Summary
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Original Article
The Rate of Oophorectomy Among Women With Genetic Alterations
Oncology Times
By Catlin Nalley
New data found that 10-15 percent of women with pathogenic variants (PV)/variants of uncertain significance (VUS) in genes not associated with a high risk of ovarian cancer reported undergoing an oophorectomy without a clear indication. This study, which was presented at the ASCO 2020 Annual Meeting, raises concerns regarding the potential for unnecessary procedures (Abstract 1508).
“Most genetic testing for cancer susceptibility is now done using multigene panels, and the identification of pathogenic variants associated with the risk of ovarian cancer greater than 5 percent, such as in BRCA1, BRCA2, BRIP1, RAD51C, and RAD51D, allow for the identification of women who may benefit from risk-reducing salpingo-oophorectomy (RRSO) as recommended by guidelines,” noted study author Susan M. Domchek, MD, from Penn Medicine.
“However, VUS should not be used to alter medical management recommendations,” she continued. “And, for PVs in other genes not associated with the risk of ovarian cancer greater than 5 percent, there are no current guidelines for recommending oophorectomy. There is potential for harm for oophorectomy, particularly in premenopausal women.”
Study Methods
The Prospective Registry of Multiplex Testing (PROMPT) is an online registry of individuals with a genetic alteration detected on multiplex panel testing for cancer susceptibility. Participants self-enroll, completing baseline and annual follow-up questionnaires. From September 2014 to April 2020, PROMPT enrolled 7,688 participants (93.9% female).
The aims of the current analysis, according to Domchek include the following: examine the uptake of RRSO in those with genetic alterations without a risk of ovarian cancer greater than 5 percent; describe the use of RRSO among individuals with different genetic test results and how this use varies across personal and family history; and describe provider recommendations in those with RRSO.
Of the 7,688 enrolled patients, the researchers excluded men and those who did not fill out the section on surgical history. Of the 1,691 individuals who described undergoing oophorectomy, 248 were excluded because they had a pathogenic or likely pathogenic variant in a high risk-ovarian cancer susceptibility gene, according to Domchek.
“An additional 474 patients whose oophorectomy was for the treatment of benign disease were excluded, as well as another 494 who specified that their oophorectomy was for cancer treatment,” she outlined.
Of the remaining 457 patients, 114 had VUS in genes associated with a high risk of ovarian cancer, 220 had a personal history of breast cancer and no ovarian cancer VUS, and 123 had no personal history of disease and no ovarian cancer VUS.
Key Findings
Evaluating the uptake of RRSO across PROMPT, the researchers found that, among patients with VUS in ovarian cancer genes, 15.6 percent reported having an oophorectomy. In patients with a personal history of breast cancer, 10.9 percent reported having the procedure compared to 6.7 percent in those with no personal history of disease.
“We then looked at the oophorectomy by family history of ovarian cancer overall,” noted Domchek. “Over 70 percent of individuals who had no family history of first- or second-degree relatives with ovarian cancer reported preventative oophorectomy. The vast majority (71.8%) were performed under the age of 50. Breast cancer patients were more likely to have no family history of ovarian cancer and undergo oophorectomy at an early age.”
When examining provider recommendations, researchers found no difference in the three groups when looking at whether a provider recommended the preventative surgery. “However, the individuals with VUS in ovarian cancer susceptibility genes were more likely to report that their provider recommended or discussed this as an option,” Domchek explained during her presentation.
“Overall, 66 percent stated that their provider recommended or discussed oophorectomy as an option,” she continued. “This provider recommendation did not seem to differ based on whether or not there was a family history of ovarian cancer and did not differ depending on the timing of oophorectomy.”
When examining provider recommendations by genetic alteration, researchers found that overall patients reported that their providers often either recommended or discussed preventative removal of the ovaries as an option. It was more likely in PALB2 pathogenic or likely pathogenic mutation carriers that providers either recommended (68%) or recommended and discussed as an option (89.2%), according to Domchek.
Potential Limitations, Implications
There were limitations to the study, Domchek acknowledged, including self-referral with corresponding ascertainment bias. Additionally, medical history and provider recommendations are self-reported. While genetic testing information was confirmed by test report or ClinVar, she noted that some reports had insufficient information to classify.
“And, although reported as preventative oophorectomy, treatment considerations may certainly be confounders in our breast cancer patients,” Domchek said. “There is also uncertainty regarding the optimal threshold for oophorectomy. [For instance,] where should PALB2 be classified? Although, one can make an argument that early oophorectomy in this situation may not necessarily be warranted.”
Despite study limitations, Domchek concluded that these data raise the concern that some women are undergoing preventative oophorectomy, often under age 50, without clear indications.
“If validated that 10-15 percent of those with ovarian cancer VUS, CHECK2, and ATM pathogenic/likely pathogenic variants are undergoing oophorectomy, often while pre-menopausal, there is the potential for harm,” she noted.
“Although ovarian suppression is increasingly used for treatment of breast cancer, further work is needed to determine if genetic information is leading to decisions regarding permanent oophorectomy versus reversible injections,” Domchek stated. “And, further data are also needed on communication between patients and providers regarding the implications of genetic information and management options.”
Catlin Nalley is a contributing writer.