Salpingo-oophorectomy and risk of ovarian cancer in women with a BRCA1 or BRCA2 mutation
Commentary by Dr Graeme Suthers
The article:
Finch A, Beiner M, Lubinski J et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006;296:185–92
The reviewer:
Dr Graeme Suthers is the Head of the Familial Cancer Unit at the Women's and Children's Hospital in Adelaide.
Summary
Abbreviations
Confidence Interval (CI), Hazard Ratio (HR)
Study Design
This prospective cohort study included 1828 women with known BRCA1 or BRCA2 mutations who were recruited between 1992 and 2003 from 32 centres in Canada, United States, Europe and Israel. The study compared women who had undergone bilateral prophylactic oophorectomy to women who had not undergone this procedure. The primary outcome was the incidence of ovarian, peritoneal, and fallopian tube cancer. The mean follow-up was 3.5 years.
Findings
Thirty percent of the women (n=555) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 27% (n=490) underwent the procedure after entering the study, 43% (n=783) did not undergo the procedure.
In the women with intact ovaries, 32 cancers were detected. For those who underwent oophorectomy after entering the study, 11 cancers were identified at the time of the procedure. Seven cancers were detected in women who had already undertaken prophylactic oophorectomy.
After adjustment for covariates, oophorectomy was associated with a decreased risk of cancer (HR: 0.20; 95% CI: 0.07, 0.58; p=0.003).
Conclusion
The authors found that oophorectomy reduced the risk of ovarian and fallopian tube cancer in women with BRCA1 or BRCA2 mutations.
Commentary
What does this article add to existing clinical evidence in this area?
This study represents the largest prospective study of the efficacy of prophylactic oophorectomy in the management of gynaecological cancer risk in carriers of BRCA1 and BRCA2 mutations. Previous studies have estimated that prophylactic oophorectomy can reduce the relative risk of ovarian cancer by up to 95%. However, these studies have principally used historical or cross-sectional designs and are thereby subject to bias. Prophylactic oophorectomy, particularly in a pre-menopausal woman, represents a significant intervention and it is essential that the benefits and hazards of this procedure be clearly defined.
How adequate was the methodology used in addressing the aims of this study?
This was a multi-centre prospective study, with a total of 1800 participants. However, the women were observed for very different periods of time. The mean follow-up period for all participants was only three and a half years, with the range being from a few days to 10 years. Hence, although the study was indeed prospective, the data were derived from a lot of short-term observations.
What are the implications of this study for clinical practice in Australia?
This study confirms that prophylactic oophorectomy is very effective at reducing the risk of subsequent ovarian cancer. The risk was reduced by 80% (ie Hazard ratio of 0.20; 95% CI: 0.07, 0.58) with a confidence interval that almost reached the 95% risk reduction observed in the previous historical and cross-sectional studies.
During the course of the study, 490 women underwent prophylactic oophorectomy. Of these, 11 (2%) were found to have occult cancer at the time of this surgery. Three of these 11 cancers were primary fallopian tube carcinomas. It is often difficult to differentiate between primary tubal versus ovarian cancers in women with established disease, but this distinction was feasible in these patients identified with occult cancers. This observation highlights the importance of removing the fallopian tubes together with the ovaries. At this stage, it is not known what residual risk of tubal cancer remains if the uterus (with the fundal portion of the tubes) is retained.
Of the 1045 women in total who had prophylactic oophorectomies, seven subsequently developed primary peritoneal carcinoma. The cumulative risk of primary peritoneal over 20 years was 4%. It was striking that six of these women were diagnosed within five years of their prophylactic surgery; one woman was diagnosed 20 years after her surgery. This raises the possibility that these six women had occult ovarian cancer with local seeding that had been missed at the time of the prophylactic surgery. If this interpretation is correct, then the incidence of occult cancer at the time of prophylactic surgery is higher than reported, and the long-term risk of primary peritoneal carcinoma after prophylactic surgery is much lower. It is clearly essential that the ovaries and fallopian tubes be examined in detail following prophylactic surgery. At this stage, it is not known whether examination of peritoneal washings at the time of surgery would identify occult cancers that might otherwise be missed.
Acknowledgement
The National Breast Cancer Centre (NBCC) acknowledges the contribution of Clinical Associate Professor Peter Grant, member of the NBCC’s Clinical Expert Advisory Panel, in reviewing this first issue of Clinical Update – Ovarian Cancer.
