PIK3CA Mutations Are Associated With Lower Rates of Pathologic Complete Response to Anti–Human Epidermal Growth Factor Receptor 2 (HER2) Therapy in Primary HER2-Overexpressing Breast Cancer

Abstract

HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given.

1976 Significance of PIK3CA mutations in patients with early breast cancer treated with adjuvant chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) study

“…Our PIK3CA mutation rate (23.3%) was consistent with the literature, as well as our rate of different hotspot mutations [3,14,19,[22][23][24][25][26][27][28][29][30][31][32][33][34]. Also, we confirmed significant associations of different types of PIK3CA mutations with clinicopathological and molecular characteristics.…”

“…Notably, many studies examining the prognostic significance of PIK3CA mutations in breast cancer [35] have been published, however very few included a large enough number of patients [3,14,19,[22][23][24][25][26][27][28][29][30][31][32][33][34]. Also, less than half of them [22,24,26,28,30,31,33] used data from clinical trials, thus excluding the effect of treatment heterogeneity when evaluating prognostic factors. Up to now, results are largely inconclusive with some studies showing favorable and other adverse impact of PIK3CA mutations on patient outcome, while a significant number of reports did not show any prognostic significance.…”

Association of PIK3CA Mutation Status before and after Neoadjuvant Chemotherapy with Response to Chemotherapy in Women with Breast Cancer

“…However, few studies have investigated the association between PIK3CA mutations and the response to neoadjuvant chemotherapy in breast cancer (19,34,35). Therefore, whether breast cancer patients with PIK3CA mutations are sensitive to neoadjuvant chemotherapy is not fully determined.…”

“…2, 7-11). All three hotspot mutations are oncogenic and constitutively activate the PI3K pathway (3,(12)(13)(14)(15)(16)(17)(18)(19)(20). The remaining mutations are distributed over the entire PIK3CA-coding sequence.…”

General St. Gallen-2015 guidelines for the treatment of early breast cancer (adapted by the experts of the Russian Society of Breast Oncologists)

“…Частота pCR была выше у пациентов, в опухолях которых отмечалась лимфоцитарная инфильтра-ция, или трижды негативный, или HER-2-позитивный РМЖ, получавших лечение карбоплатином [77,78]. В нескольких исследованиях неоадъювантной терапии было показано, что у пациентов с мутацией PIK3CA, получавших анти-HER-2-терапию, отмечалась более низкая частота pCR [82][83][84]. Неоадъювантная эндокринотерапия, как правило, требует больше времени для достижения ответа опухоли; лечение может быть продолжено до достижения максимального ответа [85].…”