PIK3CA Mutations in HER2-Positive Breast Cancer

Panelists: Kimberly L. Blackwell, MD, Duke; Adam M. Brufsky, MD, PhD, University of Pittsburgh;
Joyce A. O’Shaughnessy, MD, US Oncology; Mark D. Pegram, MD, Stanford; Hope S. Rugo, MD, UCSF;
Denise A. Yardley, MD, Sarah Cannon
Published Online: Monday, February 10, 2014
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Certain mutations in the PI3 kinase pathway seem to influence sensitivity to HER2-targeted therapy, explains Mark D. Pegram, MD. These findings were initially supported by a biomarker analyses from the four-arm NeoSphere trial that examined pertuzumab plus trastuzumab with docetaxel in newly diagnosed patients with HER2-positive early-stage breast cancer.

Overall, this analysis did not show a significant different between PIK3CA-mutant and wild type, in terms of variation in pathologic complete response (pCR). However, when examining patients with PIK3CA exon 9 mutations only 2 out of 28 had a pCR, Pegram states. Moreover, 0 out of 4 patients with PIK3CA exon 7 mutations had a pCR. This information suggests these mutations have a deleterious effect, even for patients receiving pertuzumab, Pegram states.

Interestingly, Pegram notes, a biomarker analyses from the phase III EMILIA trial did not find an association between PIK3CA mutations and resistance for women with HER2-positive metastatic breast cancer treated with T-DM1. This same analysis found that PIK3CA mutations negatively impacted the efficacy of lapatinib plus capecitabine. This data seems to suggest that T-DM1 might overcome the deleterious impact of PIK3CA mutations, Pegram believes.

The overall analysis would suggest that patients with PIK3CA mutations still benefit from treatment with pertuzumab, notes Joyce A. O’Shaughnessy, MD. This may indicate that pertuzumab impacts the PI3 kinase pathway more than lapatinib, which may have a greater impact on the HER1/ERK pathway.

There are several ongoing clinical trials exploring treatments for HER2-positive breast cancer, including APHINITY, ALTTO, and NeoALTTO, explains Adam M. Brufsky, MD, PhD. The phase III randomized KAITLIN study (BO28407) will compare T-DM1 plus pertuzumab to trastuzumab with pertuzumab plus a taxane as adjuvant therapy following anthracyclines for patients with HER2-positive primary invasive breast cancer.
View More From This Discussion
Episode 1 Overview of HER2-Targeted Therapies in Breast Cancer
Episode 2 Treating Low-Risk HER2-Positive Breast Cancer
Episode 3 Frontline Pertuzumab for Metastatic Breast Cancer
Episode 4 PIK3CA Mutations in HER2-Positive Breast Cancer
Episode 5 T-DM1 in HER2-Positive Metastatic Breast Cancer
Episode 6 Recommendations for Optimal HER2 Testing in Breast Cancer
Episode 7 Role of Lapatinib in HER2-Positive Breast Cancer
Episode 8 Novel Drug Development in Breast Cancer
Episode 9 Phase III Clinical Trials in HER2-Positive Breast Cancer
Episode 10 Case Study: HER2-Positive Oligometastatic Breast Cancer
Episode 11 Upfront Treatment of HR-Positive MBC
Episode 12 Next Steps for Everolimus in Metastatic Breast Cancer
Episode 13 CDK4/6 Inhibitors in Metastatic Breast Cancer
Episode 14 Chemotherapeutics in Metastatic Breast Cancer
Episode 15 Preventing Skeletal-Related Events in Breast Cancer
Episode 16 Conclusion: Future Direction of Breast Cancer Treatment
Expert Panelists
Dr Adam Brufsky

Adam M. Brufsky, MD, PhD

Professor of Medicine, University of Pittsburgh
Medical Director of the Women’s Cancer Center at Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania

Kimberly L. Blackwell, MD

Professor of Medicine
Assistant Professor in Radiation Oncology
Duke Cancer Institute
Durham, North Carolina

Joyce A. O’Shaughnessy, MD

Co-Director, Breast Cancer Research
Baylor Charles A. Sammons Cancer Center
Texas Oncology, PA/US Oncology,
Dallas, Texas

Mark D. Pegram, MD

Professor of Medicine (Oncology)
Stanford University Medical Center;
Susy Yuan-Huey Hung Professor;
Associate Director of Clinical Research and Director, Breast Cancer Program, Stanford Cancer Institute, Stanford, California

Hope S. Rugo, MD

Professor of Medicine and Director of the Breast Oncology, Clinical Trials, and Education Program, University of California San Francisco Comprehensive Cancer Center, San Francisco, California

Denise A. Yardley, MD

Senior Investigator, Breast Cancer Research
Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Tennessee
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