PIK3CA Mutations Implicated in Treatment-Resistance for Some Breast Cancers

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PIK3CA Mutations Implicated in Treatment-Resistance for Some Breast Cancers
PIK3CA Mutations Implicated in Treatment-Resistance for Some Breast Cancers

SAN ANTONIO—Some hormone receptor–positive, HER2-positive breast tumors' resistance to presurgical chemotherapy and HER2-targeted therapy is associated with mutations in the PIK3CA gene, according to a study presented at the 2013 San Antonio Breast Cancer Symposium.

“We found that very few women with HER2-positive and hormone receptor–positive breast cancer with a PIK3CA mutation experienced a pathologic complete response (pCR) after receiving neoadjuvant therapy,” reported Sibylle Loibl, MD, professor of the German Breast Group in Neu-Isenburg, Germany.

PIK3CA mutations occur in approximately 20% of HER2-positive tumors overall and “are among the most common genetic aberrations in breast cancer,” she noted.

The researchers prospectively evaluated PIK3CA mutations in 512 participants of the neoadjuvant Geparsixto (G6) clinical trial and 225 participants in the GeparQuinto (G5) trial, and analyzed whether mutation status affected pCR rates following neoadjuvant therapy.

Patients with HER2-positive tumors were more likely to have PIK3CA mutations than were women with triple-negative breast cancer (TNBC), the researchers found.

Overall, women whose tumors harbored at least one PIK3CA mutation saw lower pCRs, but this finding was statistically significant only among women with HER2-positive and hormone receptor–positive tumors, Dr. Loibl noted. pCR rates were significantly lower among HER2-positive tumors harboring PIK3CA mutations than those without mutations (22.7% vs. 43.6%; P = 0.001). Mutation status predicted pCR for patients with HER2-positive but not TNBCs (17.8% vs. 36.8%; P = 0.015 for HER2-positive with double HER2 blockade; TNBC: 33.3% vs. 49% pCR; P = 0.168, not significant), Dr. Loibl reported.

“Within the HER2-positive/HR-positive subgroup the [patients with] PIK3CA [mutation] had a pCR rate of only 6.5% compared with 30.8% in the wild type (non-mutant) group (P = 0.005),” Dr. Loibl noted. “In contrast, there was no difference in pCR (42.9% vs. 46.1%) according to PIK3CA mutation status in the HER2-positive/HR-negative group” (P = 0.825, not significant).

Data from the phase 3 GeparQuinto (trastuzumab or lapatinib monotherapy) clinical trial are now undergoing analysis to evaluate the role of PIK3CA mutations in women receiving only one HER2 treatment, Dr. Loibl said.

Researchers “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,” she said.

“I think we need new treatment options for these patients,” she said.


  1. Loibl S et al. S4-06. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.

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