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Zirpoli, Gary R.

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Zirpoli

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Gary R.

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Zirpoli, Gary R.

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2017 - 20182

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Author's Publications: search.filters.isAuthorOfPublication.293da478-573c-4762-9950-da9f47a1be5c

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    Frequency of breast cancer subtypes among African American women in the AMBER consortium
    (BioMed Central, 2018) Allott, Emma H.; Geradts, Joseph; Cohen, Stephanie M.; Khoury, Thaer; Zirpoli, Gary R.; Bshara, Wiam; Davis, Warren; Omilian, Angela; Nair, Priya; Ondracek, Rochelle P.; Cheng, Ting-Yuan David; Miller, C. Ryan; Hwang, Helena; Thorne, Leigh B.; O’Connor, Siobhan; Bethea, Traci N.; Bell, Mary E.; Hu, Zhiyuan; Li, Yan; Kirk, Erin L.; Sun, Xuezheng; Ruiz-Narvaez, Edward A.; Perou, Charles M.; Palmer, Julie R.; Olshan, Andrew F.; Ambrosone, Christine B.; Troester, Melissa A.
    Background: Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Methods: Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression. Results: Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%). Conclusions: Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women. Electronic supplementary material The online version of this article (10.1186/s13058-018-0939-5) contains supplementary material, which is available to authorized users.
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    Genetic variations, reproductive aging, and breast cancer risk in African American and European American women: The Women's Circle of Health Study
    (Public Library of Science, 2017) Coignet, Marie V.; Zirpoli, Gary R.; Roberts, Michelle R.; Khoury, Thaer; Bandera, Elisa V.; Zhu, Qianqian; Yao, Song
    Reproductive aging phenotypes, including age at menarche (AM) and age at natural menopause (ANM), are well-established risk factors for breast cancer. In recent years, many genetic variants have been identified in association with AM and ANM in genome-wide association studies among European populations. Using data from the Women’s Circle of Health Study (WCHS) of 1,307 European-American (EA) and 1,365 African-American (AA) breast cancer cases and controls, we aimed to replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast cancer risk was also examined in relation to a polygenic risk score (PRS) for each of the reproductive aging phenotypes. We replicated a number of variants in EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM; whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was directionally consistent and nominally significant. In analysis of TRLS and NRLS, several SNPs were significant, including rs466639 in RXRG that was associated with both phenotypes in both AA and EA groups. None of the PRS was associated with breast cancer risk. Given the paucity of data available among AA populations, our study contributes to the literature of genetics of reproductive aging in AA women and highlights the importance of cross population replication of GWAS variants.