Expert Point of View: Sibylle Loibl, MD

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Sibylle Loibl, MD

Sibylle Loibl, MD, of the German Breast Group and the Klinikum Offenbach in Germany, discussed the NeoALTTO findings at the European Cancer Congress, noting that this trial is one of several studies that all point to one conclusion: Pathologic complete response rates are lower in HER2-positive patients with PIK3CA mutations.

The GeparSixto study, for which Dr. Loibl was an investigator, found PIK3CA mutations in about 20% of HER2-positive tumors, including 22% of hormone receptor–positive patients and 16% in the negative group.1 The NeoSphere study found PIK3CA mutations in 32%, with no differences in frequency between the hormone receptor subgroups.2

In NeoSphere, however, the estrogen receptor–positive PIK3CA-mutant tumors had the lowest pathologic complete response rate, leading her to question whether the hormone subgroups do respond similarly, she said.

“But clearly, there is homogeneity demonstrated between studies, in that [pathologic complete response] rates are higher in wild-type than in PIK3CA-mutant cohorts,” she concluded. The difference is greatest in groups of HER2-positive patients receiving dual blockade, vs single agents.

Pathway Interactions

“The studies suggest the interaction of the different pathways, and the need to better select our HER2-positive patients for treatment,” Dr. Loible suggested, adding that other agents targeting PIK3CA might prove beneficial.

The addition of a PIK3CA inhibitor to anti-HER2 treatment in patients prescreened for the mutation prior to randomization is currently being evaluated in the phase II NeoPHOEBE trial. ■

Disclosure: Dr. Loibl reported no potential conflicts of interest.


1. Loibl S, Denkert C, Loi S, et al: PIK3CA mutations in primary HER2-positive and triple negative breast cancer. 2013 ASCO Annual Meeting. Abstract 11061. Presented June 3, 2013.

2. Gianni L, Bianchini G, Kiermaier A, et al: Neoadjuvant pertuzumab and trastuzumab: biomarker analyses of a 4-arm randomized phase II study (NeoSphere) in patients with HER2-positive breast cancer. 2011 San Antonio Breast Cancer Symposium. Abstract S51. Presented December 9, 2011.

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