Prognostic value of PAM50 in residual breast cancer following neoadjuvant endocrine therapy (NET): A retrospective analysis with long follow-up.

Authors

Miguel Gil Gil

Miguel J. Gil Gil

Breast Cancer Unit & Medical Oncology Department, Institut Català d'Oncologia, IDIBELL, Barcelona, Spain

Miguel J. Gil Gil , Francisco Javier Perez , Teresa Soler Monso , Tomas Pascual , Patricia Galván , Laia Pare , Anna Petit , Catalina Falo , Agostina Stradella , María Jesús Pla , Ramon Salazar , Aleix Prat

Organizations

Breast Cancer Unit & Medical Oncology Department, Institut Català d'Oncologia, IDIBELL, Barcelona, Spain, Clinical Research Unit, Institut Català d'Oncologia, Barcelona, Spain, Bresat Cancer Unit & Pathology Department, Hospital de Bellvitge, Barcelona, Spain, Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain, Department of Medical Oncology, Hospital Clínic de Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain, Breast Cancer Unit & Pathology Department. Hospital de Bellvitge, Barcelona, Spain, Breast Cancer Unit Medical Oncology Department. Institut Català D'Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain, Breast Cancer Unit, Department of Medical Oncology, Institut Català d'Oncologia, Barcelona, Spain, Breast Cancer Unit & Gynecology Department, Hospital de Bellvitge, Barcelona, Spain, Medical Oncology Department. Institut Català D'Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain, Department of Medical Oncology, Hospital Clínic de Barcelona. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS). SOLTI Breast Cancer Cooperative Group, Barcelona, Spain

Research Funding

Other

Background: NET is gaining more acceptances for the management of hormonal receptors (HR)-positive breast cancer (BC). To date, the decrease of Ki-67 and PEPI score are the only prognostic factors associated with relapse-free survival after NET. PAM50 is a validated prognostic test in newly diagnosed BC; however, its value in residual tumors after NET is currently unknown. Methods: We took tumor tissues from patients of a retrospective study of 119 postmenopausal women with HR-positive stage II-III BC. Patients were diagnosed from 1997 to 2009 and were treated with NET for a median duration of 8.5 months. Median age was 74 (63-88). After NET all patients underwent surgery (73% conservative). Adjuvant treatment were endocrine therapy in 100%, radiotherapy in 76.5% and chemotherapy 7%. Median follow-up from surgery was 112 months. Median follow-up from surgery was 112 months. We observed 26 (24%) of distant relapses and 75 deaths (44 without cancer). Median overall survival was 134.8 months. RNA was extracted from FFPE tumor tissues of surgical specimens. A panel of 55 BC-related genes, including the research-based PAM50 assay (subtypes, ROR-S and ROR-P pre-defined cutpoints), androgen receptor (AR), immune genes (CD8A, CD4, PDL1 and PD1). Uni- and multi-variable Cox models were used to evaluate the association of each variable with distance recurrence free interval (DRFI). Results: PAM50 subtype distribution: Luminal A 54.3%, Normal-like 24.3%; HER2-enriched 16,5%, Luminal B 1% and basal 1%. Distribution of ROR-S groups was Low 64%, medium 30%and high 6%. Distribution of PEPI score was: 0 in 43%, 3 in 37% and 6 in 20%. Among the different variables explored, PEPI score 0 (HR 0.27 [95%IC 0.09-0.79] p=0.001), low ROR-S (HR 0.39 [95%CI 0.17-0.91] p=0.001) and high AR expression (HR 0.71 [95CI 0.53-0.96] p=0.007) were significantly associated with lower DRFI in univariate analyses. After adjusting for PEPI (with or without Normal-like tumors), ROR-S and AR remained significantly associated with outcome. Conclusions: PAM50 ROR-S and AR expression in residual tumors after NET provide independent prognostic information beyond PEPI. With further validation, these biomarkers could help clinicians in the decision-making of adjuvant chemotherapy.

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Neoadjuvant Therapy

Citation

J Clin Oncol 37, 2019 (suppl; abstr 575)

DOI

10.1200/JCO.2019.37.15_suppl.575

Abstract #

575

Poster Bd #

67

Abstract Disclosures

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