Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis
Introduction
Mutations in DNA repair pathways, including breast-cancer susceptibility gene 1 (BRCA1) and breast-cancer susceptibility gene 2 (BRCA2) mutation carries, predispose women to an elevated lifetime risk for ovarian cancer (OC) and breast cancer (BC) (National Comprehensive Cancer Network Guidelines, 2018). While the role of bilateral risk-reducing mastectomy is still controversial, risk-reducing salpingo-oophorectomy (RRSO) represents nowadays the main effective prophylactic OC risk measure that should be proposed to BRCA carries, especially once childbearing is complete (National Comprehensive Cancer Network Guidelines, 2018; Paluch-Shimon et al., 2016; De Felice et al., 2015). In fact, in this setting of patients, prophylactic RRSO is associated with an OC risk-reduction of approximately 80% (hazard ratio, HR 0.19, 95% confidence interval, CI = 0.13 – 0.27) and it seems also to reduce BC risk by approximately 50% (HR 0.53, 95% CI = 0.33 – 0.84) (Rebbeck et al., 1999; Marchetti et al., 2014a). Subsequent hormone replacement therapy (HRT), including estrogen and progesterone alone or in combined therapy, remains a major concern, especially concerning its potential influence on BC risk. In clinical practice, HRT choice after RSSO is mainly driven by physician and patient preference to manage acute symptoms of surgically-induced menopause (De Felice et al., 2017).
This meta-analysis aims to stress the real impact of HRT after RSSO on BC risk in order to define the better standard of care for the management of BRCA1 and BRCA2 mutation carriers after prophylactic RSSO.
Section snippets
Search strategy and selection criteria
The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was followed to perform this meta-analysis. It includes both prospective cohort trials and retrospective studies, written in English, without any restrictions on publication date. To be eligible, published and unpublished trials had to estimate BC incidence in BRCA1 and BRCA2 mutation carriers who underwent RRSO and received or not received HRT after prophylactic surgery. Systematic literature electronic
Results
A total of 3 studies were identified (Kotsopoulos et al., 2018; Rebbeck et al., 2005; Gabriel et al., 2009). The vast majority of articles were excluded due to different topic and format, such as review and case report/series. Of the 6 potentially eligible studies, 3 were excluded because of the absence of BC incidence data (n = 2) or overlapping data (n = 1). Overall, 3 studies representing 1100 patients were included in the meta-analysis. Details by study are presented in Table 1.
BC risk
Discussion
We demonstrated that HRT seems to be a safe therapeutic option in BRCA 1 and 2 mutation carriers undergoing RRSO, regardless of the study design (HR = 0.98; 95% CI 0.63–1.52). Data were also confirmed in the subgroup analysis including only prospective/observational studies. Further, it seems that those who receive E-alone have a lower, not significant trend for BC risk compared with those who receive estrogen plus progesterone (OR = 0.53; 95% CI 0.25–1.15).
A woman identified as a BRCA mutation
Conclusion
This meta-analysis suggests that there is no clear indication of choice on BC risk in prescribe or not prescribe HRT after prophylactic RRSO. Surely, further clinical investigation is needed.
Conflict of interest statement
The authors declare that they have no competing interests.
Funding sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Authors’ contributions
Conception and design: XXX.
Collection and assembly of data: XXX.
Data analysis and interpretation: XXX.
Manuscript writing: XXX.
Final approval of manuscript: All authors.
Acknowledgement
None.
Francesca De Felice was born in Rome in 1983. She graduated from the Faculty of Medicine of the University of Rome “Sapienza” in 2007. She obtained the license to practice medicine in Italy in 2008. She was specialized in Radiation Oncology at the University of Rome “Sapienza” in 2012. In 2013 she was a medical attendant at the Département de Radiothérapie, Institut de Cancérologie Gustave Roussy, Villejuif-Parigi and in 2014 she was a medical attendant at the Division of Clinical Oncology,
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Francesca De Felice was born in Rome in 1983. She graduated from the Faculty of Medicine of the University of Rome “Sapienza” in 2007. She obtained the license to practice medicine in Italy in 2008. She was specialized in Radiation Oncology at the University of Rome “Sapienza” in 2012. In 2013 she was a medical attendant at the Département de Radiothérapie, Institut de Cancérologie Gustave Roussy, Villejuif-Parigi and in 2014 she was a medical attendant at the Division of Clinical Oncology, Guy’s and st. Thomas’ Hospital, King’s College, London, UK. From 2012 onwards she is a PhD student at the Department of Radiological Sciences, Oncology, and Pathology, University of Rome "Sapienza". She is author of several indexed papers, all in the field of clinical and experimental oncology.
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Equal contribution.