according to researchers.
Dr. Nicholas Boddicker
The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.
Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.
The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.
The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.
The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
Results may inform guidelines
National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.
“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.
He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
Current testing limits ‘ridiculous’
“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.
Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.
“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.
Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.
“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”
Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.
As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.