Induction of PIK3CA alterations during neoadjuvant letrozole may improve outcome in postmenopausal breast cancer patients
| Autor: | Maj-Britt Jensen, Lise Barlebo Ahlborn, Jens-Ole Eriksen, Signe Korsgaard Skriver, Anne Vibeke Lænkholm, Ann Knoop, Bent Ejlertsen, Maria Rossing |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Neuroblastoma RAS viral oncogene homolog Cancer Research medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases Estrogen receptor Breast Neoplasms PDGFRA medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Biomarkers Tumor medicine Humans ERBB3 neoplasms business.industry Letrozole Cancer medicine.disease Neoadjuvant Therapy Postmenopause 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female KRAS business medicine.drug |
| Zdroj: | Breast Cancer Research and Treatment. 184:123-133 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-020-05833-w |
| Popis: | Estrogen receptor positive (ER+) breast cancer constitutes almost 85% of all breast cancer patients and are a genetically highly heterogenic group. Data on the association of somatic alterations to outcome and prognosis are however sparse. In this neoadjuvant endocrine phase II trial including postmenopausal breast cancer patients with ER+, HER2 normal breast cancer, we investigated the rate of pathogenic mutations before and after treatment as well as the association with treatment response and survival. Pretreatment and posttreatment tumour samples from 109 patients treated with neoadjuvant letrozole were collected and analysed with Next Generation Sequencing utilizing a panel of 12 genes (ALK, BRAF, EGFR, ERBB2, ERBB3, ESR1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, and RAF1). Residual disease was assessed by a modified Miller Payne scale and the Residual Cancer Burden index. Survival data were collected prospectively. Among the 109 patients, 52 had at least one pathogenic mutation in the pretreatment sample and 60 in the posttreatment sample. The most frequently mutated gene was PIK3CA, followed by EGFR and KRAS. Twelve different pathogenic PIK3CA mutations were identified, primarily in exon 20 and exon 9. An altered PIK3CA mutation profile from the pre- to the posttreatment specimen was significantly associated to improved pathological outcome. Overall and Disease-Free Survival benefits in PIK3CA mutated patients was observed. Considerable heterogeneity was identified both among patients and between pre- and posttreatment samples. PIK3CA has the potential to be a predictive biomarker. To further assess the implications of a treatment related altered PIK3CA mutation profile, more data are needed. |
| Databáze: | OpenAIRE |
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