In Women With Breast or Ovarian Cancer, Pathogenic Gene Variants Linked With Increased Survival

By Lorraine L. Janeczko

August 30, 2021

NEW YORK (Reuters Health) - Women with breast or ovarian cancer and BRCA1/2 or other pathogenic gene variants may be equally or less likely than non-carriers to die from their cancer in the short term, according to a population-based study.

"This is reassuring. Patients often worry that having inherited genetic risk means they are more likely to die of their cancer. Instead, they are less likely to die," said lead study author Dr. Allison W. Kurian of Stanford University School of Medicine, in California.

"These findings will help oncologists counsel patients about the likely outcome of their cancer, and reassure them that having an inherited genetic mutation is, if anything, a good prognostic factor," she told Reuters Health by email. "This information will also help patients feel less apprehensive about having a genetic test."

Dr. Kurian and her colleagues examined Georgia and California Surveillance Epidemiology and End Results (SEER) registry records that were linked to results of gene tests. Women included in the study had stages I-IV breast cancer or ovarian cancer diagnosed between 2013 and 2017, received chemotherapy.

The researchers analyzed data from more than 22,000 breast- and 4,300 ovarian-cancer patients, with a median follow-up of 41 months. Pathogenic variants (PVs) were present in 12.7% of breast cancer patients with estrogen- and/or progesterone-receptor-positive, HER2-negative cancer; 9.8% of patients with HER2-positive cancer; 16.8% of those with triple-negative breast cancer; and 17.2% with ovarian cancer.

As reported in the Journal of the National Cancer Institute, the researchers used multivariable Cox proportional hazard models to examine the link between genetic results and cancer-specific mortality.

In triple-negative breast cancer patients, cancer-specific mortality was significantly lower with BRCA1 (hazard ratio, 0.49) and BRCA2 PVs (HR, 0.60), while the difference was not significant for other PVs (HR, 0.65), compared with non-carriers.

In ovarian cancer patients, cancer-specific mortality was also significantly lower with PVs in BRCA2 (HR, 0.35) and genes that were not BRCA1/2 (HR, 0.47). The researchers found no PV linked with higher cancer-specific mortality.

"This is the largest, most representative study of women diagnosed with breast cancer or ovarian cancer and tested for inherited gene mutations - not just in the BRCA1 and BRCA2 genes, but in many other commonly tested genes including ATM, CHEK2 and PALB2," Dr. Kurian said.

"Prior studies suggested that patients with inherited mutations in genes such as BRCA1/2 may be more responsive to chemotherapy because of their cancer's reduced ability to repair damaged DNA, so it makes sense that these patients might have better survival - and our study confirmed that they do," she explained. "This is not surprising, but it is important to have solid evidence from a large, diverse, contemporary sample that represents the U.S. population."

Dr. Stephanie Wethington, an assistant professor of gynecology and obstetrics and the director of The Susan L. Burgert, M.D. Gynecologic Oncology Survivorship Program at Johns Hopkins Medicine in Baltimore, Maryland, said, "What we should all take away from this study is the critical importance of genetic testing for all individuals diagnosed with an epithelial ovarian cancer."

"Identifying these mutations is critically important for treatment decisions regarding an individual with an epithelial ovarian cancer and for prevention in family members who may be carriers," she told Reuters Health by email.

"A recent publication showed that only approximately 30% of women with epithelial ovarian cancer undergo genetic testing," cautioned Dr. Wethington, who was not involved in the study. "This is a major lost opportunity for prevention of a cancer that, despite new encouraging treatments, remains deadly."

Elisabeth McCauley King, the executive director of genomics and precision medicine at City of Hope Comprehensive Cancer Center in Duarte, California, commended the authors on the study design.

"Utilizing statewide cancer registries allowed the authors to avoid the selection bias inherent in studies that use data from individual institutions, and the study appropriately included a diverse cohort of women," she said.

"This is incredibly important information for clinicians," King, who also was not involved in the study, told Reuters Health by email. "With their patients and patients' families, clinicians can consider the trade-off between risks and benefits associated with particular treatment strategies, based on each patient's values."

Dr. Kurian's research team plans to continue their investigation in patients with other cancers.

SOURCE: Journal of the National Cancer Institute, online August 9, 2021.