The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis

Abstract

Studies to confirm the effect of acknowledged prognostic markers in older breast cancer patients are scarce. The aim of this study was to evaluate the prognostic value of HER-2 overexpression and PIK3CA mutations in older breast cancer patients. Female breast cancer patients aged 65 years or older, diagnosed between 1997 and 2004 in a geographical region in The Netherlands, with an invasive, non-metastatic tumour and tumour material available, were included in the study. The primary endpoint was relapse-free period and secondary endpoint was relative survival. Determinants were immunochemical HER-2 scores (0/1+, 2+ or 3+) and PIK3CA as a binary measure. Overall, 1698 patients were included, and 103 had a HER-2 score of 3+. HER-2 overexpression was associated with a higher recurrence risk (5 years recurrence risk 34 % vs. 12 %, adjusted p = 0.005), and a worse relative survival (10 years relative survival 48 % vs. 84 % for HER-2 negative; p = 0.004). PIK3CA mutations had no significant prognostic effect. We showed, in older breast cancer patients, that HER-2 overexpression was significantly associated with a worse outcome, but PIK3CA mutations had no prognostic effect. These results imply that older patients with HER-2 overexpressing breast cancer might benefit from additional targeted anti-HER-2 therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3734-y) contains supplementary material, which is available to authorised users.

Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients

“…These mutation frequencies may be underestimated. One possible reason is that most studies detected several exons with hotspot mutations via Sanger sequencing, spectrometry genotyping, or hydrolysis probe assays [4-13]. In the BOLERO-2 trial, tumor samples from 302 patients were analyzed via next-generation sequencing (NGS).…”

PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis

“…The association between PIK3CA mutations and HER2-positive breast cancer is still unclear, as previous studies have related PIK3CA mutations with unfavorable clinical outcomes [7811161719], favorable outcomes [18], or found no significant impact [121314152021]. Many studies that concluded that PIK3CA mutations corresponded with poor clinical outcomes found lower pCR rates in the mutant group than in the wild-type group [78111719], and in some cases, the difference was more pronounced in the ER-positive group [719].…”

“…Although the frequency of the mutation varies according to molecular subtype, this mutation has been described in approximately 12% to 39% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers [345678]. The PIK3CA mutation is being examined as a causative candidate for trastuzumab resistance in HER2-positive breast cancer due to the relevance of the PI3K/AKT pathway and HER2 [1910]; however, previous studies have been inconclusive [781112131415161718192021].…”

Modern methods of treatment of breast cancer in the elderly

“…Трастузумаб и пертузумаб, моноклональные антитела против Her2 рекомендованы для большинства пациентов с Her2 + РМЖ, при этом комбинация трастузумаба, пертузумаба и таксанов указана в качестве предпочтительного режима терапии первой линии для лечения Her2 + метастатического РМЖ [20]. Обнаружено, что используемый маркер Her2 также является серьезным прогностическим фактором рецидива у более пожилых пациенток с РМЖ [31], что сопоставимо с результатами исследований у более молодых пациентов. Анализы NCCN в рамках программы SEER-Medicare говорят о том, что пожилые пациенты, приступив к лечению по схемам с трастузумабом, с меньшей вероятностью, чем молодые женщины, способны завершить 1 год терапии [9,10].…”