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. 2023 Aug 1;6(8):e2331295.
doi: 10.1001/jamanetworkopen.2023.31295.

Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors

Hari S Iyer  1   2 , Nur Zeinomar  1   2 , Angela R Omilian  3 , Marley Perlstein  1 , Melissa B Davis  4 , Coral O Omene  2   5 , Karen Pawlish  6 , Kitaw Demissie  7 , Chi-Chen Hong  3 , Song Yao  3 , Christine B Ambrosone  3 , Elisa V Bandera  1   2 , Bo Qin  1   2
Affiliations

Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors

Hari S Iyer et al. JAMA Netw Open. .

Abstract

Importance: Racial disparities in breast cancer (BC) survival arise from multilevel causes, which may exert influence at different stages of BC progression. Clarifying the importance of genetic and social factors could help prioritize interventions.

Objective: To jointly examine associations between African genetic ancestry, social environment, and mortality from any cause and BC in Black BC survivors.

Design, setting, and participants: This population-based cohort study enrolled self-identified Black women aged 20 to 75 years with histologically confirmed BC from June 2005 to May 2019 and followed them up until death or censoring in September 2021. Participants lived in 10 New Jersey counties. Data were analyzed between December 2022 and April 2023.

Exposures: A neighborhood socioeconomic status (nSES) index composed of census tract measures (education, income, wealth, employment status, and occupation) was linked to residential addresses at diagnosis. Percentage African ancestry was estimated using the ADMIXTURE program.

Main outcomes and measures: Sequentially adjusted (age adjusted: age and interview year; fully adjusted: age adjusted with individual SES, lifestyle factors, and comorbidities) logistic regression models were fit to estimate associations with tumor subtypes (estrogen receptor-negative [ER-] vs estrogen receptor-positive [ER+]; triple-negative breast cancer [TNBC] vs luminal A), and Cox models were fit for associations with all-cause mortality (ACM) and breast cancer-specific mortality (BCSM). Models for BCSM were fit using Fine-Gray competing risks models, and robust standard errors were used to account for census tract-level clustering.

Results: Among 1575 participants, median (IQR) African ancestry was 85% (76%-90%), and median (IQR) age was 55 (46-63) years. A 10-percentage point increase in African ancestry was associated with higher odds of ER- vs ER+ (adjusted odds ratio [aOR], 1.08; 95% CI, 0.98-1.18) and TNBC vs luminal (aOR, 1.15; 95% CI, 1.02-1.31) tumors, but not with ACM or BCSM. A 1-IQR increase in nSES was associated with lower ACM (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.63-0.93), and the HR for BCSM was less than 1 but not statistically significant (aHR, 0.81; 95% CI, 0.62-1.04) in age-adjusted models, but associations attenuated following further adjustment for potential mediators (individual SES, lifestyles, comorbidities).

Conclusions and relevance: In this cohort study of Black female BC survivors, higher African ancestry was associated with aggressive tumor subtypes. Compared with genetic ancestry, mediating pathways related to social environments may be more important for survival in these patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zeinomar reported receiving grants from National Cancer Institute during the conduct of the study. Dr Davis reported receiving grants from Breast Cancer Research Foundation during the conduct of the study as well as grants from Genentech and the National Cancer Institute and personal fees from Gilead Life Sciences outside the submitted work. Dr Demissie reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Bandera reported receiving personal fees from Pfizer outside of the submitted work. Dr Qin reported receiving grants from NIH during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Survival Curves for All-Cause Mortality by Quartiles (Q) of African Ancestry and Neighborhood Socioeconomic Status (nSES) in 1575 Black Women with Breast Cancer, New Jersey, 2006 to 2020
P value for log-rank test.
See this image and copyright information in PMC

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