- BRCA carriers had similar overall and breast cancer-specific survival with risk-reducing mastectomy or surveillance.
- Risk-reducing mastectomy reduced breast cancer incidence by 94% compared with surveillance.
- The data are consistent with those of previous studies going back more than a decade.
Carriers of BRCA pathogenic variants had similar breast cancer-specific survival (BCSS) and overall survival (OS) whether they chose risk-reducing surgery or radiographic surveillance, a large British cohort study showed.
After a median follow-up of 6-8 years in 1,200 women, four patients in the surveillance group had died of breast cancer as compared with two in the mastectomy group. OS was similar across 10-year age groups except women ages 50-59, wherein the surveillance group had more deaths unrelated to BRCA pathogenic variants (pvBRCA).
Survival did not differ between the groups even though prophylactic mastectomy significantly reduced the risk of breast cancer, reported Ashu Gandhi, MD, of the University of Manchester, and colleagues in the Journal of Clinical Oncology.
"For women choosing surveillance over risk-reducing surgery, our data may reassure that OS is not compromised," the authors concluded. "Although BRRM [bilateral risk-reducing mastectomy] reduced breast cancer incidence, potentially sparing women the requirement for radiotherapy and or chemotherapy, particularly in pvBRCA1-related cancers, imaging surveillance, as guided by national recommendations provides equivalent survival without our follow-up period."
"Longer follow-up is needed to see if any moderate survival differences emerge between imaging and BRRM," they added.
In addition to providing reassurance for women who choose surveillance, the study reinforces the concept that the decision to pursue BRRM is not solely a life-or-death question, said Katharine Schulz-Costello, DO, a surgical oncologist at City of Hope in Duarte, California.
While surgery lowers breast cancer incidence, BCSS and OS appear similar between woman choosing surgery and those undergoing structured imaging surveillance.
"These results highlight a critical conversation, in how we counsel high-risk patients," Schulz-Costello, who was not involved in the study, told MedPage Today. "Risk-reducing surgery remains a safe and effective strategy for cancer prevention and, thus, for avoiding cancer-directed therapy. At the same time, modern surveillance programs can detect early-stage disease that is highly treatable and unlikely to impact long-term survival."
"Importantly this underscores that there is no universal right choice," she added. "Decisions regarding risk-reducing surgery are personal and must incorporate age, individual risk tolerance, quality-of-life considerations, and body image. Our responsibility as physicians is not to direct patients toward a single pathology but to provide clear education, contextualize risk, and partner with each patient to determine the option that aligns best with her values."
The ability to quantify the risk associated with pathogenic variants has changed substantially in recent years with advances in molecular biology and genetics that have identified variants other than BRCA1/2, said Rachel Greenup, MD, a surgical oncologist at Yale School of Medicine in New Haven, Connecticut.
"The risk depends on the mutation women have and the biology of their first cancer," Greenup, who was not involved in the research, told MedPage Today. "So, the risk of an ATM mutation carrier getting a contralateral new primary breast cancer is significantly lower than the risk for a BRCA mutation carrier or a CHEK2 mutation carrier."
A recent "practice changing" study involving 15,000 women quantified the risk associated with five of the most common pathogenic variants. Investigators examined risk by race/ethnicity, menopausal status, and receptor status. Women who had an estrogen receptor-positive breast cancer had a lower risk of developing contralateral breast cancer as compared with those who had an estrogen receptor-negative cancer.
"It's more nuanced than we originally thought," said Greenup. "Once you're affected by cancer, the risk of a contralateral cancer depends on your mutation type, your menopausal status, and your tumor biology."
The findings from the current study are consistent with research published more than a decade ago, showing women with BRCA-associated breast cancer had similar OS whether treated with breast-conserving surgery or mastectomy, she added.
Gandhi and colleagues reported findings from an analysis of 1,205 women with pvBRCA1/2 but no personal history of breast cancer. Subsequently, 460 patients had BRRM and 745 chose surveillance. Consistent with previous studies, the annual incidence of breast cancer decreased significantly from 2.4% in the surveillance group to 0.15% in the BRRM group, a 94% reduction (P<0.001).
Annualized mortality was higher in the surveillance group (0.7% vs 0.25%), which the authors attributed to the surveillance group's older age at the time of testing for pvBRCA (ages 38.5 vs 37.2). However, OS and BCSS did not differ significantly between the groups.
"We did not find evidence of difference in actuarial life expectancy in women undergoing BRRM or surveillance until above the age of 60 years, after which survival curves separated in favor of BRRM," the authors stated. "However, the small numbers of women [n=94] and events [n=14 deaths] in the group of women older than 60 years make it difficult to draw firm conclusions."
The authors acknowledged the small number of deaths and breast cancer-specific deaths as a limitation of the data, along with the inherent limitations of a nonrandomized study.
Disclosures
The study was supported by the National Institute for Health Research.
Gandhi disclosed a relationship with Gilead Sciences. Co-authors disclosed relationships with Lilly, AstraZeneca, Pfizer, Novartis, AbbVie, and Everything Genetic.
Schulz-Costello and Greenup disclosed no relationships with industry.
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