Undergoing prophylactic salpingo-oophorectomy (PSO) after previous surgery for BRCA1/BRCA2 breast cancer was associated with a significantly reduced risk of death, according to an Italian retrospective cohort study.
Of 480 patients treated between 1972 and 2019 at a single center who were found to carry a BRCA1 or BRCA2 gene variant, PSO was associated with a significantly lower risk of death (HR 0.40, 95% CI 0.25-0.64, P<0.001), reported Gabriele Martelli, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, and co-authors.
This was especially evident for patients carrying the BRCA1 variant (HR 0.35, 95% CI 0.20-0.63, P=0.001), those with triple-negative disease (HR 0.21, 95% CI 0.09-0.46, P=0.002), and those with invasive ductal carcinoma (HR 0.51, 95% CI 0.31-0.84, P=0.008), they noted in JAMA Surgery.
“We conclude that for patients carrying a BRCA1 or BRCA2 variant undergoing breast cancer surgery, PSO should be performed as early as possible, particularly for those with the BRCA1 variant, to reduce overall mortality,” Martelli and team wrote.
About 8% of breast cancer cases are linked to inherited BRCA1/2 genetic variants, which are responsible for a higher risk of breast and ovarian cancers. BRCA1 cancer is more often high-grade and triple-negative, and patients with BRCA1/2 breast cancer have a higher risk of contralateral breast cancer and ipsilateral breast tumor recurrence (IBTR).
PSO was not associated with risk of contralateral breast cancer or IBTR. While initial or delayed prophylactic mastectomy was associated with a reduced risk of IBTR, this was not the case for breast cancer-specific mortality.
Though treatment options include breast-conserving surgery such as quadrantectomy, prophylactic mastectomy, or PSO, few studies have compared the outcomes of such treatments for patients with BRCA1/2 breast cancer. The studies that have investigated these outcomes found that PSO for BRCA1/2 breast cancer was associated with a drop in mortality risk from ovarian, fallopian tube, or peritoneal cancer; a reduction in all-cause mortality; and a reduced risk for breast cancer-specific mortality.
Steven Narod, MD, of the Women’s College Hospital in Toronto and the University of Toronto, who has worked on a number of these studies, but was not involved in the current study, told MedPage Today, “I do agree with the conclusion that everyone with a BRCA1/BRCA2 mutation should have an oophorectomy, not just to prevent ovarian cancer but to prevent death from breast cancer.”
However, he also pointed to some flaws in the study design, including the fact that patients underwent surgery starting in 1972, but genetic testing did not become clinically available until 1996. It is unclear from the study when genetic testing was done.
“As far as I can tell, who[ever] had genetic testing was alive at the time of genetic testing, which would result in better survival than we would expect,” Narod said.
He also noted that olaparib (Lynparza) “gives you a reduction [in risk of death] of about 10% or 15%, whereas the oophorectomy gave a reduction of 80%, which is profound.”
In future studies, he continued, “I think it’s important to look within people that had both olaparib and oophorectomy [to see] if the oophorectomy is sufficient over chemotherapy,” and how they might work together.
Tehillah Menes, MD, of Sheba Medical Center in Ramat Gan, Israel, who was also not involved in the study, told MedPage Today in an email that the patients undergoing the PSO intervention might have done so because they were healthier, with fewer comorbidities and a better overall prognosis. That a “lower proportion of women who underwent PSO died from breast cancer can at least partially be explained by this nonrandom ascertainment of women to PSO.”
Additionally, though she said that, “we will continue to recommend PSO to most of these women,” she added, “I am not convinced that the data here support a generalized recommendation for all BRCA1 carriers to undergo PSO at the time of breast cancer surgery.”
A more individualized approach that considers “the women’s specific characteristics including age, comorbidities, breast cancer features, and response to preoperative systemic treatment (if was given) seems more appropriate at this time,” she noted.
For this study, Martelli and colleagues followed 480 consecutive patients at the Italian National Cancer Institute in Milan who underwent surgery for invasive breast cancer. BRCA1/2 testing was given to patients with a family history of breast or ovarian cancer or diagnosis at a young age. Patients with synchronous bilateral breast cancer, distant metastases at diagnosis, previous cancer at another site (except nonmelanoma skin cancer), or previous PSO were excluded.
Patients underwent either quadrantectomy or mastectomy as the primary surgery, and all patients were advised to undergo both PSO and prophylactic mastectomy, though not all did (62.5% underwent PSO and 34% underwent prophylactic mastectomy). Median age at initial surgery was 40 years; 60.4% had a BRCA1 variant, and 39.6% had a BRCA2 variant. Median follow-up was 16.5 years, with no patients lost to follow-up.
The researchers determined disease status or cause of death from clinical records or by contacting patients’ general practitioners.
Martelli and team noted that patients were not randomized to treatment in this study, which was a limitation. In addition, “although PSOs were performed to prevent ovarian cancer (not as a treatment for breast cancer), avoiding possible bias due to differences in breast cancer characteristics influencing whether PSO was performed, an unknown number of patients with a BRCA variant who refused variant testing could not be included in the study, which may have introduced bias.”
Martelli reported no conflicts of interest. Study co-authors reported relationships with AstraZeneca, Eli Lilly, Daiichi Sankyo, Pfizer, Roche, Foundation One, Illumina, and Novartis.
Narod reported no conflicts of interest.
Source Reference: Martelli G, et al “Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection” JAMA Surg 2023; DOI: 10.1001/jamasurg.2023.4770.