Genomic Study Seeks Clues to Help Explain Breast Cancer Disparities

June 13, 2017, by NCI Staff

Using one of the largest collections of tumor samples from African Americans with breast cancer, researchers have surveyed the molecular characteristics in these tumors and compared them with those of white women with breast cancer.

The study results, which appeared in JAMA Oncology on May 4, confirmed previous findings that, compared with white patients, African American patients are diagnosed at a younger age and are more likely to develop aggressive subtypes of breast cancer, including triple-negative breast cancer and the basal-like subtype in particular.

But, after adjusting for differences in the frequency of different breast cancer subtypes, the researchers found that tumors from African Americans and whites were overwhelmingly more similar than different based on molecular features such as genetic alterations, the expression of genes and proteins, and the number of copies of certain DNA segments.

"The most important thing we learned from these samples is that there really were not a lot of differences in the molecular characteristics of breast tumors between blacks and whites, once we had accounted for differences in subtypes," said Olufunmilayo Olopade, M.D., of the University of Chicago, who co-led the study.

Genetic Variants

In the United States, African American women and white women develop breast cancer at similar rates, yet African Americans are more likely to die of the disease. One reason may be that aggressive molecular subtypes of the disease occur more frequently in African American women than in white women.

When the researchers analyzed germline DNA from the patients, they concluded that differences in the molecular characteristics between the breast cancers in African American and white patients appear to be determined in part by inherited genetic variants.

"We found that a fraction of the molecular features in breast tumors was different between the races, and it looks as though many of those features are determined by the germline," said coauthor Charles Perou, Ph.D., of the University of North Carolina Lineberger Comprehensive Cancer Center.

"The good news is that if the molecular features of tumors in women of different races are the same, then patients should receive the standard treatments based on their subtype, regardless of their race," Dr. Perou added.

Using The Cancer Genome Atlas

For the study, Dr. Olopade and her colleagues used tumor and germline DNA samples from 930 women in The Cancer Genome Atlas (TCGA) project, including 154 women of predominantly African ancestry and 776 of European ancestry.

This is the largest collection of breast tumors from African American women that has been characterized thoroughly using molecular and genetic tests, noted Jean Claude Zenklusen, Ph.D., director of the TCGA program office, which is part of NCI's Center for Cancer Genomics. He pointed out that the specimens were "convenience samples," which means they were readily accessible to researchers and may not be representative of the U.S. population.

To assess the characteristics of the tumors, the researchers identified genetic mutations and other alterations in tumor DNA that occurred during a woman’s lifetime, which are known as somatic changes. They also analyzed the expression of certain genes and proteins, counted the number of copies of certain DNA segments, and profiled patterns of DNA methylation.

"The beauty of The Cancer Genome Atlas is that we were able to perform six large-scale molecular assays on every sample," said Dr. Perou.

Estimating Survival

Another aim of the study was to consider racial differences in the molecular characteristics of breast cancers—as well as inherited genetic variants—in relation to survival.

With a median follow-up time of 29 months, race was not associated with overall survival. However, the analysis showed that African Americans with the basal-like subtype of breast cancer or triple-negative breast cancer "trended toward" a worse overall survival compared with whites in analyses of subgroups based on subtype.

African American women were more likely to have a worse prognosis than white women in all categories, including the most common types of the disease, such as estrogen receptor-positive breast cancer, Dr. Olopade noted.  

Collaboration and Data Sharing

"As researchers, we need to focus on why the racial disparity in breast cancer outcomes occurs," said Dr. Perou. "We know that some is due to the germline, but we need to investigate other factors—both genetic and non-genetic—that may play a role in the disparity."

Dr. Olopade agreed that more research is needed, but added: "This study gives us a roadmap for integrating genomic testing into the treatment of women with breast cancer to improve outcomes for patients."

"My hope," she continued, "is that through collaborations and data sharing among researchers—and by making it easier for minority populations to participate in research—we will improve outcomes for all patients and improve health equity."

The molecular data produced by this study are freely available, noted Dr. Zenklusen. "The scientific community can use the data to answer lots of questions in the years to come—as well as to generate hypotheses for future work," he said.