A look at how BCRF investigators are unraveling the role of family history, race, ethnicity, and more to improve breast cancer detection and prevention
Most people who develop breast cancer have no family history of the disease, but that’s not always the case. An individual’s family history, genetics, race, and ethnicity are all important factors that can contribute to their breast cancer risk.
This year, the Breast Cancer Research Foundation (BCRF) is investing more than $16.5 million in understanding the inherited causes of breast cancer. We are committed to defining how inherited mutations and race and ethnicity influence breast cancer risk. Armed with this knowledge, clinicians may be able to identify those at high risk and employ personalized interventions to improve breast cancer outcomes.
How researchers are improving our understanding of inherited breast cancer risk
Most breast cancers are spontaneous and not caused by inherited genetic mutations. However some people have a higher risk of developing breast cancer than the general population because of their family history. Understanding the genetic factors that can increase breast cancer risk is an important area of research that helps scientists and clinicians identify people who may benefit from earlier detection, personalized screening, and risk-reducing strategies.
Researchers are continuing to uncover how inherited breast cancer develops, including how specific genetic mutations lead to disease and how those discoveries can improve prevention and treatment approaches.
Through its investment in research, BCRF is supporting investigators who are studying inherited risk factors and the complex relationship between genetics and breast cancer outcomes. These discoveries are helping advance new approaches to risk assessment, screening, prevention, and targeted therapies for people at higher risk of breast cancer.
Understanding BRCA Mutations and Improving Outcomes
An estimated 10% to 15% of breast cancers are thought to be caused by inherited genetic variants that are passed from generation to generation through our DNA; changes in a person’s genetic code that severely affect the normal functioning of a gene. The most common and best-known genetic mutations associated with a higher risk of developing breast cancer are the BRCA1 and BRCA2 genes.
In landmark discoveries in the 1990s, BCRF investigators Drs. Mary-Claire King, Alan Ashworth, and their colleagues identified BRCA1 and BRCA2, respectively. These findings launched new avenues of research that propelled our understanding of hereditary breast cancer and led to the development of genetic testing that is in use today.
In the general population, about 12% of women in the U.S. will develop breast cancer in their lifetime. By contrast, about 72% of those with a BRCA1 mutation and about 69% of those with a BRCA2 mutation will develop breast cancer by the age of 80. In men with BRCA2 mutations, the risk of developing breast cancer increases to 8% (compared with 0.1% in the general population).
BCRF investigators are tackling BRCA1/2 mutations from every angle. They are devising ways to refine risk stratification for mutation carriers and to increase and optimize screening. In a 2025, BCRF investigator Dr. Fergus Couch led a large-scale study to improve risk assessment for BRCA2 mutation carriers. Not all gene mutations will lead to breast cancer. Dr. Couch’s study classified the risk conferred by over 7,000 BRCA2 gene variants of uncertain significance, which will allow for more personalized screening for these carriers. Research is enabling us to move beyond standard-of-care prophylactic surgery and enhanced surveillance to offer non-surgical preventative treatments, such as vaccines, in BRCA1/2 carriers. In carriers who are unfortunately diagnosed with breast cancer, researchers are also working to improve treatment outcomes and reduce the risk of recurrence through clinical trials that test the efficacy of existing drugs such as OlympiA and OlympiAD spearheaded by BCRF investigators.
Uncovering BRCA Mutations by Race and Ethnicity
Understanding hereditary breast cancer across diverse populations remains an important area of research, as inherited genetic mutations do not affect every population equally.
While BRCA mutations are relatively rare, certain populations have a much higher risk of inheriting one. In those with Ashkenazi Jewish (Eastern European) heritage, the chance of inheriting a BRCA gene mutation is 1 in 40, compared to 1 in 500 in the general population. In Jewish people of Ashkenazi descent, BRCA mutations are responsible for 10% of breast cancer and 40% of ovarian cancer cases.
In a groundbreaking project—the New York Breast Cancer Study—led by Dr. King, 1,007 Ashkenazi Jewish women with breast cancer were tested using a multi-gene panel. The team found that among this population, approximately 11% of all breast cancers are caused by one of only three BRCA1 or BRCA2 mutations, while 1% of those tested carried mutations in other known breast cancer genes (mostly CHEK2). This study supported screening in the Ashkenazi Jewish population and inspired BCRF investigators Drs. Domchek, Garber, Kenneth Offit, and Katherine Nathanson to develop and test a novel screening program in women and men with Ashkenazi ancestry in the U.S. to identify families at risk of breast and other cancers.
Less is known, however, about the prevalence of BRCA mutations in other populations, making this a research priority. BCRF investigators Drs. King, Ephrat Levy-Lahad, and Moien Kanaan have conducted genetic testing in over 1,700 breast cancer patients of Arab ancestry—the largest cohort of Arab women in the world to participate in cancer genetics testing. As a result of their BCRF-supported research, genetic testing and counseling is now routine for breast cancer patients at most major Palestinian hospitals.
Studies on breast cancer–associated genetic mutations have typically been conducted in white women, leaving a big question mark as to whether women of color are affected similarly. To address this disparity, BCRF investigators have led the way by conducting studies involving Black and Hispanic women.
- Dr. Olufunmilayo Olopade worked to mainstream genetic testing for BRCA1 and BRCA2 gene mutations and extend its use to Black women. This is particularly important, as Black women are disproportionately diagnosed with aggressive triple-negative breast cancer (TNBC), the most commonly diagnosed breast cancer in BRCA1 mutation carriers.
- Drs. Christine Ambrosone, Couch, Nathanson, Domchek, and colleagues examined the link between genetic mutations and breast cancer risk in Black women. Comparing genetic data from 5,054 Black women with breast cancer to 4,993 unaffected Black women, the researchers found that mutations in BRCA1, BRCA2, and other genes were associated with high and moderate risk of the disease in this population.
- In BCRF-funded studies, Dr. Jeffrey Weitzel developed a genomic cancer risk assessment tool to evaluate BRCA-associated breast and ovarian cancers in Hispanic women and Latinas. Through these studies, he discovered a distinct BRCA1 mutation that may have originated in Mexico.
Investigating Genetic Mutations Beyond BRCA
BRCA mutations account for only 5 to 10% of hereditary breast cancers. Through the aforementioned New York Breast Cancer Study, Dr. King and her colleagues showed that mutations in CHEK2 double a person’s risk of breast cancer—a significant increase, but not nearly as severe as the more than ten-fold increase due to BRCA1 or BRCA2 mutations.
Other work by BCRF researchers Drs. Offit, Couch, Mark Robson, James Ford, and their teams, has enriched our understanding of inherited risk, expanding it to include mutations in genes such as PALB2, BARD1, TP53, ATM, and others.
How researchers are identifying risk beyond family history
Dr. Couch has also led several large studies that yielded the first-ever estimates of breast cancer risk for women of different races and ethnicities with inherited gene mutations other than BRCA1 and BRCA2. In one study, his team, which included BCRF investigators Drs. Priyanka Sharma and Garber, assessed genes in more than 10,000 people with TNBC and found mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with a high risk of TNBC, while BRIP1, RAD51C, and TP53 mutations were associated with moderate risk. These results were similar in Black and white women.
Beyond identifying specific mutations, researchers are also studying how inherited risk factors influence people who may not have traditionally been considered high risk.
In early 2021, Dr. Couch and fellow BCRF investigators Ambrosone, Nathanson, and Domchek published the results of the first large study to examine inherited mutations in breast cancer susceptibility genes in women without a family history of the disease (previous studies had focused on high-risk populations). Analyzing DNA from 32,247 women with breast cancer and 32,544 unaffected women yielded several important insights. Among them:
- While the risk of developing breast cancer is generally lower for women without a family history of the disease, 30 to 50% of breast cancer mutations occur in women who have traditionally not been considered high risk.
- Although uncommon, specific gene mutations in the BARD1, RAD51C, and RAD51D genes were associated with an increased risk of estrogen receptor (ER)–negative breast cancer and TNBC and were more frequent in Black women.
- Mutations in ATM, CDH1, and CHEK2 were linked to an increased risk of ER-positive breast cancer and more frequent in non-Hispanic white women.
These studies are ongoing and will provide additional insights into differences in specific gene mutations associated with race as well as breast cancer subtype.
How genetic risk scores may improve breast cancer prevention
Investigators are also examining ways to leverage a person’s risk assessment score to more accurately define their level of risk. Known as a polygenic risk score, it is calculated by surveying an individual’s whole genome and summarizing the net effect of many genetic variants, which by themselves may not increase risk, but together can elevate an individual’s chances of developing diseases such as breast cancer.
Advancing hereditary breast cancer prevention and treatment
Research into hereditary breast cancer continues to uncover how inherited genetic mutations influence breast cancer risk and outcomes. By identifying new risk factors and understanding how different genetic changes affect disease development, researchers are working to improve how people at higher risk are identified, monitored, and supported.
These discoveries are helping shape the future of breast cancer care, from more personalized risk assessment and screening approaches to new prevention strategies and targeted treatments. As researchers continue to study inherited mutations beyond BRCA1 and BRCA2, they are uncovering new opportunities to improve outcomes for people with hereditary risk.
BCRF remains committed to funding the research needed to advance these discoveries. Through investments in genetics, prevention, and treatment research, BCRF investigators are helping build a future where hereditary breast cancer risk can be better understood and managed.
Support the research driving these discoveries. Donate, start a fundraiser, or explore other ways to give and help fund the science that is advancing our understanding of hereditary breast cancer, improving prevention strategies, and shaping the future of breast cancer care.
Frequently asked questions
Can someone have a BRCA mutation without a family history of breast cancer?
Yes. While a family history of breast or related cancers can increase the likelihood of an inherited mutation, some people with BRCA1, BRCA2, or other mutations do not have a known family history of breast cancer. Genetic counseling can help determine whether testing may be appropriate based on personal and family history.
How are researchers finding new genes linked to breast cancer risk?
Researchers use approaches such as genetic sequencing, large-scale population studies, and data from people with and without breast cancer to identify gene changes that may influence risk. These discoveries help scientists better understand how breast cancer develops and may lead to improved risk assessment, prevention strategies, and treatments.
Can inherited breast cancer risk be reduced?
People with inherited risk factors may have options to manage their risk, including enhanced screening, risk-reducing strategies, and conversations with healthcare providers about available interventions. Research continues to improve how doctors identify and support people with inherited risk.
