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Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices
  1. Catherine H. Watson1,
  2. Lindsay Soo2,
  3. Brittany A. Davidson2,
  4. Laura J. Havrilesky2,
  5. Paula S. Lee2,
  6. Leah J. McNally2,
  7. Rebecca A. Previs2,
  8. Angeles Alvarez Secord2,
  9. Andrew Berchuck2 and
  10. Noah D. Kauff3
  1. 1 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA
  2. 2 Duke Cancer Institute, Durham, North Carolina, USA
  3. 3 Northwell Health Cancer Institute, Lake Success, New York, USA
  1. Correspondence to Dr Catherine H. Watson, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA; catherine.h.watson{at}duke.edu

Abstract

Objective Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology.

Methods Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (relative risk (RR)=30–60), RAD51C (RR=5.0), or ATM (RR=1.5–2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ2 testing for statistical analyses, comparing results according to mutation type and demographic information.

Results A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. Response distribution for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes (p<0.001).

Conclusions Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.

  • ovarian cancer
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Footnotes

  • Contributors CHW: conceptualization, design, implementation, statistical analysis, and writing of first draft. LS: conceptualization, design, implementation, and review. BD, LH, PSL, RP, LM, AAS, AB: conceptualization, design, editing, and review, NDK: conceptualization, design, implementation, review of statistical analysis, editing, and review.

  • Funding This study was partially supported by the Gray Foundation and Project Hope for Ovarian Cancer Research and Education.

  • Competing interests LH discloses that she has research grants from Tesaro and AZ. AAS discloses that she has received clinical trial grant funding from AbbVie, Amgen, Astellas Pharma Inc, AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Clovis, Eisa, Exelixis, Immutep Ltd, Incyte, Merck, PharmaMar, Roche/Genentech, Seattle Genetics Inc, Tesaro/GSK, and VBL Therapeutics. She has also received honoraria for advisory boards from Aravive, AstraZeneca, Clovis, Cordgenics, Eisai, Janssen/Johnson&Johnson, Merck, Mersana, Oncoquest, Roche/Genentech, and Tesaro. RP discloses that she has received grant funding from Myriad. NDK discloses that he is a consultant for Merck and AstraZeneca, and receives honoraria from BGI.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the institutional review board of Duke University (Duke IRB Pro0010493).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as supplementary information.

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