By Lynda Williams, medwireNews Reporter
medwireNews: Risk-reducing (RR) surgery leads to improved overall survival (OS) for breast cancer patients carrying a BRCA1 or BRCA2 mutation, confirm two studies published in The Lancet Oncology.
The first study by Matteo Lambertini (IRCCS Ospedale Policlinico San Martino, Genova, Italy) and colleagues reports on the outcome of women diagnosed with stage I–III invasive breast cancer before the age of 40 years who chose to undergo RR mastectomy (RRM) or salpingo-oophorectomy (RRSO).
The BRCA BCY Collaboration cohort study included 5290 women from 109 centres across five continents, comparing 2910 patients who underwent RRM with 2380 who did not, and 2782 patients who underwent RRSO with 2508 who did not.
The majority (63.5%) of participants carried pathogenic alterations to BRCA1 and 66.8% had grade 3 breast cancer. Over half (52.8%) had hormone receptor-negative and 45.8% hormone receptor-positive disease, and 88.4% were HER-negative, meaning 49.1% of patients had triple-negative breast cancer.
After a median 8.2 years of follow-up, 13.0% of patients had died and 36.4% had experienced locoregional or distance recurrence, a second primary breast cancer or other malignancy, or death from any cause.
Women who underwent RRM had significantly better OS than those who did not, with a hazard ratio (HR) for death of 0.65, after adjusting for BRCA gene, age, tumour subtype and size, nodal status and other demographic, diagnostic and treatment factors. The corresponding 20-year restricted mean OS durations were 17.89 and 16.65 years.
Similarly, women who chose to undergo RRSO had significantly better OS than those who did not, with an adjusted HR of 0.58, and 20-year restricted mean OS durations of 17.73 and 16.67 years, respectively.
“This study underscores the importance of BRCA testing and personalised counselling regarding risk-reducing surgeries for BRCA carriers with young-onset breast cancer”, Lambertini et al write.
“Based on this evidence, RRM and RRSO were associated with a significant improvement in survival outcomes, justifying their consideration in tailored cancer risk management strategies for this special population”, they say.
“Future research should focus on long-term follow-up and patient-centred outcomes, including quality of life and reproductive considerations, to optimise shared decision making processes.”
The authors of the second study collated medical and genetic records for 3423 UK women who were diagnosed with breast cancer between 1995 and 2019. The patients were all aged 20–75 years and had a confirmed BRCA1 (n=1674) or BRCA2 (n=1740) alteration; nine patients had both.
Overall, 1855 patients underwent bilateral (B)SO at a median age of 48 years including a comparable 50.8% of BRAC1 and 57.5% of BRCA2 carriers. The remaining 1568 patients did not have the surgery.
Of note, the majority (88.7%) of study participants were White; Black and Asian women were significantly less likely to undergo BSO than their White counterparts (odds ratio=0.48 and 0.47, respectively).
In addition, BSO was significantly more common in women living in the least socioeconomically deprived areas of the UK than in those living in the most deprived areas (OR=1.38), observe Hend Hassan (University of Cambridge, UK) and fellow researchers.
And the rate of BSO was significantly higher in patients with oestrogen-positive than oestrogen-negative breast cancer (OR=1.83) and in those who received chemotherapy in their first year versus no chemotherapy (OR=2.28), but the surgery was significantly less common in women who received hormone therapy in their first year versus no hormone therapy (OR=0.71).
Over a median 5.5 years of follow-up, women who underwent BSO had a significantly lower risk of all-cause mortality and breast cancer-specific mortality than those who did not, with hazard ratios (HRs) of 0.52 and 0.55, respectively.
BSO was also linked to a significantly reduced risk of being diagnosed with a second non-breast cancer (HR=0.59). Moreover, receipt of BSO did not significantly affect the risk of having cardiovascular disease, ischaemic heart disease, cerebrovascular disease, contralateral breast cancer, or depression, or dying from non-breast cancer-specific causes.
“The evidence supports offering BSO to BRCA1 and BRCA2 pathogenic variant carriers with a personal history of breast cancer, as they appear to benefit from having the procedure, without evidence of an increased risk of adverse long-term health outcomes”, Hassan et al therefore conclude.
Writing in a linked comment, Virgilio Sacchini (Memorial Sloan Kettering Cancer Center, New York, USA) says that questions remain about the use of RR surgery, such as whether it is beneficial only to younger patients, and if the harm from the RR procedures outweighs the requirement for intense surveillance after conservative procedures.
“Two important points to consider for prophylactic oophorectomy among BRCA patients with breast cancer, especially for those with younger onset breast cancer, are how the desire for childbearing would require postponing risk-reducing oophorectomy, and how the possible use of hormonal replacement therapy after oophorectomy with hormonal therapy might not affect prognosis”, he acknowledges.
The commentator therefore concludes that “more data, and studies with longer follow-up, on the best timing for oophorectomy in young patients, the safety of hormonal replacement therapy in patients with previous breast cancer (and triple-negative breast cancer) and quality of life are needed.”
Keywords: BRCA, breast cancer, mastectomy, salpingo-oophorectomy
Lancet Oncol 2025; doi: 10.1016/S1470-2045(25)00152-4