Molecular Differences in Breast Cells May Partially Explain Why Black Women Have Higher Breast Cancer Mortality
Breast cells in Black women repair damaged DNA differently from breast cells in white women — and sometimes not at all. This molecular difference may help to explain why Black women are 41% more likely to die from breast cancer than white women, according to a study.
The research was published on Feb. 8, 2022, by the journal Therapeutic Advances in Medical Oncology. Read “The DNA damage repair landscape in Black women with breast cancer.”
Black women and breast cancer
According to the American Cancer Society, breast cancer has become the leading cause of cancer death among Black women. Overall, Black women have a lower risk of being diagnosed with breast cancer than white women, but are 41% more likely to die from the disease.
Black women also are more likely to be diagnosed with triple-negative breast cancer than white women. Triple-negative breast cancer is:
Triple-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone receptor-positive or HER2-positive. Triple-negative breast cancers don’t respond to hormonal therapy medicines or medicines that target the HER2 protein.
Still, estrogen receptor-positive breast cancer is the most common type of breast cancer diagnosed in Black women. Additionally, estrogen receptor-positive breast cancer is more likely to be a higher grade and less likely to respond to standard-of-care hormonal therapy treatment in Black women than in white women. Research shows that Black women diagnosed with estrogen receptor-positive breast cancer have a 42% higher mortality rate than white women with the same type of breast cancer.
Many studies have tried to figure out why these differences exist. Research suggests a number of factors are involved, including access to healthcare, lifestyle choices, and environmental factors. Scientists have designed studies to account for all these factors, but still find differences in breast cancer outcomes between Black and white women diagnosed with estrogen receptor-positive breast cancer.
In this study, the researchers wanted to see if molecular differences in the healthy breast cells and breast cancer cells of Black and white women would help explain the differences in outcomes.
“The way each human being responds to cancer treatment is influenced by so many internal and external factors that are unique to each of us,” said senior author Svasti Haricharan, PhD, assistant professor at Sanford Burnham Prebys Medical Discovery Institute, in a statement. “The scientific community has to confront this and invest time and money into understanding it, because everybody deserves care that is tailored to their molecular makeup as closely as possible.”
About the study
The researchers analyzed datasets of genes from the:
breast cancer tumors of Black women and white women
healthy breast tissue of Black women and white women
The breast cancer datasets included information from 144 Black women and 703 white women.
The healthy breast tissue datasets included information from 26 Black women and 150 white women.
The researchers noted that Black women are not well represented in currently available breast cancer tumor datasets. Still, they felt it was possible to conduct an exploratory analysis looking for molecular differences in breast cancers in Black women, which could lead to more research in the area.
“Black women are severely underrepresented in virtually all datasets of patient tumors, so a lot of previous results about breast cancer only accurately reflect what’s happening to white women,” said Dr. Haricharan. “We hope our research will highlight the need to study cancer in different racial and ethnic groups more closely and improve outcomes for historically marginalized patients.”
Earlier research has suggested a link between problems with how a cell repairs DNA damage and hormonal therapy resistance in estrogen receptor-positive breast cancer. DNA carries genetic information in both healthy cells and cancer cells. Cells can develop DNA damage spontaneously or from exposure to specific things in the environment — too much sun, for example — that make DNA damage more likely to happen. But cells can detect and repair damage to DNA. If a cell doesn’t detect and repair damage to DNA, the cell can become cancerous.
So the researchers focused on the genes that repair DNA damage in healthy breast cells and estrogen receptor-positive breast cancer cells.
They found differences between Black and white women in the way eight DNA repair genes were expressed — in both healthy breast cells and in estrogen receptor-positive breast cancer cells. The researchers also found molecular differences in the signals controlling how quickly cells grow, again in both healthy breast cells and in estrogen receptor-positive breast cancer cells.
When genes are expressed, it means they’re working and making proteins or other molecules that control cell functions. When a gene isn’t expressed, it isn’t helping to control cell functions.
The researchers also found that breast cancer cells from certain Black women overexpressed the CDK2 gene. When this gene is overactive, it can make cells grow uncontrollably.
A class of medicines called CDK4/6 inhibitors are used to treat certain types of hormone receptor-positive, HER2-negative breast cancer. There are three CDK4/6 inhibitors used to treat breast cancer:
Ibrance (chemical name: palbociclib)
Kisqali (chemical name: ribociclib)
Verzenio (chemical name: abemaciclib)
CDK4/6 inhibitors work by interrupting the growth process of breast cancer cells.
The researchers reasoned that certain Black women diagnosed with estrogen receptor-positive breast cancer that overexpresses CDK2 might benefit from a CDK4/6 inhibitor earlier in the treatment process. Although this idea is intriguing, it needs to be tested in clinical trials before it’s recommended as a treatment option.
“What we’re seeing here is a tangible molecular difference in how these cells repair damaged DNA — a critical factor in the development of cancer — which affects how cells grow and reproduce in tumors,” said Dr. Haricharan. “We need to build better datasets so we can stop considering what we observe in white people as the default for all biology, which creates a fundamental inequity in biomedical progress.”
What this means for you
Although extremely interesting, these early results are based on information from a small number of Black women. More research is needed to see if the results stay the same for larger numbers of Black women.
This study’s results show that having more information on breast cancer in Black women can lead to more effective precision medicine. Researchers need genetic analyses of more breast cancer tumor samples from Black women to figure out which treatments work best for their unique situations.
It’s also important to know that, although you can’t change which genes your cells express or how your cells work, there are steps you can take to keep your breast cancer risk as low as it can be, including:
getting regular mammograms and breast clinical exams
not smoking and avoiding alcohol
exercising every day
eating a diet full of nutrient-dense, minimally processed foods and avoiding foods with added sugar and trans fats
maintaining a healthy weight
If you’re a Black woman who has been diagnosed with breast cancer, you can learn more about the importance of participating in a clinical trial.
Written by: Jamie DePolo, senior editor
— Last updated on April 5, 2022, 4:44 PM