Patients With PIK3CA Mutations Less Likely to Benefit From Dual Anti-HER2 Inhibition

Share this content:

the Cancer Therapy Advisor take:

PIK3CA mutations were identified as possible predictive biomarkers of resistance to dual anti-human epidermal growth factor 2 (HER2) treatment for patients with breast cancer, according to an article published online in the journal The Oncologist.

Participants in this study included 121 patients with breast cancer who were positive for HER2. These patients were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib.

The investigators collected pre- and post-treatment samples and evaluated them for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations.

Results showed 20% of the cases had a mutation in PIK3CA exon 20 or 9. Pathologic complete remission (pCR) rates were determined to be similar in PIK3CA wild-type (33.3%) and PIK3CA-mutated patients (22.7%; P=0.323).

Patients with PIK3CA wild-type tumors who were administered trastuzumab plus lapatinib experienced a higher probability of pCR (48.4% vs. 12.5%; P=0.06).

Furthermore, Ki67, pAKT, and apoptosis mutations were significantly decreased from baseline, as measured from the residual disease. Patients who received the dual anti-HER2 blockade demonstrated significantly greater degrees of Ki67 inhibition.

The gene expression and copy number data analysis revealed that a 50-gene signature specifically predicted pCR induced by lapatinib.

Paradigm Shift: There's More to Tumor Drug Resistance Than Just Gene Mutations
PIK3CA mutations possible predictive biomarkers of resistance to dual anti-human epidermal growth factor 2 treatment in breast cancer.
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Division of Medical Oncology 2, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy; Division of Oncology, University Hospital, Ferrara, Italy; Division of Pathology, Modena University Hospital, Modena, Italy; Center for Genome Research, University

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs