Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas.

JAMA Oncol
Authors
Abstract

Importance: African Americans have the highest breast cancer mortality rate. Although racial difference in the distribution of intrinsic subtypes of breast cancer is known, it is unclear if there are other inherent genomic differences that contribute to the survival disparities.

Objectives: To investigate racial differences in breast cancer molecular features and survival and to estimate the heritability of breast cancer subtypes.

Design, Setting, and Participants: Among a convenience cohort of patients with invasive breast cancer, breast tumor and matched normal tissue sample data (as of September 18, 2015) were obtained from The Cancer Genome Atlas.

Main Outcomes and Measures: Breast cancer–free interval, tumor molecular features, and genetic variants.

Results: Participants were 930 patients with breast cancer, including 154 black patients of African ancestry (mean [SD] age at diagnosis, 55.66 [13.01] years; 98.1% [n = 151] female) and 776 white patients of European ancestry (mean [SD] age at diagnosis, 59.51 [13.11] years; 99.0% [n = 768] female). Compared with white patients, black patients had a worse breast cancer-free interval (hazard ratio, HR=1.67; 95% CI, 1.02-2.74; P = .043). They had a higher likelihood of basal-like (odds ratio, 3.80; 95% CI, 2.46-5.87; P 

Conclusions and Relevance: On the molecular level, after adjusting for intrinsic subtype frequency differences, this study found a modest number of genomic differences but a significant clinical survival outcome difference between blacks and whites in The Cancer Genome Atlas data set. Moreover, more than 40% of breast cancer subtype frequency differences could be explained by genetic variants. These data could form the basis for the development of molecular targeted therapies to improve clinical outcomes for the specific subtypes of breast cancers that disproportionately affect black women. Findings also indicate that personalized risk assessment and optimal treatment could reduce deaths from aggressive breast cancers for black women.

Year of Publication
2017
Journal
JAMA Oncol
Volume
3
Issue
12
Pages
1654-1662
Date Published
2017 12 01
ISSN
2374-2445
DOI
10.1001/jamaoncol.2017.0595
PubMed ID
28472234
PubMed Central ID
PMC5671371
Links
Grant list
U01 CA179715 / CA / NCI NIH HHS / United States
U54 CA156733 / CA / NCI NIH HHS / United States
U24 CA210978 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
P50 CA125183 / CA / NCI NIH HHS / United States
U01 CA161032 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U54 CA156735 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P50 CA058223 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
DP2 OD007149 / OD / NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States