Black Women Need Genetic Testing for Breast Cancer Too

Study shows genetic counseling and tests are key for Black and White women to predict the risk for developing breast cancer.

Researcher: Julie Palmer, ScD
Institution: Trustees of Boston University
Area of Focus: Population Science
Grant Term: 1/1/2018 to 12/31/2021

“Black women who participate in the American Cancer Society’s Cancer Prevention Study-3 and Cancer Prevention Study-II and who supplied blood samples were part of this important research.
“This study provides evidence to promote health equity in genetic counseling and testing to help determine the risk of developing breast cancer. Our CPS-II and CPS-3 participants’ willingness to donate their time and information contributed to this pivotal finding, which could improve the lives of many Black women in the future by reducing disparities in breast cancer care and outcomes.”—Lauren Teras, PhD, Scientific Director and lead for breast cancer research, Population Science, American Cancer Society

The Challenge: In women with ancestors from Europe, at least 10 gene mutations, in addition to BRCA1 and BRCA2, have been associated with an increased risk of breast cancer. Yet, there’s limited data about genetic risks in women with ancestors from African, including African American (AA) women.

Knowing about genes and family history allows researchers and doctors to help guide women in making informed decisions to manage their risk of developing breast cancer. For example, women with a high risk may be counselled about the option to have prophylactic surgery to remove the breasts or may have a need for an enhanced screening plan for the early detection of breast cancer by having more frequent mammograms or having MRIs to screen for breast cancer.

Understanding genetic factors also helps guide treatment for women who develop breast cancer.

Some expert groups have developed guidelines for when genetic counseling and possible testing for breast cancer-related gene mutations should be considered, but they are complex and not all doctors agree with them.

Genetic testing, counseling, and treatment refinement could be particularly beneficial for AA women. AA women have a higher incidence of breast cancer before age 50, a higher incidence of estrogen receptor (ER)-negative breast cancer and triple-negative breast cancer, a more frequent family history of ovarian cancer, and a 42% higher breast cancer death rate than White women. Yet, doctors are less likely to refer Black women for breast cancer genetic counseling and testing than they are to refer White women.

Without more data, it’s still unclear if there are racial differences in inherited mutations in breast cancer predisposition genes. It’s also not clear how or if someone’s race should inform strategies for genetic counseling and testing.

Inheriting Cancer Risks: Some Basic Terms

Permanent changes in the DNA sequence of a gene are called gene mutations. Some scientists think that “gene variant” is a more accurate term because changes in DNA do not always lead to disease. Sometimes they’re used as synonyms.

Genetic variants can have a large or small effect on the likelihood of developing a particular disease. The term “pathogenic” refers to something that causes a disease. When genetic variants lead to disease, they’re called pathogenic variants, or pathogenic mutations.

Genes that are vulnerable to cancer-causing variants or changes are called cancer-predisposition genes. In some cases, a cancer-predisposition gene is inherited, or passed along from generation to generation. Several dozen cancer-predisposition genes have been identified, and about 5 to 10% of all cancers result directly from those that are inherited from a parent.

For example, BRCA1 and BRCA2 are inherited cancer predisposition genes. Mutations on these genes increase the risk for developing certain cancers.

People who inherit certain changed genes that make them more likely to develop cancer are said to have a genetic predisposition or a genetic susceptibility to a cancer or certain types of cancer. Sometimes this is referred to as having a family cancer syndrome. But having this doesn’t mean that person will develop cancer. And if they do develop cancer, it may not be caused by the inherited genetic mutation.

The Research: To help fill this knowledge gap, the United States-based Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium reviewed data from 5,504 AA women with breast cancer and 4,993 AA women without breast cancer from 10 epidemiologic studies (including the American Cancer Society (ACS) Cancer Prevention Studies, CPS-II and CPS-3).

The consortium recently published results from this first large study aimed at identifying breast cancer predisposition genes in an African ancestry population. It provides the first estimates about the risk of breast cancer in women of African ancestry based on mutations in predisposition genes other than the genes BRCA1 and BRCA2. This study was partly funded by the American Cancer Society.

The researchers looked in the data from AA women for pathogenic mutations in the 12 genes associated mostly with European ancestry. They found that:

For AA women overall

  • Pathogenic mutations previously identified in White women are also highly predictive for developing breast cancer in Black women.
  • Among the 23 genes tested in this study, pathogenic mutations were identified in 8% of AA women who had breast cancer and 2% who did not.
  • Mutations in BRCA1, BRCA2, and PALB2 were linked with high risks of developing breast cancer.
  • Mutations in the genes CHEK2, ERCC3, and RECQL were linked with moderate risks for developing cancer.

This study estimates that Black women with mutations in the gene PALB2 have a 58% lifetime risk of developing breast cancer (by age 85 years). The lifetime risk of breast cancer for women with BRCA2, CHEK2, and ATM are 48%, 30%, and 21% respectively.  

For AA women with ER- breast cancers (including triple-negative breast cancers)

  • Frequency of pathogenic mutations was especially high (10%) in AA women with ER- breast cancer.
  • Mutations in the genes BRCA1, BRCA2, PALB2, and RAD51D were linked with a high risk of ER- breast cancer.
  • Mutations in genes BRCA1, PALB2,and RAD51D were more strongly associated with ER- than ER+ breast cancer.

For AA women with ER+ breast cancers

  • Mutations in genes CHEK2, ATM, ERCC3, and FANCC were only associated with ER+ breast cancers, but only at a moderate risk level.
  • Mutations in genes BRCA1 and PALB2 were associated with ER+ breast cancer but not as strongly as they were with ER- breast cancers.

 The lead author of the published study was Julie Palmer, ScD, an American Cancer Society (ACS) research grantee. Some of the many other contributors included former ACS grantees Jeffrey N. Weitzel, and Fergus Couch, PhD, (senior author), and former ACS epidemiology researcher, Mia Gaudet, PhD.

In a follow-up study, members members of the CARRIERS consortium looked for racial differences in the prevalence of pathogenic mutations in breast cancer predisposition genes between US Black and White women.

They found that the prevalence of pathogenic mutations in 3 genes— BRCA2, CHEK2, and PALB2—was higher in Black women, but they noted that the differences were small. The authors concluded that there was not sufficient evidence to make changes to currently available genetic testing guidelines based on race alone. This is because the current guidelines already account for the fact that Black women are diagnosed with breast cancer at a younger age than White women, more often have triple-negative breast cancer, and more frequently have a family history of ovarian cancer.

This second study used CPS-II as part of the reviewed data and its authors again included former grantees Drs. Couch and Palmer.

Why Does It Matter? There have been some misconceptions that breast cancer genetic counseling and testing is not applicable to Black women. The first study’s findings demonstrate that learning whether a woman has mutations in certain cancer predisposition genes is, in fact, highly predictive of the development of breast cancer in Black women.

In the second study, the authors’ note that Black women are less likely to undergo breast cancer genetic testing than White women, largely owing to differences in physician recommendations or access to care. The CARRIERS’ authors advise health care professionals make continued efforts to reduce barriers for genetic testing for Black women and ensure equal access and uptake of genetic testing to minimize disparities in care and outcomes based on race.