In a long-term follow-up of an Israeli phase II trial reported in a research letter in JAMA Oncology, Evron et al compared prophylactic radiation therapy (RT) of the contralateral breast vs surveillance in BRCA pathogenic variant carriers with early-stage breast cancer.
Study Details
In the study, 162 BRCA1/2 pathogenic variant carriers (mean age = 49.7 years, range = 32–76 years) undergoing RT for unilateral breast cancer were enrolled between May 2007 and October 2017. Concurrent with RT to the ipsilateral breast, patients were permitted to choose prophylactic RT to the contralateral breast (n = 80) or surveillance (n = 82). The primary outcome measure of the current analysis was rate of contralateral breast cancer at 10 years.
Key Findings
During follow-up, one patient in the prophylactic RT group (1.3%) and nine in the surveillance group (10.9%; P = .02) underwent elective mastectomy and contralateral risk-reducing mastectomy. These patients were censored from the primary analysis at the time of risk-reducing mastectomy.
At a median follow-up of 10.4 years (range = 1.5–15.7 years), contralateral breast cancer had developed in 11 patients (13.8%) in the prophylactic RT group and 15 patients (18.3%) in the control group (P = .24). The median time to contralateral breast cancer was 90 months (range = 56–145 months) in the prophylactic RT group and 40 months (range = 3–127 months) in the surveillance group (P < .001). Overall, the incidence of contralateral breast cancer was low through 72 months and showed a sharp increase thereafter. Ipsilateral breast tumor recurrence occurred in six patients in each group (7.5% and 7.3%, P > .99). Median time to recurrence in all patients with ipsilateral breast tumor recurrence was 81 months (range = 32–171 months), with a 41-month delay to ipsilateral breast tumor recurrence among patients receiving prophylactic RT vs surveillance.
No significant differences were observed between groups in other breast cancer outcomes or other cancer events.
The investigators stated, “In this study, at 10.4 years, the rate of [contralateral breast cancer] in the treated group (13.8%) was lower than the reported rate of [contralateral breast cancer] in carriers of 25% to 30% in other studies… .Notably, the incidence of [contralateral breast cancer] remained low until 72 months, reflecting a significant delay in the occurrence of [contralateral breast cancer] in the treatment group… .This novel approach, albeit controversial, is supported by the findings that highlight the need for a larger international trial.”
Ella Evron, MD, of Hadassah Medical School, Hebrew University, Jerusalem, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by the Israeli Cancer Association. For full disclosures of all study authors, visit JAMA Oncology.
