The incidence of BRCA1 and BRCA2 mutations is higher in the Ashkenazi Jewish population and hence studies on population screening have initially been done in Israel. This week we celebrate the Jewish New Year…and the latest JAMA article on population based screening for these mutations was most timely.
The article published in the September 17 JAMA is based on the 2014 Lasker Award. This award in medical science was presented to Dr. Mary-Clair King to recognize and honor her “for bold and imaginative contributions to medical science and society – exemplified by her discovery of a single gene BRCA1 that causes a… form of hereditary breast cancer…” The article both describes the application of this discovery and suggests that population-based screening of women for BRCA1 and BRCA2 should become a routine part of clinical practice.
Just to remind you: BRCA1 mutation carriers have a combined risk of developing either breast or ovarian cancer of 60% by age 60 and 83% by age 80. For BRCA2 mutation carriers, risk is 33% by age 60 and 76% by age 80.
A recent study in Israel recruited more than 8000 healthy Ashkenazi Jewish men. The men were tested as a gateway to families for breast and ovarian cancer. (The men were unaffected by breast-cancer themselves but if they were positive, it would enable researchers to identify female mutation carriers, not based on their personal or family history of cancer.) 175 men were identified as carriers of the mutation and genetic testing was offered to all of their female relatives. Surprisingly, 50% of families found to harbor BRCA1 or BRCA2 mutation had no history of breast or or ovarian cancer that would have triggered clinical attention. However, female mutation carriers from these theoretically low-cancer- incidence families had similar cancer risks to female carriers from families with high cancer incidence. Low-cancer-incidence families were simply smaller with fewer females and hence were less likely to exhibit a significant breast or ovarian cancer history.
The authors of the article point out that without population-wide screening, women with BRCA1 or BRCA2 mutation from such families would not have been identified until they developed cancer; a failure of cancer prevention. This study has significant implications for preventive care in Israel which has a large population of Ashkenazi Jews. But in another study, it was found that only 35% of families with high incidence of breast or ovarian cancer had even previously been referred for genetic counseling, despite common knowledge of the increased risk due to BRCA1 and BRCA2 in the Ashkenazi Jewish population and the availability in that country of free testing and counseling.
In the United States, the number of carriers of mutations in the BRCA1 and BRCA2 genes is estimated to be between 1 in 300 and 500 women or between 250,000 and 450,000 adult women for whom breast and ovarian cancer is both highly likely and potentially preventable. Wide scale population genetic counseling and screening should go on our medical wish list. But at present, the US Preventive Services Task Force (USPSTF) supports BRCA1 and BRCA2 testing based on family history and ancestry, but not for the entire female population. Unfortunately only 19% of US primary care physicians accurately assess family history for BRCA1/BRCA2 testing. This is clearly unacceptable.
The author states at the end of the article that “population wide screening will require significant efforts to educate the public and to develop new counseling strategies, but this investment will both save women’s lives and provide a model for other public health programs in genomic medicine…. Women should have the choice to learn if they carry an actionable mutation in BRCA1 or BRCA2.” We have much to learn and do…