NEW YORK – Researchers have homed in on BRCA1/2 mutations as a potential biomarker predictive of which early-stage breast cancer patients will respond to a neoadjuvant chemotherapy regimen containing epirubicin, paclitaxel, cyclophosphamide (iddEPC).
Esther Pohl-Rescigno from University Hospital Cologne in Germany led the study published in JAMA Oncology last week. The secondary analysis was based on the 961-patient Phase III GeparOcto trial, which previously investigated the sequential use of intense, dose-dense iddEPC and weekly paclitaxel/liposomal doxorubicin with or without carboplatin (PM(Cb)). In 2017, researchers reported that patients had a 48.3 percent pathological complete response (pCR) rate on the iddEPC regimen and a pCR of 47.6 percent with PM(Cb).
In the triple-negative breast cancer cohort, pCR was 48.5 percent with iddEPC and 51.7 percent with PM(Cb). For patients with HER2-positive cancer, pCR was 62.0 percent with iddEPC and 57.4 percent with PM(Cb). And in the Luminal B breast cancer cohort, pCR was 14.1 percent with iddEPC and 14.6 percent with PM(Cb).
The JAMA study researchers wanted to follow-up on these prior findings and further decipher whether patients' responses to these chemotherapy regimens differed based on if they harbored germline mutations in BRCA1/2 and other breast cancer risk genes.
Pohl-Rescigno and colleagues found that overall pCR rates were higher in patients with BRCA1/2 germline cancer risk variants than in patients without such mutations (60.4 percent vs 46.7 percent).
There was no association between participants' treatment responses and whether they had variants in other cancer risk genes such as ATM, CHEK2, FANCM, PALB2.
TNBC patients with BRCA1/2 germline variants had the highest pCR rates. Positive BRCA1/2 variant status was associated with a 74.3 percent response in the PMCb arm versus 47 percent response in patients without BRCA1/2 variants. In the iddEPC arm, response among patients with positive germline BRCA 1/2 status was 64.7 percent compared to 45 percent in those without the variants.
The researchers also found that ERBB2-negative, hormone receptor-positive breast cancer patients with positive BRCA1/2 variant status had a higher pCR rate than those without BRCA 1/2 variants (31.8 percent vs 11.9 percent).
"Effective chemotherapy for BRCA 1/2-mutated TNBC is commonly suggested to be platinum based. With a pCR rate of 64.7 percent, iddEPC may also be effective in these patients, though further prospective studies are needed," Pohl-Rescigno et. al wrote. "The elevated pCR rate in BRCA1/2-mutated ERBB2-negative, hormone receptor–positive breast cancer suggests that germline BRCA1/2 testing should be considered prior to treatment start."