by Carmen Phillips
People with harmful changes (pathogenic variants) in the BRCA1 or BRCA2 genes have a significantly increased risk of breast and ovarian cancer.
Source: National Cancer Institute
For women with genetic testing that identifies “harmful changes” in genes BRCA1 either BRCA2 leading medical groups recommend that you take specific steps to reduce your chance of being diagnosed with, or dying from, breast and ovarian cancer.
The results of two recent large studies now add to the findings of previous studies indicating that following these recommendations reduces the risk of dying from these cancers.
In the first study, women with harmful changes in the gene BRCA1 Those who had regular screening with magnetic resonance imaging (MRI) of the breast, known as MRI surveillance, were less likely to die from breast cancer in subsequent years than those who did not. However, the same benefit was not seen in women with harmful changes in the gene. BRCA2.
In the second study, the effect of surgery known as bilateral salpingo-oophorectomy on reducing the risk was analyzed. Through this surgery, both ovaries and the fallopian tubes are removed. In this study it was found that those people with harmful changes in genes BRCA1 either BRCA2 Those who had this surgery had a lower risk of dying from ovarian cancer and breast cancer than those who did not.
The results of both studies were published on February 29 in the JAMA Oncology.
“These studies show that [estas] Cancer risk control strategies…can save lives,” wrote Drs. Meghna Trivedi and Katrina Armstrong of Columbia University Irving Medical Center in an editorial that accompanied both studies.
Notably, however, almost all participants in the studies were white, raising the question of what these results mean for women of other ethnic and racial backgrounds.
“We need to be careful how we interpret the results” for people in these groups, said Dr. Goli Samimi of the National Cancer Institute’s (NCI) Division of Cancer Prevention, who was not involved in the study.
“It is to be hoped that [estos hallazgos] encourage similar studies involving a diverse population of participants,” added Dr. Samimi.
Recommendations for genetic testing and MRI surveillance compared to reality
There are many inherited genes that increase the risk of cancer. Perhaps of most concern for breast and ovarian cancer are harmful changes (often called pathogenic variants) in genes BRCA1 and BRCA2.
For example, 60% to 70% of people with harmful changes in BRCA1 either BRCA2 will be diagnosed with breast cancer when they are 70, compared to only 13% of those without these changes.
Because of the significant risk associated with these inherited genetic changes, leading cancer organizations recommend that people who have them consider taking steps to reduce the likelihood of getting sick or dying from one of these cancers, explained Dr. Tuya Pal, of the Vanderbilt-Ingram Comprehensive Cancer Center in Tennessee, and a member of the study team.
But hereditary cancer experts emphasize that the recommendations are theoretical. Because its application in the real world is a completely different matter. The barriers and challenges are numerous, Drs Trivedi and Armstrong noted.
“First, more must be done to identify a larger number of” people who have harmful changes in BRCA1 and BRCA2through more genetic testing, they noted.
The study’s principal investigator, Dr. Steven Narod of Women’s College Hospital in Toronto, agreed. Recent studies show that people at risk are increasingly undergoing genetic testing. But still, “not enough people are getting tested,” Dr. Narod explained.
For those who can be tested, Dr. Pal emphasized that it is essential to first receive advice from a provider with experience in genetics and cancer risk. This type of counseling helps people understand the personal meaning of different test results, including possible risk reduction measures.
Who is at risk for harmful changes in BRCA?
According to the United States Preventive Services Commission (USPSTF), people at increased risk of having inherited harmful changes in BRCA1 and BRCA2 They are those “with a personal or family history of breast, ovarian, fallopian tube or peritoneum cancer, or with an ancestry related to” these changes.
In some cases, access to licensed genetic counselors is a problem, Dr. Samimi said. For example, in one study it was observed that these advisors are concentrated mainly in the most populated areas.
Getting MRI surveillance done is sometimes a challenge. There are barriers such as transportation problems and lack of access to centers where MRIs are offered. Additionally, despite recommendations from medical organizations, not all insurers cover MRI surveillance of women with harmful changes in BRCA1 and BRCA2.
Due to ongoing challenges in understanding recommendations around risk reduction and access to testing, Dr. Samimi explained that it is good that there is more data to support them and raise awareness about them.
That’s where the large international research program that Dr. Narod helped start in the mid-1990s, called the Hereditary Breast Cancer Clinical Study Group, comes into play. Known as a cohort study, it was initially planned for only a few hundred participants. It now has almost 20,000 participants with harmful changes in BRCA1 either BRCA2.
Decrease in deaths from breast cancer
The MRI surveillance study included about 2,500 women participating in this larger research program. About 1,750 were monitored by MRI during the study, and on average, they had five MRIs during follow-up.
The approximate average follow-up of the participants was 9 years; About 14% in both the MRI and non-MRI groups received a breast cancer diagnosis during the study.
Only a small number of participants died from breast cancer during the study. However, among people with harmful changes in BRCA1MRI surveillance was estimated to decrease breast cancer deaths over the next 20 years by about 3%.
The decreased likelihood of death from breast cancer in women with harmful changes in BRCA1 It was also observed when the comparison was limited to women in the unsurveillance group who received at least one mammogram during the study period.
The absence of a statistical decrease in breast cancer deaths among women with changes in BRCA2 This may be largely due to two factors, Dr. Narod explained: the small number of participants with these changes who had died from breast cancer.
Surgery reduces the probability of dying from breast and ovarian cancer
The other study included nearly 4,300 women, about two-thirds of whom had had surgery. All participants had at least one bilateral oophorectomy (removal of both ovaries) and most had a salpingo-oophorectomy (removal of both ovaries and fallopian tubes).
About 20% of all participants were diagnosed with cancer during the study period (median follow-up of 9 years), most with breast and ovarian cancer, and most deaths were due to cancer.
The percentage of breast cancer diagnoses was very similar between those who did and did not have preventive surgery; However, the percentage of ovarian cancer diagnoses was much higher in those who did not have surgery.
Overall, participants who had an oophorectomy were less likely to die from any cause, which was the primary measure of the study.
In particular, for ovarian cancer, about 3.5 percent of those who did not have surgery died from ovarian cancer during the study period, compared to about 0.25 percent of those who had surgery. For breast cancer, it was 2% and 1%.
More genetic testing to maximize risk-reducing treatment
Both studies, Dr. Pal said, provide strong evidence for the potential benefits of surveillance with MRI or salpingo-oophorectomy. “This data has a great impact,” she explained.
Dr. Samimi said she is hopeful that these new findings will further educate women at risk of having inherited harmful genetic changes to get tested and also have the information needed for doctors and their patients to talk about options to reduce that risk.
We hope that these conversations will also be extended to the close blood relatives of those who present these changes, he noted.
“We need to do better to communicate with families about their risk,” he continued.
The NCI funds one of these initiatives. The Traceback program focuses on helping researchers identify women who had ovarian cancer but were never tested for cancer-related genetic changes. Once they are identified, they and their family members will be offered the opportunity to be tested.
Dr. Naron pointed out that in Canada there is a study called the Screen Project that provides evidence of harmful changes in BRCA1 and BRCA2 to Canadian citizens aged 18 or over.
Drs Armstrong and Trivedi emphasized that work remains to be done across the board to “maximize” the care needed to prevent more deaths from breast and ovarian cancer. To achieve that goal, they continued, “it will be necessary to provide equitable access and coverage [de seguro]” for all recommended risk reduction actions.