The DNA damage repair landscape in Black women with breast cancer

By Svasti Haricharan

Black people have the highest cancer mortality rate of any racial or ethnic group. Among Black women, breast cancer makes up about a third of all cancer diagnoses, with ER+ breast cancer being the most common. Black women with ER+ breast cancer are 42% more likely to die of the disease than white women.

This study examined gene expression in breast tumor and normal samples from 185 Black patients and compared them to samples from white women, revealing significant molecular differences in DNA repair in breast tissue that could help explain why more Black women die from ER+ breast cancer. The work suggests that addressing the disparity could be as simple as changing the timing of existing breast cancer treatments for Black women.

DNA repair is a fundamental part of normal cellular function, regulating processes throughout the cell and helping them recover from the errors that occur naturally during DNA replication or in response to external factors like stress. Unlike healthy cells, cancer cells often acquire molecular changes that make their DNA repair inefficient, which can make these cells resistant to treatment.

The study found that eight genes powering DNA repair are expressed differently in tumors from Black women when compared to those from white women. It also found consistent molecular differences in the cellular signals controlling how fast cells can grow. Notably, these differences were not confined to cancer cells—even healthy tissue showed a different gene expression pattern in Black versus white women, suggesting that the observed differences are fundamental to the way Black women respond to cancer and cancer treatment.

In addition to these implications for molecular biology, the study provides a real-world example of how precision medicine for ER+ breast cancer could be quickly and easily improved by taking patient demographics into account. Specifically, the study suggests that Black women could benefit from earlier intervention with CDK inhibitors, drugs that help stop cancer cells from multiplying by blocking biochemical signals called cyclin-dependent kinases (CDKs).

Current clinical guidelines for the use of CDK inhibitors suggest that they be used only after seeing progress in standard endocrine therapy, which means that for some women, by the time they receive CDK inhibitors, their disease has progressed too far.

However, this study found that there are significantly higher levels of one type of CDK in the tumor tissue of Black women, suggesting that at least a subset of Black women may benefit from earlier treatment with CDK inhibitors.

In a broader sense, the study highlights the critical need for more inclusive biomedical research that understands and respects the need for representing the unique biology of each patient when building datasets and forming hypotheses to test in the lab, rather than treating white tissue as the default.

Due to longstanding cultural barriers, including institutional biases and mistrust of the medical community, Black people are significantly underrepresented in tumor datasets and in clinical research in general. This means that the vast majority of current clinical guidelines were formed based off of data from a single racial group – white people.

While a single study like this is not enough to comprehensively address this issue, or wider racial health disparities, it does provide us with a way to move forward. Future directions for this work will include building a larger, more inclusive dataset of breast cancer tumors and using this to refine our results and ensure better precision medicine for Black women and, over the long term, for all underserved populations.

Article details

The DNA damage repair landscape in Black women with breast cancer
Aloran Mazumder, Athena Jimenez, Rachel E. Ellsworth, Stephen J. Freedland,Sophia George,
Matthew N. Bainbridge, Svasti Haricharan
First Published: February 8, 2022
DOI: 10.1177/17588359221075458
Therapeutic Advances in Medical Oncology

About the Author

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Svasti Haricharan received her B.Sc. from Stella Maris College in Chennai, India, her M.Sc. from the University of Leicester, UK and her Ph. D. in Molecular and Cellular Biology from Baylor College of Medicine. Haricharan completed two years of postdoctoral training at MD Anderson Cancer Center studying the effect of mutation load on breast cancer, before moving to Baylor College of Medicine for her second postdoctoral position focused on breast cancer genomics, where she was promoted to Research Assistant Professor. In October 2018, Haricharan joined the faculty at Sanford Burnham Prebys as an Assistant Professor in the Tumor Microenvironment and Cancer Immunology Program, where her work focuses on the role of DNA damage repair genes in breast cancer.