Association between PIK3CA activating mutations and outcomes in early-stage invasive lobular breast carcinoma treated with adjuvant systemic therapy

Author:

Ribnikar Domen12,Horvat Valentina Jeric1,Ratosa Ivica23,Veitch Zachary W4,Grcar Kuzmanov Biljana5,Novakovic Srdjan6,Langerholc Erik7,Amir Eitan8,Seruga Bostjan12

Affiliation:

1. Department of Medical Oncology , Institute of Oncology Ljubljana , Ljubljana , Slovenia

2. Faculty of Medicine Ljubljana , University of Ljubljana , Ljubljana , Slovenia

3. Department of Radiation Oncology , Institute of Oncology Ljubljana , Ljubljana , Slovenia

4. Division of Medical Oncology and Hematology , Royal Victoria Hospital , Bariie , Ontario , USA

5. Department of Pathology , Institute of Oncology Ljubljana , Ljubljana , Slovenia

6. Department of Molecular Diagnostics , Institute of Oncology Ljubljana , Ljubljana , Slovenia

7. Institute of Biostatistics and informatics, Faculty of Medicine Ljubljana , University of Ljubljana , Ljubljana , Slovenia

8. Division of Medical Oncology and Hematology , University of Toronto and Princess Margaret Cancer Centre , Toronto , Canada

Abstract

Abstract Background The aim of the study was to evaluate the independent prognostic role of PIK3CA activating mutations and an association between PIK3CA activating mutations and efficacy of adjuvant endocrine therapy (ET) in patients with operable invasive lobular carcinoma (ILC). Patients and methods A single institution study of patients with early-stage ILC treated between 2003 and 2008 was performed. Clinicopathological parameters, systemic therapy exposure and outcomes (distant metastasis-free survival [DMFS] and overall survival [OS]) were collected based on presence or absence of PIK3CA activating mutation in the primary tumor determined using a quantitative polymerase chain reaction (PCR)-based assay. An association between PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival analysis, whereas an association between PIK3CA mutation and ET was analyzed in estrogen receptors (ER) and/or progesterone receptors (PR)-positive group of our patients by the Cox proportional hazards model. Results Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among 365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associated with differential DMFS and OS (p = 0.36 and p = 0.42, respectively). In patients with PIK3CA mutation each year of tamoxifen (TAM) or aromatase inhibitor (AI) decreased the risk of death by 27% and 21% in comparison to no ET, respectively. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET had a favourable impact on OS. Conclusions PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC. Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether they received TAM or an AI.

Publisher

Walter de Gruyter GmbH

Subject

Radiology, Nuclear Medicine and imaging,Oncology

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