Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 1;6(3):e233329.
doi: 10.1001/jamanetworkopen.2023.3329.

Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer

Fangyuan Zhao  1 , Minoru Miyashita  2   3 , Masaya Hattori  4 , Toshio Yoshimatsu  3 , Frederick Howard  3 , Kristiyana Kaneva  5 , Ryan Jones  5 , Joshua S K Bell  5 , Gini F Fleming  3 , Nora Jaskowiak  6 , Rita Nanda  3 , Yonglan Zheng  3 , Dezheng Huo  1   3 , Olufunmilayo I Olopade  3
Affiliations

Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer

Fangyuan Zhao et al. JAMA Netw Open. .

Abstract

Importance: Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT).

Objective: To investigate whether racial disparities exist in achieving pCR and what factors contribute to them.

Design, setting, and participants: Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine. Patients diagnosed between 2002 and 2020 (median follow-up: 5.4 years) were included; next-generation sequencing data on tumor-normal tissue pairs were available from 186 ChiMEC patients, including both primary and residual tumor samples. Statistical analysis was performed from September 2021 to September 2022.

Exposures: Demographic, biological, and treatment factors that could contribute to disparities in achieving pCR.

Main outcomes and measures: pCR was defined as the absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ.

Results: The study included 690 patients with breast cancer, with a mean (SD) age of 50.1 (12.8) years. Among the 355 White patients, 130 (36.6%) achieved pCR compared to 77 of the 269 Black patients (28.6%; P = .04). Not achieving pCR was associated with significantly worse overall survival (adjusted hazard ratio, 6.10; 95% CI, 2.80-13.32). Black patients had significantly lower odds of achieving pCR compared with White patients in the hormone receptor-negative/ERBB2+ subtype (adjusted odds ratio, 0.30; 95% CI, 0.11-0.81). Compared with White patients with ERBB2+ disease, Black patients were more likely to have MAPK pathway alterations (30.0% [6 of 20] vs 4.6% [1 of 22]; P = .04), a potential mechanism of anti-ERBB2 therapy resistance. Tumor mutational burden and somatic alterations in several genes (eg, FGF4, FGF3, CCND1, MCL1, FAT1, ERCC3, PTEN) were significantly different between the primary and residual tumors.

Conclusions and relevance: In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Fleming reported being a principal investigator for industry-sponsored trials for Roche, Syros, GSK, Sermonix, Compugen, Celldex, Abbvie, Corcept, AstraZeneca, Molecular Templates, CytomX, Astellas, and K-Group Beta; receiving personal fees from GSK Advisory Board; and serving on the advisory board for Tersera (uncompensated) outside the submitted work. Dr Nanda reported receiving personal fees from AstraZeneca, BeyondSpring, Cardinal Health, Fujifilm, GE, Immunomedics/Gilead, Infinity, iTeos, MacroGenics, Merck, OBI, Oncosec, Sanofi, and Seattle Genetics (advisory board), and grants from Arvinas, AstraZeneca, Celgene, Corcept Therapeutics, Genentech/Roche, Immunomedics/Gilead, Merck, OBI Pharma, Odonate Therapeutics, OncoSec, Pfizer, Relay, Seattle Genetics, Sun Pharma, and Taiho (research funding) outside the submitted work. Dr Olopade reported receiving grants from Tempus (scientific advisory board) during the conduct of the study; being cofounder of CancerIQ, serving as a board of directors member for 54gene, and receiving grants from Color Genomics (research support) and grants from Roche (clinical trial support for IIT) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overall Survival (OS) and Recurrence-Free Survival (RFS) Graphs Between Black and White Patients Stratified by Pathological Complete Response (pCR) Status
A, OS (defined as the time from the date of diagnosis to the date of death from any cause or date of last follow-up) graphs between Black and White patients stratified by pCR status. B, RFS (defined as the time from the date of diagnosis to the first appearance of one of the following: invasive recurrence of breast cancer, death from any cause or date of last follow-up) graphs between Black and White patients stratified by pCR status.
Figure 2.
Figure 2.. Mutational Landscape of Primary Tumor Samples From 114 Black and White Patients Stratified by Breast Cancer Subtypes
The Oncoprint demonstrated the genes that had point mutations, copy number variations, and/or chromosomal variation observed for at least 10% of the samples. Genes were ordered by decreasing frequency. Not all 153 primary tumor samples were plotted. Samples were not plotted if no alterations were observed for the listed genes, the subtype data were missing and/or they were collected from patients of other racial or ethnic groups. See eFigure 3 in Supplement 1 for a more comprehensive Oncoprint. ERBB2− indicates human epidermal growth factor receptor 2–negative; ERBB2+, human epidermal growth factor receptor 2–positive; HR−, hormone receptor–negative; HR+, hormone receptor–positive; TNBC, triple-negative breast cancer. aGenes that were previously reported as breast cancer driver genes.
Figure 3.
Figure 3.. Mutational Landscape of Residual Tumor Samples From 41 Black and White Patients Stratified by Breast Cancer Subtypes
The Oncoprint demonstrated the genes that had point mutations, copy number variations, and/or chromosomal variation observed for at least 7% of the samples. Genes were ordered by decreasing frequency. Not all 46 residual tumor samples were plotted. Samples were not plotted if no alterations were observed for the listed genes, the subtype data were missing and/or they were collected from patients of other racial/ethnic groups. See eFigure 4 in Supplement 1 for a more comprehensive Oncoprint. ERBB2− indicates human epidermal growth factor receptor 2–negative; ERBB2+, human epidermal growth factor receptor 2–positive; HR−, hormone receptor–negative; HR+, hormone receptor–positive; TNBC, triple-negative breast cancer. aGenes that were previously reported as breast cancer driver genes.
See this image and copyright information in PMC

References

    1. Lima SM, Kehm RD, Terry MB. Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinicalMedicine. 2021;38:100985. doi: 10.1016/j.eclinm.2021.100985 - DOI - PMC - PubMed
    1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi: 10.3322/caac.21660 - DOI - PubMed
    1. Ansari-Pour N, Zheng Y, Yoshimatsu TF, et al. Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes. Nat Commun. 2021;12(1):6946. doi: 10.1038/s41467-021-27079-w - DOI - PMC - PubMed
    1. Huo D, Hu H, Rhie SK, et al. Comparison of breast cancer molecular features and survival by African and European ancestry in The Cancer Genome Atlas. JAMA Oncol. 2017;3(12):1654-1662. doi: 10.1001/jamaoncol.2017.0595 - DOI - PMC - PubMed
    1. Pitt JJ, Riester M, Zheng Y, et al. Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nat Commun. 2018;9(1):4181. doi: 10.1038/s41467-018-06616-0 - DOI - PMC - PubMed

Publication types