When her mother was diagnosed with breast cancer, Sarah was too young to understand. Now, at age 32, she’s already started her breast screening. “I wanted to make sure that I would be around for my kids,” she said. “Who knows if I’ll ever get breast cancer? But, if I do, I want to catch it early.”
Even after the busy cancer awareness season of pink ribbons and fundraising walks comes to an end, cancer’s harsh reality remains. According to the American Cancer Society, there will have been an estimated 266,120 cases of breast cancer and an estimated 22,240 cases of ovarian cancer diagnosed in the U.S. in 2018. Last year according to the American Cancer Society, there were an estimated 40,610 deaths from breast cancer and an estimated 14,080 deaths from ovarian cancer in the U.S.
While breast and ovarian cancers are not believed to be any more common in the Jewish community, the Jewish community does have unique risk factors. Having information — and correcting misinformation around the topic — can help our Jewish community face the risks with strength and reason.
BRCA-related Hereditary Breast and Ovarian Cancer
The vast majority of cancer occurs sporadically and does not have a hereditary component. Only 5 to 10 percent of cancers have a hereditary component. For those with an inherited predisposition to breast cancer, the most common hereditary cause are gene mutations in the BRCA genes. We all have thousands of genes in the body, each with different functions. Hundreds of those genes are supposed to protect us from cancer, including the BRCA1 and BRCA2 genes. However, when there are mutations present in those types of genes, some of that protection is compromised. Therefore those with mutations in their BRCA genes have higher cancer risks (figure 1) and may develop cancer at younger ages than the average population.
The knowledge that one carries a BRCA mutation is not meant to be daunting. Instead, the purpose is to empower an individual or family to be proactive and take appropriate steps to either detect cancer at an early and treatable stage, or reduce cancer risks (figure 2). Additionally, reproductive options exist to help BRCA carriers avoid passing on the mutation to future generations.
Thanks to Angelina Jolie’s public acknowledgement of her BRCA carrier status and the United States’ Supreme Court decision regarding gene patenting surrounding BRCA, ruling that genes cannot be patented, (Assn. for Molecular Pathology v. Myriad Genetics Inc., June 2013) the summer of 2013 brought these genes to the forefront of public consciousness. Women throughout the world began to wonder if they should be pursuing genetic testing to assess for mutations in the BRCA genes and if they too would consider taking surgical risk-reducing measures, such as a mastectomy, in order to lower their breast cancer risk. In fact, the “Angelina Effect” increased in the number of women being evaluated for genetic screening for mutations in the BRCA genes.
While these mutations are not particularly common in the general population — occurring in 1 in 300 to 1 in 500 individuals (Gabai-Kapara E, 2014)— individuals of Ashkenazi ancestry face an increased risk. Certain mutations in the BRCA genes occur at a frequency of between 1 in 40 to 1 in 100 among Ashkenazi Jews (Roa BB, 1996, Metcalfe KA, 2013). This rate appears to hold true regardless of personal or family history of cancer. If an individual of Ashkenazi ancestry has a personal history of cancer, the risk of a BRCA gene mutation is even higher. BRCA mutations are a family affair — a carrier’s siblings, children parents, and extended family are more likely to be carriers as well. As a community, we need to start taking ownership of these statistics.
Where do Ashkenazi Jewish mutations come from?
The Jewish population remains of great interest to geneticists. This is due primarily to genetic similarities among Jews of Eastern European backgrounds, or Ashkenazi Jews. Genetic similarities developed over hundreds of years of this insular community growing, shrinking, and rebuilding. Specific mutations (called founder mutations), originally rare in the population, became more common over time as the population decreased and then rapidly rebuilt itself.
These “genetic bottleneck events” and the emergence of common ancestral mutations can potentially be traced back to historic catastrophes in the Jewish community, such as the destruction of the second Temple, the Crusades and the Black Death. In this way, founder mutations, or common ancestral mutations, in genes like BRCA originated. Interestingly, there is some evidence to suggest that there are shared, as well as different BRCA founder mutations present in Sephardic and Mizrachi populations as well. That is to say, this may not just be an “Ashkenazi” problem, but perhaps something the entire Jewish community should be attuned to.
Cancer Genetic Counseling
The presence of common BRCA mutations in the Jewish population makes the process of BRCA genetic testing very straightforward for Ashkenazi Jews. Genetic testing for hereditary cancers is best done in conjunction with the evaluation of a genetic counselor. Genetic counselors are medical professionals with training in clinical genetics and psychosocial counseling. In the context of genetic testing due to a personal or family history of cancer, a genetic counselor will appropriately interpret the results of genetic testing in the context of the cancer history.
Additionally, genetic counselors will assess the family history to determine that the appropriate genetic tests are ordered. If a BRCA mutation is suspected in an Ashkenazi family, the recommendation is to test for the three common Ashkenazi mutations first, and then to pursue more extensive BRCA genetic testing if those results are normal. Although mutations in the BRCA genes are the most common cause of hereditary breast and ovarian cancers, they are not the only cause; at times there are other genetic tests which should be offered.
Unfortunately, even among medical professionals, there are often misconceptions about cancer genetics risk assessment and recommendations for genetic testing. Some physicians have erroneously told their patients that a family history of breast cancer on their father’s side of the family is not significant. This is false, as we inherit half of our genes from each parent; males can be BRCA carriers, even though their overall cancer risks are lower than female BRCA carriers.
Ethnicity also plays an important role when it comes to risk assessment. The National Comprehensive Cancer Network’s clinical practice guidelines regarding hereditary cancers highlight the Ashkenazi Jewish population as “a population at increased risk.” Even a “weak” family history of breast or ovarian cancer in the context of Ashkenazi ancestry is concerning and may indicate a need for genetic testing.
To Test or Not to Test
The decision about whether or not to pursue genetic testing is a very personal one and should be made in consultation with one’s healthcare provider, family, and support system. For families that have seen multiple family members affected by cancer, information about genetic status can often feel overwhelming or scary.
The reality is that a family with a strong history of cancer is at increased risk for cancer whether or not they decide to pursue genetic testing. Genetic test results can, however, clarify the cancer risk for specific family members and provide medical options for carriers (figure 2). The availability of genetic testing is meant to feel empowering for an individual, not immobilizing.
This information can be used to protect future generations. Couples in which one member is a BRCA carrier can pursue in vitro fertilization with preimplantation genetic diagnosis (PGD), a process by which couples can choose to create embryos outside of the body, test the embryos for the specific mutation which runs in the family, and then only implant the embryos which do not carry the familial mutation, thereby significantly reducing the chances of passing on the mutation to future generations.
How will individuals, families, and the Jewish community handle this type of genetic information?
Women and families with cancer may be hesitant to pursue testing out of fear of stigmatization, among other concerns. If I am found to have a BRCA mutation, how will my children find shidduchim? What does halacha say about preventive elective surgeries? How will I be able to handle the guilt I might feel for passing on a mutation to my children and grandchildren? Rabbinical and communal leaders need to be able to address these questions. Rabbis can educate themselves about BRCA, its implications, and its impact on families; as well as know their limits, and when it’s appropriate to refer to a professional. Clergy are often at the first lines of speaking with a family where a family member may have been recently diagnosed with cancer, or where a family member has passed away from cancer. In addition to empathy and sensitivity, this is a unique opportunity to start the conversation about hereditary risk and encourage the family to speak with a genetic counselor, if they haven’t already. If 1/40- 1/100 Ashkenazi Jews carries a BRCA mutation, then multiple families in a given community/synagogue will be impacted by BRCA. This is a community issue. Rabbis and community leaders can familiarize themselves with resources that already exist in our communities, help raise awareness, encourage dialogue and discussion of family history, and help normalize rather than stigmatize the reality of cancer and cancer risk.
Thinking more broadly, if the carrier frequency is so high, shouldn’t all Ashkenazi Jews undergo BRCA testing? Screening on the population level for Ashkenazi genetic disease-causing mutations has already proven successful for diseases such as Tay-Sachs and familial dysautonomia, to name a few. “Population screening” for BRCA would involve promoting screening for the Ashkenazi mutations in the BRCA genes for all Ashkenazi individuals based on their ethnicity alone, rather than offering screening based on family history of cancer. The very idea of population screening for mutations in the BRCA genes in the Ashkenazi population has been suggested by the scientific community (King MC, 2014, Manchanda R, 2015, Wiesman C, 2017). The difference here is that testing in the general Ashkenazi population to determine BRCA carrier status would be done in order to provide information regarding one’s own health and cancer risk, while carrier screenings for diseases such as Tay-Sachs are done solely to provide reproductive options to couples at risk of having an affected child.
Studies in Canada, Israel, England, and the U.S. have supported the notion of BRCA population screening for the Ashkenazi Jewish population (Metcalfe KA, 2010, Manchanda R, 2015, Wiesman C, 2017) since it identifies carriers who would have otherwise gone undetected due to their lack of cancer histories and/or their lack of awareness. This type of genetic screening is cost effective and has the potential to save lives, proponents say.
On the other hand, what do BRCA mutations mean in the context of an individual with no cancer history? Data from a recent study in Israel (Gabai-Kapara E, 2014) suggest that cancer risk in BRCA carriers is the same, whether they have a family history of cancer or not. However, many researchers and physicians still believe that the cancer risk for these “low risk” women with a BRCA mutation is not clear-cut. Additionally, our genes can tell only part of the story. Although their cancer risks are higher, individuals with a BRCA mutation may never develop cancer.
For those families with no history of cancer, the decision to pursue BRCA testing can feel even more complicated. However, to quote Dr. Mary Claire King, “From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.” For low-risk families, knowledge of this “unexpected” mutation may enable proactive, rather than reactive measures.
The decision of whether or not to pursue genetic testing is both personal and multifaceted. However, the Jewish community needs to move the discussion of cancer and BRCA out from behind closed doors and into the public realm. Increased awareness and education will allow families to make the best possible choices, for ourselves and for future generations.
Special thanks to Dr. Nicole Schreiber-Agus for her contributions to this article.