PIK3CA Mutations Associated With Lower Rate of Pathologic Complete Response to Neoadjuvant Anti-HER2 Therapy in Breast Cancer
In a study reported in the Journal of Clinical Oncology, Loibl et al found that PIK3CA mutation was associated with lower pathologic complete response rate in patients with HER2-positive breast cancer receiving trastuzumab (Herceptin), lapatinib (Tykerb), or both in addition to neoadjuvant anthracycline-taxane chemotherapy. There was no difference in disease-free or overall survival between patients with mutant vs wild-type PIK3CA.
The study involved data from 504 HER2-positive patients from the neoadjuvant GeparQuattro, GeparQuinto, and GeparSixto studies in whom PIK3CA mutation status could be determined. All patients received trastuzumab (34%), lapatinib (18%), or the combination (48%), plus anthracycline-taxane chemotherapy.
Lower Pathologic Complete Response Rates
PIK3CA mutations were found in 21.4% of patients. Rates of pathologic complete response were 19.4% in patients with PIK3CA mutation vs 32.8% in those with wild-type PIK3CA (odds ratio [OR] = 0.49, P = .008). Among 291 patients with hormone receptor–positive tumors, pathologic complete response rates were 11.3% vs 27.5% (OR = 0.34, P = .011). In 213 patients with hormone receptor–negative tumors, pathologic complete response rates were 30.4% vs 40.1% (OR = 0.65, P = .233; P = .292 for interaction). In a multivariable analysis adjusting for age, tumor stage, nodal status, histologic type, tumor grade, study, and anti-HER2 treatment, presence of PIK3CA mutation was independently predictive of lower likelihood of pathologic complete response (OR = 0.49, P = .01).
Pathologic complete response rates were 16.0% with lapatinib, 24.3% with trastuzumab, and 17.4% with the combination (P = .654) in patients with PIK3CA mutation and 18.2%, 33.8%, and 37.1% (P = .017), respectively, in those with wild-type PIK3CA.
Survival
There were no significant differences in disease-free survival (hazard ratio [HR] = 1.07, P = .854) or overall survival (HR = 0.59, P = .219) between patients with vs without PIK3CA mutation.
The investigators concluded: “HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a [pathologic complete response] after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given….Our data suggest that investigation of alternative therapies (such as a PI3K inhibitor) in PIK3CA-mutant HER2-positive breast cancers is warranted.”
Sibylle Loibl, MD, PhD, of the German Breast Group, Neu-Isenburg, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Seventh Research and Technological Development Framework Programme. For full disclosures of the study authors, visit jco.ascopubs.org.
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