Management of high, moderate, and low penetrance ovarian cancer susceptibility gene mutations: An assessment of current practice patterns.
Watson, CH; Davidson, BA; Havrilesky, LJ; Lee, PS; McNally, L; Moss, H; Previs, RA; Puechl, A; Secord, AA; Berchuck, A; Kauff, ND
Published in: Journal of Clinical Oncology
1536 Background: Limited information exists regarding appropriate risk-reduction strategies for women with moderate and low penetrance ovarian cancer (OVCA) susceptibility mutations. We sought to assess current practice patterns for women with these genetic changes through a survey of members of the Society of Gynecologic Oncology (SGO). Methods: All full SGO members were e-mailed a survey consisting of two vignettes: 1) a 35-year-old premenopausal woman who desires pregnancy; 2) a 55-year-old postmenopausal woman with multiple comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (RR = 30-60), RAD51C (RR = 5.0) or ATM (RR 1.5-2.0) OVCA susceptibility mutation. Respondents were queried about their preferred management approach. Chi-square test was used for statistical analysis. Results: 193 (15%) of 1284 SGO members responded. 58% were in academic practice. For the premenopausal woman, 52%, 13% and 6% would perform an RRSO prior to age 40 in the setting of a BRCA1, RAD51C and ATM mutation respectively. 47%, 68% and 9% would perform RRSO at 40-50; and 0%, 9% and 23% would perform RRSO at menopause, depending on the gene mutated. For the postmenopausal woman with comorbidities, 98%, 85% and 42% would proceed with RRSO in the setting of a BRCA1, RAD51C and ATM mutation respectively; 2%, 8% and 39% would observe (with/without screening); and 0%, 7% and 19% would do further research prior to proceeding. Distribution of responses for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes [p < 0.001]. Conclusions: Respondents were more likely to perform RRSO earlier and more frequently in the setting of a BRCA1 mutation compared to either a RAD51C or ATM mutation. However, there was lack of consensus in management of the moderate and low penetrance OVCA susceptibility mutations. These patterns likely reflect the limited information available regarding the timing and magnitude of risk associated with these genes. Given the immediate and long-term morbidity of oophorectomy, more data regarding age-specific risks and appropriate risk-reduction strategies for moderate and low penetrance OVCA susceptibility mutations is needed.
