Meeting
2019 ASCO Annual Meeting
PAM50 HER2-enriched subtype as an independent prognostic factor in early-stage HER2+ breast cancer following adjuvant chemotherapy plus trastuzumab in the ShortHER trial.
Authors
Pier Franco Conte
Department of Surgery, Oncology and Gastroenterology, University of Padova, Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
Pier Franco Conte , Gaia Griguolo , Maria Vittoria Dieci , Giancarlo Bisagni , Alba Ariela Brandes , Antonio Frassoldati , Luigi Cavanna , Antonino Musolino , Francesco Giotta , Anita Rimanti , Ornella Garrone , Patricia Galvan , Fara Brasó Maristany , Enrico Orvieto , Loredana Urso , Antonino Maiorana , Sara Balduzzi , Roberto D'Amico , Valentina Guarneri , Aleix Prat
Organizations
Department of Surgery, Oncology and Gastroenterology, University of Padova, Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy, Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy, Oncology Unit, Department of Oncology and Advanced Technologies, Azienda USL-IRCCS, Reggio Emilia, Italy, Medical Oncology, Azienda Unita` Sanitaria Locale di Bologna-IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy, Clinical Oncology, Department of Morphology, Surgery and Experimental Medicine, S Anna University Hospital, Ferrara, Italy, Department of Oncology-Hematology, G. da Saliceto Hospital, Piacenza, Italy, University Hospital of Parma, Medical Oncology and Breast Unit, Parma, Italy, Division of Medical Oncology, IRCCS, Istituto Tumori “Giovanni Paolo II”, Bari, Italy, Medical Oncology, Azienda Ospedaliera di Mantova, Mantova, Italy, Medical Oncology, A.O. S. Croce and Carle Teaching Hospital, Cuneo, Italy, Department of Medical Oncology, Hospital Clínic de Barcelona. Translational Genomics and Targeted Therapeutics in Solid Tumours Lab (IDIBAPS), Barcelona, Spain, Department of Medical Oncology, Hospital Clínic de Barcelona. Translational Genomics and Targeted Therapeutics in Solid Tumours Lab (IDIBAPS), Barcelona, Italy, Pathology, Ulss 5 Polesana, Rovigo, Italy, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy, Department of Diagnostic Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy, Department of Surgery, Oncology and Gastroenterology, University of Padua, Medical Oncology 2, Instituto Oncologico Veneto IRCCS, Padova, Italy, 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
Biomarkers analysis of ShortHER study (5x1000 programme, Istituto Oncologico Veneto, Padova, Italy); Istituto de Salud Carlos III (ISCIII) through Plan Estatal de Investigation Cientifica y Tecnica y de Innovacion 2013-2016 (PI16/00904); Breast Cancer Now
Background: We investigated the prognostic role of the PAM50 HER2-enriched (HER2-E) subtype in HER2+ early breast cancer enrolled in the randomized Phase III ShortHER trial. Methods: The ShortHER study randomized 1254 HER2+ early breast cancer patients to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy. Gene expression measured using nCounter platform was available for 438 surgical samples. Intrinsic subtyping was determined using the research-based PAM50 predictor. Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death (median follow up 72 months). Uni- and multi-variable analysis were performed using Cox models. Results: PAM50 subtype distribution was: HER2-E 53% (N = 233), Luminal A 20% (N = 87), Luminal B 10% (N = 43), Normal-like 11% (N = 48) and Basal-like 6% (N = 27). HER2-E subtype was associated with hormone receptor-negative status (p < 0.001) and TILs ≥20% (p < 0.001), but not with stage and age ( < or ≥60 yrs). HER2-E subtype was associated with worse MFS vs other PAM50 subtypes overall (HR 2.78, p = 0.001), in the short (HR 2.24, p = 0.046), and in the long arm (HR 4.04, p = 0.011). Multivariable Cox model confirmed the independent prognostic value of HER2-E subtype (Table). HER2-E subtype added significant prognostic value on top of clinicopathological variables (Likelihood ratio test p < 0.001). Conclusions: HER2-E intrinsic subtype is an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of PAM50 subtype in prognostic algorithms can help refine risk stratification. These findings warrant independent validation. Clinical trial information: NCT00629278
| Univariate Cox Models for MFS | Univariate Cox Model for MFS | |||
|---|---|---|---|---|
| Factors | HR (95% CI) | p | HR (95% CI) | p |
| Stage III vs I-II | 4.33 (2.50-7.51) | < 0.001 | 4.07 (2.33-7.13) | < 0.001 |
| TILs 10% increments | 0.63 (0.43-0.91) | 0.013 | 0.55 (0.37-0.81) | 0.003 |
| Intrinsic subtype: HER2E vs other | 2.78 (1.49-5.22) | 0.001 | 3.49 (1.84-6.61) | < 0.001 |
| Hormone-receptor negative vs positive | 1.08 (0.60-1.94) | 0.804 | ||
| Grade 3 vs 1-2 | 1.97 (0.96-4.05) | 0.605 | ||
| Age: ≥60 yrs vs 18-59 yrs | 0.97 (0.55-1.72) | 0.917 | ||
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Abstract Details
Session Type
Poster Session
Session Title
Breast Cancer—Local/Regional/Adjuvant
Track
Breast Cancer
Sub Track
Adjuvant Therapy
Clinical Trial Registration Number
NCT00629278
Citation
J Clin Oncol 37, 2019 (suppl; abstr 544)
DOI
10.1200/JCO.2019.37.15_suppl.544
Abstract #
544
Poster Bd #
36
Abstract Disclosures
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