PIK3CA mutation predicted pCR in HER-2–positive breast cancer

PIK3CA, the second most common mutation in breast cancer, independently predicted pathologic complete response to neoadjuvant treatment among patients with HER-2–positive, hormone-receptor–positive breast cancer, according to results of two studies.

“PIK3CA-mutated tumors have a significantly lower pCR rate, and it seems especially low in those with a hormone receptor-positive status,” Sibylle Loibl, MD, professor at the German Breast Group in Neu-Isenburg, Germany, said during a press conference. “We need new treatment options for those patients.”

Loibl presented results of two clinical trials. In the GeparQuinto (G5)  trial, 620 patients were randomly assigned to either trastuzumab (Herceptin, Genentech) or lapatinib (Tykerb, GlaxoSmithKline) in combination with chemotherapy.

In the GeparSixto (G6)  trial, 595 patients received trastuzumab and lapatinib  plus a taxane anthracycline and chemotherapy, and some were randomly assigned to also receive carboplatin.

“In the mutated cohort, there is no difference between the treatments,” she said. “The patients with wild-type status seem to derive a benefit from trastuzumab or a combination of the two agents, but there is no difference in the lapatinib-treated cohort. They [demonstrated] the same pCR rate, irrespective of the mutation.”

Hormone receptor status of mutated tumors played a role in pCR in the G6 study, Loibl said.

There was no difference of prevalence of hormone receptor status when looking at detectable PIK3CA mutations in HER-2­–positive breast cancers in either study (21% in both), but pCR increased for those patients who were classified as wild type in the G6 study.

Researchers reported pCR of 22% in patients with mutations vs. 42% in patients without mutations (P=.001). The effect was significant among those who were HER-2–positive. In that group, pCR was 17% for patients with the mutation vs. 37% for those without (P=.015).

Among patients with HER-2–positive, hormone receptor-positive breast cancer, the rate of pCR was 6.3% among those with the mutation vs. 30.8% among those without the mutation (P=.005). Researchers reported no difference in pCR based on mutation status among HER-2–positive, hormone receptor-negative patients (P=.825).

The results are in agreement with those of the NeoSPHERE and NeoALTTO trials, Loibl said.

“We need to integrate PIK3CA mutation analysis of breast tumors into routine practice so that we can ensure women receive the most appropriate neoadjuvant therapy for their tumor type,” Loibl said.

For more information:
Loibl S. Abstract #S4-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.

Disclosure: The study was supported by the European Commission’s Seventh RTD Framework Programme grant #278659 RESPONSIFY. Loibl reports no relevant financial disclosures.