Women with HER2-postive, hormone receptor–positive breast cancer and one or more mutations in PIK3CA were less likely to benefit from neoadjuvant chemotherapy and HER2-targeted therapies than those without a mutation, according to study results presented on December 12 at the 2013 San Antonio Breast Cancer Symposium in Texas.

Women with HER2-postive, hormone receptor (HR)–positive breast cancer and one or more mutations in PIK3CA were less likely to benefit from neoadjuvant chemotherapy and HER2-targeted therapies than those without a mutation, according to study results presented on December 12 at the 2013 San Antonio Breast Cancer Symposium in Texas.

PIK3CA is the second most common mutation in breast cancer and about 20% of primary breast cancers harbor a PIK3CA mutation,” said Sibylle Loibl, MD, professor at the German Breast Group in Neu-Isenburg, Germany. “We found that very few women with HER2-positive and HR-positive breast cancer with a PIK3CA mutation experienced a pathologic complete response [pCR] after receiving neoadjuvant therapy.”

Increasingly, data suggest that women who experience a pCR with drug therapy prior to surgery, meaning that they have no evidence of residual cancer in breast tissue and lymph nodes afterward, have a greater chance of long-term survival than women who do not have a pCR.

Loibl and her colleagues investigated whether a PIK3CA mutation affected the likelihood of experiencing a pCR following neoadjuvant therapy in 620 patients enrolled in the GeparQuinto (G5) and 595 patients enrolled in the GeparSixto (G6) clinical trials.

G5 trial participants received neoadjuvant chemotherapy (epirubicin and cyclophosphamide) with either trastuzumab (Herceptin; Genentech) or lapatinib (Tykerb; GlaxoSmithKline), both HER2-targeted therapies, for 24 weeks.

G6 trial participants received neoadjuvant chemotherapy (paclitaxel and nonpegylated-liposomal doxorubicin), either with or without the chemotherapy carboplatin, for 18 weeks. Those with HER2-positive disease also received neoadjuvant dual HER2 blockade with trastuzumab and lapatinib.

The differences in pCR rates were greatest among women who received the dual HER2 blockade (compared with a single anti-HER2 treatment). In these women, the rate of pCR was significantly lower among the group with HER2-positive disease who had at least one PIK3CA mutation in their tumor, compared with women without a PIK3CA mutation (17% vs. 37%). The effect was particularly striking among patients with HER2-positive, HR-positive disease, with just 6.3% of those with a PIK3CA mutation achieving a pCR compared with 30.8% for those without a PIK3CA mutation.

Loibl said that researchers need to identify new treatment options for patients with HER2-positive, HR-positive disease and evaluate them in clinical trials. “We also 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 added.