Daaboul, Mhd Fayez

Abstract Introduction: Atypical hyperplasia (also known as proliferative disease with atypia), while categorized as a benign finding, has been consistently associated with an increased risk of subsequent breast cancer that persists for decades after initial diagnosis. There are various other lesions that are classified as benign breast disease (BBD) that are routinely identified by pathologists that may also increase risk and be of use to inform breast cancer risk models. We sought to identify which BBD lesions were associated with increased risk of breast cancer in an African American (AA) cohort. Methods: Benign breast biopsies from 3,895 AA women diagnosed with BBD between 1997 and 2010 in metropolitan Detroit were reviewed for 12 benign features including columnar alterations, ductal ectasia, ductal hyperplasia, fibrosis, apocrine metaplasia, lobular hyperplasia, calcifications, cysts, intraductal papilloma, radial scar, sclerosing adenosis, and fibroadenomas. Women were followed for subsequent breast cancer using the Metropolitan Detroit Cancer Surveillance System, part of the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Associations between BBD features and subsequent breast cancer were examined using chi-square tests. Features that had a significant chi-square test result were also combined into scores describing the overall number of BBD features identified, termed busy breast score. Multivariable log-binomial regression with backward selection based on BIC criteria was performed to assess risk ratio and 95% confidence intervals of breast cancer on 12 candidate features. Multivariable log-binomial regression was performed for busy breast score as well. All regression models were adjusted for age at biopsy and overall impression for presence of proliferative disease with or without atypia using non-proliferative disease as the reference. Models were checked for multicollinearity using a variable inflation factor (VIF). Results: Of the 3,895 AA women in the BBD cohort, 210 developed a subsequent breast cancer. The median age at biopsy among those without a subsequent cancer (controls) was 47 years of age, while cases were 53 years of age (p-value<0.001). In univariate analyses, ductal hyperplasia (p-value=0.001), lobular hyperplasia (p-value<0.001), calcifications (p-value<0.004), cysts (p-value=0.003), intra-ductal papilloma (p-value=0.005), sclerosing adenosis (p-value=0.002), columnar alterations (p-value<0.001) and radial scar (p-value=0.001) were associated with subsequent breast cancer. Fibroadenomas were inversely associated with subsequent breast cancer (p-value<0.001). In multivariable model after backwards selection, presence of columnar alterations was associated with increased risk of breast cancer, (RR=1.57, 95% CI: 1.16, 2.13). Combining the 9 BBD features associated with subsequent breast cancer in univariate analysis, those with a busy breast score of 5+ was associated with 2.5 times increased risk compared to those with none of these features (RR=2.52, 95% CI: 1.41, 4.49). As a continuous variable for busy breast score, each additional feature conferred a 20% increase in risk of breast cancer (RR=1.20, 95% CI: 1.10, 1.31). Conclusions: Columnar alterations confer increased risk of breast cancer beyond the risks associated with atypical hyperplasia, as does the presence of multiple types of BBD lesions in a single biopsy. These estimates may help improve the current risk assessment models for African American women and highlight the need for additional research regarding the utility of closer surveillance and potentially chemoprevention for reduction of breast cancer in these women. Citation Format: Michele L. Cote, Wei Chen, Julie J. Ruterbusch, Eman Abdulfatah, Visakha Pardeshi, Asra N. Shaik, Marcel T. Ghanim, MHD Fayez Daaboul, Daniel W. Visscher, Sudeshna Bandyopadhyay, Rouba Ali-Fehmi. Benign breast disease and subsequent breast cancer risk: The Detroit cohort. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A25.

Abstract Introduction: The majority of the 1.6 million breast biopsies performed annually in the United States are benign; however, several breast cancer risk models consider a benign biopsy a factor that increases risk of subsequent breast cancer. Fibroadenomas (FA), benign tumors of epithelial and stromal tissue, occur frequently in premenopausal women and more frequently in African American (AA) women than European American (EA) women. A small increased risk of subsequent breast cancer due to FA has been reported in some studies of EA women. We sought to investigate whether the risk of this lesion differs for AA women. Methods: Benign breast biopsies from 3895 AA women diagnosed between 1997 and 2010 in metropolitan Detroit were reviewed for 12 benign features including FA, ductal ectasia, fibrosis, apocrine metaplasia, ductal hyperplasia, lobular hyperplasia, calcifications, cysts, intraductal papilloma, radial scar, sclerosing adenosis, and columnar alterations. These features were also used to categorize FA into simple and complex FA, where complex FA occurs when FA is accompanied by at least one of the following features: cysts, calcifications, apocrine metaplasia or intraductal papilloma. Women were followed for subsequent breast cancer using the Detroit Surveillance, Epidemiology, and End Results (SEER) cancer registry. Associations between FA and other benign lesions were examined using chi-square tests. Risk of breast cancer was estimated by relative risk ratios and 95% confidence intervals calculated using logistic regression. All models were adjusted for age at biopsy and additionally adjusted for presence of proliferative disease with or without atypia. Results: Of the 3895 AA women, 46.5% presented with FA on biopsy. FA occurred more frequently in biopsies of younger women (p-value < 0.001) and were less likely to include the other benign lesions assessed (all p-value < 0.001). Of the 210 identified breast cancers that developed in this cohort, 72 cancers developed in women with FA on biopsy. FA were associated with a reduction in risk of breast cancer after adjusting for age at biopsy (RR=0.64, 95% CI: 0.48, 0.86) compared to women without FA on biopsy. Reduction in risk was somewhat attenuated when analysis was adjusted for proliferative disease with or without atypia (RR = 0.67, 95%CI: 0.48, 0.936). Similar associations were seen with simple FA (RR =0.61, 95% CI: 0.35, 1.01) and complex FA (RR =0.70, 95% 0.35, 1.01) after adjustment for age at biopsy and proliferative disease with or without atypia. Conclusions: FA are negatively associated with other benign breast disease features. Risk of breast cancer may be reduced in women with FA compared to women with other types of benign lesions. These findings have important implications for modeling breast cancer risk particularly among AA women for whom FAs are common. Citation Format: Asra N. Shaik, Julie J. Ruterbusch, Eman Abdulfatah, Marcel T. Ghanim, MHD Fayez Daaboul, Visakha Pardeshi, Rouba Ali-Fehmi, Daniel W. Visscher, Sudeshna Bandyopadhyay, Michele L. Cote. Fibroadenomas on benign breast biopsy and subsequent breast cancer risk in an African American cohort. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A16.