Researchers aim to identify factors that increase breast cancer incidence, mortality in black women

The NCI awarded a $12 million grant to investigators at Vanderbilt-Ingram Cancer Center, University of Southern California and Boston University to help launch a cancer research consortium to better understand the biology and genetics of breast cancer among black women.

Investigators will share, gather and analyze data from 18 previously published studies to develop a “big picture” assessment of 20,000 women with breast cancer and a similar number of controls.

Damali Martin

Wei Zheng

The researchers hope to identify prevention and treatment measures for this population — which is at higher risk for late-stage disease and breast cancer death — by identifying how genetic variants affect major breast cancer biological pathways. They also hope to determine differences between black women and white women.

Damali Martin, PhD, program director for the epidemiology and genomics research program of the division of cancer control and population sciences at NCI, and Wei Zheng, MD, PhD, MPH, director of the Vanderbilt Epidemiology Center and lead investigator on the study, spoke with HemOnc Today about how the investigation came about and the importance of analyzing these data.

Question: How did the idea for this study come about?

Martin: Historically, it has been difficult to pursue these types of studies in minority populations, because the number of minorities who participate in studies is quite low. For these 18 studies, the cohorts were very small. The success of each of these smaller studies, and the information we got out of them, was very limited. For this current study, investigators gathered together with the encouragement of the NCI to share data and samples in order to create one large study.

Zheng: First, black women have a higher risk of dying of breast cancer than white women. Black women have a high risk of developing triple-negative breast cancer, and we are unsure why. Factors such as the environment or genetics could explain the elevated risk for breast cancer. There are no targeted therapies for the triple-negative breast cancer type, which is defined as ER negative, PR negative and HER-2 negative. Prognosis is not good and survival rates are low. Second, many genetic studies have been conducted in European and Asian descendants, whereas the sample size of these types of studies conducted in black women is quite small. So far, we do not know much about the genetic risk factors in black women. Third, the African genome is very informative, as it is far more heterogeneous compared with European and Asian populations. Thus, we should be able to gain substantial knowledge by conducting genetic studies in African-ancestry populations.

Q: Why is there a need to generate the data?

Martin: The cause of breast cancer and the disparities that exist for breast cancer in black women are related to both social and genetic or biological risk factors. There are gaps in the knowledge of how these factors influence breast cancer risk —not only individually, but how they interact together to influence the overall risk in black women. This particular project will focus primarily on the genetic or biological risk factors, but further down the line we also will examine how these risk factors interact with the environment by combining demographic data, such as one’s neighborhood and other environmental risk factors. Another important aspect is that the data generated will be available as a shared resource for the research community. This will help us understand how all of these risk factors work together to increase the risk for breast cancer among black women.

Q: How will the data be gathered and analyzed?

Martin: Each of the 18 studies collected genetic and epidemiologic data. Investigators involved with the current study will combine all of these data into one specific larger study.

Zheng: We will not recruit any new participants, because the funding is not enough for new recruitment. We talked to the investigators who conducted these 18 studies, and we put together a consortium in which all of these investigators have agreed to contribute their data, which will include DNA samples as well as clinical and risk factor data.

Q: Why were the se 18 studies chosen?

Martin: These 18 studies focused on the genetic etiology of breast cancer in black women. They had all previously examined the role of genetics in breast cancer risk and, although the investigators were able to gain some insight, their success was limited due to the small sample size. By combining the data from all 18 studies, we are able to create a much larger study with enough women to give a comprehensive assessment of what genetics in breast cancer looks like in this population.

Q: What is your ultimate hope for the study?

Martin: This study will definitely increase our knowledge of the role that genetics plays in breast cancer risk in black women. Hopefully, we will be able to use the data on genetic factors to identify women who are at high risk for breast cancer. By doing this, we will be better able to manage their risk through prevention and screening efforts.

Zheng: We are confident that we will accomplish several things. For one, we will identify genetic risk factors for breast cancer among black women. We will use these data to build a risk-prediction model, along with other risk factors for breast cancer. We can use this model to identify high-risk women for prevention measures and, therefore, reduce their risk for breast cancer. Secondly, we hope to identify a novel gene pathway to help us understand the biology of breast cancer — particularly triple-negative breast cancers in African descendants — and then try to explain the reason for the disparities in cancer incidence and mortality. Thirdly, hopefully some of these novel genes can serve as a target for treatment in the future.

Q: After this study is complete , what is next on the research horizon ?

Martin: This study will focus on genetics, but other data will be collected — for example, data on the environment, treatments and on other exposures that increase breast cancer risk. Researchers will be able to look at how the genetic makeup interacts with other factors within the environment to drive breast cancer forward.

Zheng: This study will generate a lot of resources, because we will sequence the data from about 1,800 African descendants through whole-genome sequencing. We will share these data with the research community so that others may use it for genetic research — not only for breast cancer, but for other diseases, as well. Other studies, like the new phase 2 study by Lynce and colleagues that is set to evaluate the safety of palbociclib (Ibrance, Pfizer) for breast cancer in black women, are the exact type of research that we need. Black women are at higher risk for dying of breast cancer than white women. It is important to conduct studies to identify optimal therapies for this disease in black women.

Q: Is there anything else that you would like to mention?

Martin: This $12 million investment, in combination with previous investments, will continue to push this research area forward and will help us understand both the social and biological risk factors that contribute to disparities of breast cancer in black women. This study would not be possible without the strong collaboration and sharing of data and biospecimens, which is one of the priorities under Vice President Joe Biden’s national cancer moonshot initiative. As we move toward other research priorities, such as precision medicine, it is important that every person — regardless of their background — has the opportunity to benefit from these types of research advances. – by Jennifer Southall

For more information:

Damali Martin, PhD , can be reached at National Cancer Institute, BG 9609 MSC 9760,
, Bethesda, MD, 20892-9760; email: ncipressofficers@mail.nih.gov.

Wei Zheng, MD, PhD, MPH, can be reached at Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, 2525 W. End Ave., Suite 800, Nashville, TN 37203-1738; email: wei.zheng@vanderbilt.edu.

Disclosure: Martin and Zheng report no relevant financial disclosures.