including normal tissue donors of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 years). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with BBD: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86 = 18.6%, P = 0.01) and BBD cases (21/86 = 24%, P = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7% CLS-B positive, BMI 25-29: 13%, and BMI ≥ 30: 29% (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample: 10.5% (BBD cases) vs 4.7% (BBD controls), P = 0.007] conferred a breast cancer OR of 6.8 (95% CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area (cm2), histologic impression, and BMI. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9. ©2017 AACR.

NanoString-based breast cancer risk prediction for women with sclerosing adenosis.

PURPOSE: Sclerosing adenosis (SA), found in » of benign breast disease (BBD) biopsies, is a histological feature characterized by lobulocentric proliferation of acini and stromal fibrosis and confers a two-fold increase in breast cancer risk compared to women in the general population. We evaluated a NanoString-based gene expression assay to model breast cancer risk using RNA derived from formalin-fixed, paraffin-embedded (FFPE) biopsies with SA. METHODS: The study group consisted of 151 women diagnosed with SA between 1967 and 2001 within the Mayo BBD cohort, of which 37 subsequently developed cancer within 10 years (cases) and 114 did not (controls). RNA was isolated from benign breast biopsies, and NanoString-based methods were used to assess expression levels of 61 genes, including 35 identified by previous array-based profiling experiments and 26 from biological insight. Diagonal linear discriminant analysis of these data was used to predict cancer within 10 years. Predictive performance was assessed with receiver operating characteristic area under the curve (ROC-AUC) values estimated from 5-fold cross-validation. RESULTS: Gene expression prediction models achieved cross-validated ROC-AUC estimates ranging from 0.66 to 0.70. Performing univariate associations within each of the five folds consistently identified genes DLK2, EXOC6, KIT, RGS12, and SORBS2 as significant; a model with only these five genes showed cross-validated ROC-AUC of 0.75, which compared favorably to risk prediction using established clinical models (Gail/BCRAT: 0.57; BBD-BC: 0.67). CONCLUSIONS: Our results demonstrate that biomarkers of breast cancer risk can be detected in benign breast tissue years prior to cancer development in women with SA. These markers can be assessed using assay methods optimized for RNA derived from FFPE biopsy tissues which are commonly available.

Standardized measures of lobular involution and subsequent breast cancer risk among women with benign breast disease: a nested case-control study.

Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed whether three standardized measures of TDLU involution, with high intra/inter pathologist reproducibility in normal breast tissue, predict subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort. We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls. We assessed three metrics inversely related to TDLU involution: TDLU count/mm(2), median TDLU span (microns, which approximates acini content), and median category of acini counts/TDLU (0-10; 11-20; 21-30; 31-50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In multivariable models, women in the highest quartile compared to the lowest quartiles of TDLU counts and TDLU span measures were significantly associated with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1, OR = 2.44, 95 %CI 0.96-6.19, p-trend = 0.02; and TDLU spans, quartile4 versus quartile1, OR = 2.83, 95 %CI = 1.13-7.06, p-trend = 0.03. Significant associations with categorical measures of acini counts/TDLU were also observed: compared to women with median category of <10 acini/TDLU, women with >25 acini counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03-11.17, p-trend = 0.032. Women with TDLU spans and TDLU count measures above the median were at further increased risk, OR = 3.75 (95 %CI 1.40-10.00, p-trend = 0.008), compared with women below the median for both of these metrics. Similar results were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU count. Standardized quantitative measures of TDLU counts and acini counts approximated by TDLU span measures or visually assessed in categories are independently associated with breast cancer risk. Visual assessment of TDLU numbers and acini content, which are highly reproducible between pathologists, could help identify women at high risk for subsequent breast cancer among the million women diagnosed annually with BBD in the US.