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4P - Independent validation of the PAM50-based chemoendocrine score (CES) as pathologic complete response (pCR) and disease-free survival (DFS) predictor in hormone receptor (HR)+/HER2+ breast cancer (BC)


24 May 2020




Tomas Pascual


Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117


T. Pascual1, A. Fernandez-Martinez1, M. Tanioka1, M.V. Dieci2, S. Pernas Simon3, J. Gavila Gregori4, V. Guarneri5, J. Cortés6, P. Villagrasa7, M.J. Vidal8, B. Adamo8, M. Muñoz8, G. Griguolo9, A. Llombart Cussac10, A.M. Antunes De Melo e Oliveira11, L. Paré7, L.A. Carey12, C.M. Perou1, A. Prat8

Author affiliations

  • 1 Genetics Department, UNC Lineberger Comprehensive Cancer Center - University of North Carolina at Chapel Hill, 27514 - Chapel Hill/US
  • 2 Medical Oncology 2 Dept., Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 3 Dept. Medical Oncology, Institut Catala d’ Oncologia, 08908 - Hospitalet de Llobregat/ES
  • 4 Medical Oncology Department, IVO - Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 5 Department Of Surgery, Oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 6 Dept. Medical Oncology, IOB Institute of Oncology, Quiron group, 08023 - Barcelona/ES
  • 7 Dept. Scientific, SOLTI Breast Cancer Research Group, 08008 - Barcelona/ES
  • 8 Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, Translational Genomics and Targeted Therapeutics Group (IDIBAPS), 08036 - Barcelona/ES
  • 9 Medical Oncology Department, IOV - Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 10 Medical Oncology, Hospital Universitario Arnau de Vilanova, Universidad Catolica, 46015 - Valencia/ES
  • 11 Dept. Medical Oncology, Vall d' Hebron University Hospital;; Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 12 Medicine - Hematology/oncology Division, UNC - The University of North Carolina at Chapel Hill - School of Medicine, 27599 - Chapel Hill/US

Abstract 4P


HR+/HER2+ BC is heterogeneous and there is a need to identify predictive biomarkers. We previously reported the ability of the PAM50-based CES to predict chemoendocrine sensitivity in HR+/HER2-negative BC beyond intrinsic subtype and risk of relapse (ROR) (Prat.CCR.2017). Here we evaluate the association of CES with pCR and DFS following different anti-HER2 combinations in HR+/HER2+ BC.


Intrinsic subtype and clinicopathologic data were obtained from 8 independent studies for a total of 485 HR+/HER2+ early BC. Patients (pts) were treated with anti-HER2 therapy either with endocrine therapy (PAMELA and PER-ELISA) or with chemotherapy (CHERLOB, OptiHER, LPT109096, ICO, HCB, PER-ELISA and CALGB 40601 [Alliance]). CES was evaluated as a continuous variable and categorically (CES-E [endocrine-sensitive], CES-U [uncertain] and CES-C [chemosensitive]) using previously reported cutoffs. We first performed statistical analyses in each dataset individually, and then all 8 combined. Multivariable analyses were used to test the association of the CES score with pCR and DFS.


In the combined cohort, CES-E, CES-U and CES-C were identified in 16%, 22% and 62% of the pts, respectively. CES (continuous variable) was associated with higher pCR rates independent of clinical characteristics, treatment type, intrinsic subtype and study (adjusted Odd Ratio [OR]=0.42; p = 0.02). In the PER-ELISA trial, CES was also found associated with response (decrease in ki67) following 2 weeks of letrozole alone (OR=29.1, p 0.01). 295 pts (CHERLOB, ICO, HCB and CALGB40601) were analyzed for DFS with a median follow-up of 66 months (IQR 37-82). The adjusted DFS hazard ratio of the CES (continuous variable) was 0.13 (p < 0.01) independent of pCR, clinical characteristics, ROR and intrinsic subtype. In pts without pCR, disease recurrence occurred in 4% of CES-E, 19% of CES-U and 34% of CES-C pts (p < 0.01).


In HR+/HER+ BC, CES shows clinical validity for predicting chemoendocrine sensitivity in combination with anti-HER2 targeted therapies and is a good prognostic factor beyond intrinsic subtype and clinicopathologic characteristics.

Clinical trial identification

CALGB-40601: NCT00770809; Per-ELISA: NCT02411344; SOLTI-PAMELA: NCT01973660; SOLTI-Opti-HER:NCT01669239; LPT109096: NCT00524303; CHERLOB: NCT00429299.

Editorial acknowledgement

Legal entity responsible for the study

Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS).


Becas FSEOM para Formación en Investigación en Centros de Referencia en el Extranjero 2018 (TP). Fundación SEOM, Becas FSEOM para Formación en Investigación en Centros de Referencia en el Extranjero 2016 (AF-M). Conquer Cancer Foundation -YIA in Breast Cancer 2019 (GG). BCRF, Susan G Komen, NCI SPORE (P50-CA58823), R01-CA229409 and Alliance U10CA180821(LAC, CMP). Instituto de Salud Carlos III - PI16/00904 (AP), Pas a Pas (AP), Save the Mama (AP), Breast Cancer Now - 2018NOVPCC1294 (AP).


M.V. Dieci: Honoraria (self): Genomic Health; Honoraria (self): Eli Lilly; Honoraria (self): Celgene. S. Pernas Simon: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Polyphor; Advisory/Consultancy: TFS. J. Gavila Gregori: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: MSD Oncology. V. Guarneri: Honoraria (self): Eli Lilly; Honoraria (self): Roche/Genentech; Honoraria (self): Novartis. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString Technologies. M.J. Vidal: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer. M. Oliveira: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Immunomedics; Honoraria (self), Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Boehringer-Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): PUMA Biotechnology; Research grant/Funding (institution): Zenith Epigenetics; Travel/Accommodation/Expenses: Pierre-Fabre; Travel/Accommodation/Expenses: GP Pharma; Travel/Accommodation/Expenses: Grünenthal; Travel/Accommodation/Expenses: Eisai. C.M. Perou: Advisory/Consultancy, Shareholder/Stockholder/Stock options: BioClassifier LLC; Licensing/Royalties: Breast PAM50 assay. A. Prat: Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): MSD Oncology; Honoraria (self): Lilly; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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