Mark E. Robson, MD
Population-based cancer screening using genetic sequencing technology is an idea worthy of careful consideration, but there are many challenges to implementing such a program, according to Mark E. Robson, MD, a Miami Breast Cancer Conference faculty member who specializes in the identification and management of people who have inherited an increased risk for cancer.
A gene mutation such as BRCA1/2
that predisposes a woman to breast or ovarian cancer, for example, “may not manifest itself until it causes cancer in a young person,” Robson said in an interview. “So, the argument is that if we test everybody and find those who have mutations, we will potentially be able to intervene early. This now becomes a potential public health benefit.”
Yet Robson, who serves as director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center, sees many challenges in population-based testing for BRCA
mutations. He explored these considerations in a presentation at the 32nd Annual Miami Breast Cancer Conference, held February 26-March 1 in Miami Beach, Florida.
“There is a conversation that’s taking place right now about whether there should be broader BRCA
testing offered to people who don’t necessarily meet any particular criteria, family, or personal history, and the rationale for that is that there are a number of people who have BRCA
mutations inherited from their father or who come from families where there is limited information,” Robson said in the interview.
The role of BRCA
genetic screening entered the popular imagination in May 2013 when actress and director Angelina Jolie announced that she had undergone a double mastectomy based on the discovery that she had a BRCA1
mutation that significantly increased her likelihood of developing breast and ovarian cancer. Jolie has a family history of ovarian cancer, but many other women with mutations do not have a history that would prompt testing.
Whereas the average woman in the United States has a 12% lifetime risk of breast cancer, BRCA1/2
carriers have at least a 50% to 60% lifetime risk.1
Female carriers of BRCA1/2
mutations have an even higher risk of developing ovarian cancer—over 40% among BRCA1
carriers and nearly 20% among BRCA2
carriers, up from a 1.4% chance in women without the mutations.1
Prophylactic mastectomy reduces the chances of developing breast cancer by over 90%, and preventive salpingo-oophorectomy substantially reduces the risk of ovarian cancer, which is hard to detect by screening.Screening Selected Populations
Large-scale population-based genetic test screening may not be practical because of issues of cost and complexities of interpretation. But it may be feasible for groups that have an increased chance of carrying a more limited range of mutations, said Robson, noting the Ashkenazi Jewish population (Jewish individuals of Eastern/Central European origin), of whom 1 in 40 carry one of three specific BRCA1/2
A study performed in Israel found that population-based testing had merit not merely because of the prevalence of BRCA
mutations among Ashkenazi individuals but also because the cancer risk among female carriers in that group increases dramatically with age.2
For Jewish Ashkenazi women, the cumulative risks of developing either breast or ovarian cancer by age 60 and 80 years, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1
carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2
carriers, according to the study.
“High cancer risks in BRCA1
mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the (Ashkenazi) population,” the report said. “General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria.”
The study also suggested that an Ashkenazi population screening could serve as an investigative model for evaluating the genetic predisposition to cancer in other populations.
“It is an interesting step in the evolution of a genetic susceptibility testing from an almost boutique type of analysis with nothing but a personal utility, which was what it was back in the 1990s, now to something that is potentially so clearly clinically useful that it should be offered to everyone,” Robson said.Prominent Researcher Ignites Debate