Genomic findings may help explain racial disparities in outcomes among patients with breast cancer, according to a study published in JAMA Network Open.1

The study showed that Black patients with metastatic breast cancer were less likely than their White counterparts to have actionable genetic variations.

According to researchers, these results suggest that the underrepresentation of Black patients in clinical trials has made it more difficult to discover mutations that can be successfully targeted in Black patients, and this contributes to the poor outcomes observed in Black patients with breast cancer.

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“Non-Hispanic Black women are nearly 40% more likely to die from breast cancer than non-Hispanic White women, despite lower incidence of the disease,” said study author Neha Goel, MD, of the University of Miami Sylvester Comprehensive Cancer Center in Florida.

With this in mind, Dr Goel and colleagues conducted what they believe is the largest study to date of racial differences in genomic profiles of cancer patients.

The study included 6652 patients with breast cancer who were treated from 2014 to 2020 and had complete clinical and next-generation sequencing data in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The researchers examined variation profiles of 642 genes by tumor type (primary or metastatic) and self-reported race. Of the 3557 patients with primary breast cancer, 83.8% were White, 9.2% were Black, and 7.1% were Asian. Of the 3095 patients with metastatic disease, 85.1% were White, 8.9% were Black, and 6.0% were Asian.

Genomic Differences

The results showed that, for primary breast cancer, TP53 variations occurred more often in Black patients (62.0%) than in White patients (37.2%; P <.001) or Asian patients (46.2%; P <.008).

Variations in CDH1 occurred more frequently in White patients than in Black patients for both primary breast cancer (14.5% vs 7.7%; P =.02) and metastatic disease (16.6% vs 9.9%; P =.04).

For metastatic breast cancer, genes with actionable variations occurred more often in White patients than in Black patients — 9.1% and 6.4%, respectively (P <.05). For instance, variations in PIK3CA were found in 35.5% of White patients and 26.6% of Black patients (P =.04).

The PIK3CA finding is particularly relevant, according to the researchers, because of phase 3 trial results with the PIK3CA inhibitor alpelisib.2 The study showed that alpelisib plus fulvestrant prolonged progression-free survival, compared with fulvestrant plus placebo, in patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Implications and Next Steps

As long as genome-wide association study populations are skewed toward predominately White and European patients, Dr Goel and colleagues argue, fewer actionable genomic variations will be discovered in minority populations, and treatment inequalities will persist.

“To make progress, we need to partner with clinical trial cooperative groups and hospitals to help make clinical trials readily available to our minority populations,” Dr Goel said. “This includes increasing the number of clinical trials offered at safety-net hospitals, which treat our most vulnerable and uninsured patients, who are also often minority populations.”

Dr Goel added that, although individual physicians cannot overhaul the majority of clinical trials alone, they can push for more sequencing of tumors in their minority patients.

“We need to increase minority enrollment in precision oncology by increasing next-generation sequencing of both primary and metastatic breast cancer to potentially identify actionable mutations in diverse populations since studies have historically underrepresented Black and non-White breast cancer patients,” Dr Goel said.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Goel N, Kim DY, Guo JA, Zhao D, Mahal BA, Alshalalfa M. Racial differences in genomic profiles of breast cancer. JAMA Netw Open. 2022;5(3):e220573. doi:10.1001/jamanetworkopen.2022.0573
  2. André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940. doi:10.1056/NEJMoa1813904