Prenatal testing helps identify mother's cancer risk

Harmful BRCA1 gene variants significantly increase your lifetime risk of developing breast, ovarian and pancreatic cancer, but most people don't know they are carriers.

In a new study published in the American Journal of Obstetrics and Gynecology, scientists from Weill Cornell Medicine, Columbia University Irving Medical Center (CUIMC) and NewYork-Presbyterian examined the possibility inclusion of BRCA1 testing during antenatal screening of carriers. Researchers have found that this approach is not only cost-effective, but can also identify people at increased risk at a time when cancer screening and other prevention strategies could save their lives.

Important point for testing mothers

Individuals who have inherited a variant of the BRCA1 gene have several options to reduce their risk of cancer, such as enhanced screening and surgery. However, most patients find out they are BRCA1 carriers only after they have already been diagnosed with cancer. One challenge is finding the time when genetic testing will have the greatest impact. Pregnancy and obstetric care may offer a unique window to screen and identify patients before they develop cancer.

"Many patients see their pediatrician as children, but when they become young adults, the next doctor they see may be their OB/GYN when they are pregnant," said Dr. Shayan Diun, a member of the Herbert Irving Comprehensive Cancer Center (HICCC), assistant professor of obstetrics and gynecology at Columbia University Irving Medical Center (CUIMC) and first author of the article.

“Antenatal carrier screening includes genetic testing, which is primarily done to identify mutations that affect the fetus or pregnancy, but it also provides an opportune time for testing mothers.”

Simulation study demonstrates cost-effectiveness of BRCA1 testing during obstetric care

The study simulated the clinical trajectory of a hypothetical cohort of 1,429,074 pregnant patients who would have received BRCA1 testing in the United States if it had been added to prenatal carrier screening. This number of patients was chosen based on previous studies showing that 39 percent of pregnant patients undergo enhanced carrier screening.

The model started with patients aged 33 years, based on the median age of carrier prenatal screening in the US, and followed them to age 80, tracking the primary outcome of cost-effectiveness of BRCA1 testing at carrier prenatal screening, as well as secondary outcomes such as positive results for BRCA1 mutation, cancer incidence, cancer deaths and direct medical costs.

The team found that adding the BRCA1 test led to the identification of an additional 3,716 BRCA1-positive patients, the prevention of 1,394 cases of breast and ovarian cancer, and 1,084 deaths. Compared with no BRCA1 testing, adding BRCA1 to antenatal carrier screening was cost-effective, with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life year.

“People often have a fatalistic view of cancer genetics and believe that simply recognizing their genetic risk or susceptibility to developing cancer is a sign that they will definitely get it and die from the disease,” said Dr. Melissa Frey, co-director of the Genetics Program and Personalized Cancer Prevention and Associate Professor of Obstetrics and Gynecology at Weill Cornell Medicine.

"It's critical to understand that using cancer genetics to understand a person's lifetime risk of developing cancer does not increase that person's risk—on the contrary, it gives health care professionals the tools they need to prevent cancer and save lives," said Dr. Frey, who also is the senior author of the paper and a gynecologic oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Expansion beyond BRCA1

Although they only examined BRCA1, the researchers believe that adding other hereditary cancer genes during prenatal screening of carriers—such as BRCA2, RAD51C, RAD51D, BRIP1, and PALB2—may also be cost-effective. Dr. Diun notes that typical panels provided to patients at Columbia University's gynecologic oncology clinics look for mutations in more than 70 genes.

"For genetics companies, there is minimal cost increase to add additional genes," said Dr. Diun, who is also a gynecologic oncologist at NewYork-Presbyterian/Columbia University Irving Medical Center. “I would expect there to be an even greater benefit if all these genes were integrated. We could identify people with other mutations and potentially prevent them from developing other types of cancer.”

Currently, no prenatal carrier screening panels on the market include BRCA1 or other hereditary breast and ovarian cancer genes. Doctors Diun and Frey are in talks with genetics companies about including these genes in their products for women who are pregnant or planning to become pregnant.

The researchers hope to then initiate a prospective clinical trial to demonstrate feasibility and gather opinions from both patients and physicians about the process.