Radiotherapy Cuts BRCA-Associated Contralateral Breast Cancer Risk
By Peter M. Goodwin
CHICAGO—Prophylactic contralateral (CLT) breast radiotherapy was associated with significantly fewer and delayed cases of breast cancer in women having standard therapy for their ipsilateral BRCA mutation-associated breast cancers in a study from Israel reported in a poster session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 514).
Ella Evron, MD, a medical oncologist at the Kaplan Medical Center in Zerifin, Israel, said that in Israel they saw many patients with BRCA-associated breast cancer because three “founder mutations” are commonly detected in Ashkenazi Jews who are at very high risk of developing breast cancer. “And once they get breast cancer they are also at very high risk of getting contralateral breast cancer,” she said.
And although risk-reducing mastectomy of the CLT breast was often recommended for these patients, Evron told Oncology Times that in Israel BRCA carriers mostly declined such surgery—especially because they feared disfiguring consequences and the impact mastectomy could have on body image, sexuality, and sensation. “And then they are left with a very high risk of contralateral cancer after being treated for their ipsilateral [disease],” she said.
But this reluctance to elect for surgery provided Evron and her colleagues with a pool of women at high risk for whom they could offer an alternative strategy for risk-reduction: contralateral breast radiotherapy. “Once they declined mastectomy, we would offer radiation therapy to the contralateral breast while [giving] radiation therapy to the ipsilateral diseased breast.”
And she said the women in her study divided roughly equally between those agreeing and disagreeing to CLT prophylactic radiotherapy. “If they would just opt for standard therapy, they would get lumpectomy and radiation therapy to the diseased breast and just close follow-up for the contralateral breast,” she said. “If they opted for bilateral radiation, they would get radiation to both breasts. It was not randomized. It was choice-driven.”
The researchers had a total of 162 patients of whom 81 had standard therapy and the remaining half had the same treatment but were also given radiation to the CLT breast.
At a median follow-up of 60 months, nine patients developed CLT breast cancer in the control group within a median of 24 months as compared to two patients in the intervention group who developed CLT breast cancer 80 and 109 months after bilateral breast irradiation.
One patient developed sarcoma in the muscle behind a CLT breast 5 years after bilateral irradiation. There was no increase in other early or late radiation toxicities among patients in the intervention group.
The researchers concluded that among BRCA carrier patients being treated for early breast cancer the addition of CLT breast irradiation significantly reduced risk of subsequent CLT breast cancer and constituted a viable option for high-risk women declining mastectomy.
Evron said the differences were statistically significant and that CLT irradiation not only reduced the numbers of events but also delayed them.
When she was asked for her view about the relative effectiveness of such prophylactic radiotherapy in comparison to the accepted method of prophylactic mastectomy, she referred to historical data. “About 1.5 percent of patients who had contralateral mastectomy still developed breast cancer,” she said, noting that prophylactic surgery was therefore still no guarantee of avoiding CLT breast cancer. “The results [with surgery] were comparable to our results. Although in our series the follow-up is still very early.”
Evron said it was necessary to wait longer to validate the prophylactic benefit of CLT breast radiotherapy, but she considered the method to be a promising new option. “I am hoping that if this is confirmed we would be able to offer patients who do not want to remove their breasts a preventive option that would reduce their risk of developing cancer.” Among genetically predisposed Jewish populations, she said this could be a very significant improvement.