August 4, 2017
A higher proportion of aggressive breast cancer subtypes are seen in black women, according to a study led by a UNC Gillings School of Global Public Health researcher. The study findings help to explain a gap in mortality that exists between black and white women with breast cancer and could lead to improved treatment approaches to help close that gap.
Published Aug. 1 in the Journal of the National Cancer Institute, the study reported analyses of about 1,000 invasive breast tumors and confirmed that young black women are more likely to have “triple negative,” or “basal-like,” breast cancers, a subtype that does not express any of the receptors for targeted biologic therapies.
The study also identified variation by race within a clinical breast cancer type that has the greatest mortality disparity. Specifically, the researchers found that younger black women with hormone-receptor positive, HER2-negative breast cancer were more likely to have a high risk of recurrence score.
“When we look at a more clinically homogeneous group, such as women who have hormone-responsive, HER2-negative disease, we see pretty significant and biologically important differences between black and white women,” said the study’s lead author Melissa Troester, PhD, professor of epidemiology at the Gillings School and member of the UNC Lineberger Comprehensive Cancer Center. “With genomic information, we’re better able to say which patients are likely to have indolent – or slow-growing – disease. And right now, we might mistake some people as having indolent disease, when actually they have a more aggressive tumor.”
The research was part of the third phase of the seminal Carolina Breast Cancer Study (CBCS), a population-based study launched at UNC-Chapel Hill in 1993. A driving motivation for the work has been to understand why African-American women disproportionately die from breast cancer. Since 1993, CBCS has gathered data on more than 8,000 women from 44 counties in North Carolina.
In the new study, researchers compared the findings of commonly used immunohistochemical tests, which classify breast cancer according to tumor markers, with the findings of the PAM50 gene expression assay, which classifies tumors into different risk groups as well as different molecular subtypes based upon each tumor’s genomic characteristics.
Confirming previous findings, researchers found that black women were diagnosed less frequently with luminal A breast cancer, a subtype of breast cancer that has a better prognosis overall. Black women had significantly higher odds of all three non-luminal A breast cancer subtypes. Their odds of basal-like breast cancer, a particularly aggressive subtype, were three times higher compared to white women; odds were 45 percent higher for luminal B breast cancer for black women, and odds were twice that of white women for HER2-enriched breast cancer.
“If you look at the group of basal-like breast cancers, the burden of this disease is much higher if you’re young and black,” said UNC Lineberger’s Lisa A. Carey, MD, physician-in-chief of the N.C. Cancer Hospital and study co-author. “We believe this is playing a role in racial disparities in outcomes between young and old, and black and white women with breast cancer.”
The researchers also found variation within a clinically defined subtype – in particular, the hormone-receptor positive, HER2-negative subtype. Hormone receptor-positive, HER2-negative breast cancer has the best prognosis overall, but the researchers report mortality disparities are also greatest within this group.
In both black and white women, hormone receptor positive, HER2-negative breast cancer tumors sometimes were classified into the more aggressive genomic subtypes, including as basal-like breast cancer. Black women’s tumors also were classified more often into aggressive subtypes; within this group, there also was higher risk of recurrence scores.
The findings underscore the role of genomic testing to drive precision medicine approaches to treatment and may help explain a disparity in survival for black women with this type of breast cancer. In addition, the findings could have important clinical implications. Black patients with higher risk of recurrence scores could be candidates for chemotherapy or new treatment approaches, as high-risk scores are an indication for chemotherapy.
“If a woman really has a luminal A, low-risk tumor, and she was hormone receptor-positive and HER2-negative, she could be treated less aggressively and have different surgical options,” Troester said. “But if she had these other tumor genomic subtypes, her doctor might consider a more aggressive treatment plan. We can do better to distinguish aggressive and indolent cancers if we use the genomic data that is becoming available.”
Other Gillings School co-authors include Xuezheng Sun, PhD, research assistant professor of epidemiology; Emma H. Allott, PhD, research assistant professor of nutrition; Chiu-Kit (Jessica) Tse, MSPH, applications specialist in epidemiology; Whitney R. Robinson, PhD, assistant professor of epidemiology; Erin L. Kirk, research specialist in epidemiology; and Andrew Olshan, PhD, Barbara Sorenson Hulka Distinguished Professor in Cancer Epidemiology and chair of the epidemiology department.
Additional UNC co-authors are Charles Perou, MD, distinguished professor of genetics; Joseph Geradts; Stephanie M. Cohen, research associate at UNC Lineberger; Leigh Thorne, clinical professor of pathology laboratory medicine; Michelle Matthews, MD, associate professor of obstetrics and gynecology; Yan Li, PhD, research specialist at UNC Lineberger; Zhiyuan Hu, PhD, scientific director of the Microarray RAM Lab at UNC Lineberger; Katherine A. Hoadley, PhD, research assistant professor of genetics; Katherine E. Reeder-Hayes, MD, MBA, clinical assistant professor of oncology; and H. Shelton Earp, MD, Lineberger Professor of Cancer Research and director of UNC Cancer Care.
Olufunmilayo I. Olopade, MD, of the University of Chicago, is also a co-author.
The study was supported by the National Institutes of Health and the National Cancer Institute.
This article originally was published on the UNC Lineberger website.