Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors

Emma Zattarin; Daniele Presti; Luigi Mariani; Caterina Sposetti; Rita Leporati; Alice Menichetti; Chiara Corti; Chiara Benvenuti; Giovanni Fucà; Riccardo Lobefaro; Francesca Ligorio; Leonardo Provenzano; Andrea Vingiani; Marta Del Vecchio; Gaia Griguolo; Marianna Sirico; Ottavia Bernocchi; Antonio Marra; Paola Zagami; Elisa Agostinetto; Flavia Jacobs; Pierluigi Di Mauro; Andrea Esposito; Carlo Alberto Giorgi; Luca Lalli; Laura Boldrini; Pier Paolo Berton Giacchetti; Ambra Carnevale Schianca; Valentina Guarneri; Rebecca Pedersini; Agnese Losurdo; Alberto Zambelli; Daniele Generali; Carmen Criscitiello; Giuseppe Curigliano; Giancarlo Pruneri; Filippo de Braud; Maria Vittoria Dieci; Claudio Vernieri

doi:10.1038/s41523-023-00534-1

Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors

NPJ Breast Cancer. 2023 Apr 17;9(1):27. doi: 10.1038/s41523-023-00534-1.

Authors

Emma Zattarin^#¹, Daniele Presti^#¹, Luigi Mariani², Caterina Sposetti¹, Rita Leporati¹, Alice Menichetti³, Chiara Corti⁴, Chiara Benvenuti^{5

6}, Giovanni Fucà¹, Riccardo Lobefaro¹, Francesca Ligorio^{1

7}, Leonardo Provenzano¹, Andrea Vingiani^{8

9}, Marta Del Vecchio¹⁰, Gaia Griguolo^{3

11}, Marianna Sirico¹², Ottavia Bernocchi¹³, Antonio Marra^{4

14}, Paola Zagami⁴, Elisa Agostinetto^{5

6

15}, Flavia Jacobs^{5

6}, Pierluigi Di Mauro¹⁶, Andrea Esposito¹⁶, Carlo Alberto Giorgi³, Luca Lalli², Laura Boldrini⁴, Pier Paolo Berton Giacchetti⁴, Ambra Carnevale Schianca⁴, Valentina Guarneri^{3

11}, Rebecca Pedersini¹⁶, Agnese Losurdo^{5

6}, Alberto Zambelli^{5

6}, Daniele Generali^{17

18}, Carmen Criscitiello^{4

9}, Giuseppe Curigliano^{4

9}, Giancarlo Pruneri^{8

9}, Filippo de Braud^{1

9}, Maria Vittoria Dieci^{3

11}, Claudio Vernieri^{19

20}

Affiliations

¹ Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
² Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
³ Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
⁴ Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.
⁵ IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy.
⁶ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy.
⁷ IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.
⁸ Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁹ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
¹⁰ Division of Pharmacy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.
¹¹ Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy.
¹² Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014, Meldola, Italy.
¹³ Farmacia Ospedaliera ASST Cremona, Viale Concordia 1, Cremona, Italy.
¹⁴ Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
¹⁵ Institut Jules Bordet and l'Université Libre de Bruxelles, Bruxelles, Belgium.
¹⁶ Medical Oncology Unit, ASST Spedali Civili, Brescia, Italy.
¹⁷ Breast Cancer Unit & Translational Research Unit, ASST Cremona, Cremona, Italy.
¹⁸ Department of Medical, Surgery and Health Sciences, University of Trieste, 34147, Trieste, Italy.
¹⁹ Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. claudio.vernieri@istitutotumori.mi.it.
²⁰ IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy. claudio.vernieri@istitutotumori.mi.it.

^# Contributed equally.

Abstract

Whether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting.

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States