Recent research has provided valuable insights into the long-term outcomes of patients with pathogenic BRCA1 and BRCA2 mutations who undergo breast-conserving therapy, according to a study presented at the 2024 Society of Surgical Oncology (SSO) Annual Meeting.1
The observational study found that the risks of ipsilateral (12.2%) and contralateral (21.3%) breast cancer events in BRCA-mutation carriers who underwent breast-conserving therapy between 1977 and 2021 were higher than published estimates for non–mutation carriers. However, most patients in the cohort did not experience another cancer event and remained free of bilateral mastectomy at 10 years. Authors of the study emphasized that these results may better inform shared decision-making discussions between clinicians and patients with BRCA mutations who are choosing breast-conserving therapy.
The aim of our study was to help inform patients who choose breast-conserving therapy about the long-term risks.— Kerollos Nashat Wanis, MD, PhD
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“Ultimately, for patients who choose breast-conserving surgery, it’s important to know what the risk is,” said Kerollos Nashat Wanis, MD, PhD, a breast surgical oncology fellow at MD Anderson Cancer Center, Houston. “The purpose of the study was not to take a paternalistic stance about whether the recurrence risk is too high or too low, but rather to provide patients with the information they need to make the best decision based on their personal values and preferences.”
Kerollos Nashat Wanis, MD, PhD
As Dr. Wanis reported, current guidelines from the American Society for Radiation Oncology and SSO support breast-conserving therapy as an option for BRCA-mutation carriers with newly diagnosed breast cancer. Based on the guidelines, germline BRCA data should not prevent eligible patients from receiving breast-conserving therapy.2 However, most patients (82.5%) opt for bilateral mastectomy because of concerns about recurrence and future cancer risk.3
“The lack of randomized trials comparing breast-conserving therapy with bilateral mastectomy has left a gap in understanding the comparative effectiveness of these two strategies in women with BRCA-associated breast cancer, and many women will choose breast-conserving therapy,” said Dr. Wanis. “The aim of our study was to help inform patients who choose breast-conserving therapy about the long-term risks.”
Study Details
Dr. Wanis and colleagues identified 172 women with pathogenic BRCA1/2 mutations who were treated with breast-conserving therapy at MD Anderson Cancer Center between 1977 and 2021 in a prospectively maintained database. The patients were part of an institutional study through clinical cancer genetics and consented to have their information collected and followed.
The researchers computed Kaplan-Meier estimates of overall survival and survival without bilateral mastectomy from a cancer event, as well as the risk of an ipsilateral breast cancer and contralateral cancer. Survival and cumulative incidence curves for BRCA1 and BRCA2 carriers were compared using log-rank tests. Cox proportional hazards models were used to describe associations between clinicopathologic factors and ipsilateral and contralateral breast cancer events.
More Informed Shared Decisions
As Dr. Wanis reported, data revealed different clinical and pathologic features for patients with BRCA1 vs BRCA2 mutations. Women with BRCA1 mutations (n = 92) were more likely to have a younger age at diagnosis, be premenopausal, be White, and have hormone receptor–negative tumors; they also were less likely to receive endocrine therapy compared with BRCA2-mutation carriers (n = 80).
With a median follow-up of 11.8 years, the 10-year overall survival rate was 88.5%, and the survival rate without bilateral mastectomy from a cancer event was 81.3%. The risks of an ipsilateral breast cancer event and contralateral cancer were 12.2% and 21.3%, respectively. According to Dr. Wanis, risks continued to increase after 10 years of follow-up.
KEY POINTS
- In this cohort study (n=172), women with BRCA-associated breast cancer who underwent breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events; however, most never experienced either event and remained free of bilateral mastectomy at 10 years.
- Although the risks of ipsilateral (12.2%) and contralateral (21.3%) breast cancer events were higher compared with the general population, these findings provide valuable information that can help inform patients with BRCA-associated breast cancer choosing breast conservation.
The researchers also identified factors associated with long-term outcomes. Receipt of bilateral salpingo-oophorectomy was associated with a lower hazard of ipsilateral breast cancer (hazard ratio [HR] = 0.29, P = .03), whereas BRCA2-mutation carriers had a lower hazard of contralateral cancer (HR = 0.51, P = .15).
“As the indications for genetic testing expand and targeted therapies emerge, understanding the long-term outcomes of breast-conserving therapy in BRCA-mutation carriers becomes increasingly important,” said Dr. Wanis. He noted that despite the increased risks of ipsilateral and contralateral breast cancer events, most patients in this cohort did not experience another cancer event and remained free of bilateral mastectomy at 10 years.
“Patients who choose breast-conserving therapy can always opt for bilateral mastectomies in the future,” Dr. Wanis added. “There may also be alternatives to immediate bilateral mastectomy, such as prophylactic radiation of the contralateral breast.”4
What Next?
Dr. Wanis and colleagues plan to study breast-conserving therapy outcomes in cohorts where all patients with newly diagnosed breast cancer are tested for BRCA mutations, as recommended by the American Society of Breast Surgeons. This will allow for more robust generalizability to the full population of women with BRCA-associated breast cancer, with the goal of guiding shared decision-making discussions.
Expert Point of View
Julie A. Margenthaler, MD, FACS
Julie A. Margenthaler, MD, FACS, Professor of Surgery at Washington University School of Medicine, St. Louis, said these data should lead to more informed discussions between clinicians and patients who are considering breast-conserving therapy.
“This provides evidence that breast-conserving therapy can be safely offered to women with BRCA1 and BRCA2 mutations,” Dr. Margenthaler told The ASCO Post. “Many women with these mutations who have a newly diagnosed breast cancer do opt for bilateral mastectomy. However, breast conservation remains an option, and surgeons should feel comfortable discussing this with patients who want to maintain their breasts and be followed closely for future primary tumors.”
DISCLOSURE: Dr. Wanis reported no conflicts of interest. Dr. Margenthaler reported no conflicts of interest.
REFERENCES
1. Wanis KN, Kuerer HM, Sun SX, et al: Clinical outcomes in BRCA mutation carriers treated with breast conserving therapy. 2024 Society of Surgical Oncology Annual Meeting. Abstract 12. Presented March 22, 2024.
2. Tung NM, Boughey JC, Pierce LJ, et al: Management of hereditary breast cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology guideline. J Clin Oncol 38:2080-2106, 2020.
3. Chiba A, Hoskin TL, Hallberg EJ, et al: Impact that timing of genetic mutation diagnosis has on surgical decision making and outcome for BRCA1/BRCA2 mutation carriers with breast cancer. Ann Surg Oncol 23:3232-3238, 2016.
4. Evron E, Ben-David AM, Goldberg H, et al: Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer. Ann Oncol 30:412-417, 2019.
