Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial

Author(s): PierFranco Conte, MD, PhD1,2; Giancarlo Bisagni, MD3; Federico Piacentini, MD, PhD4; Samanta Sarti, MD, PhD5; Santino Minichillo, MD6; Elisa Anselmi, MD7; Michele Aieta, MD8; Vittorio Gebbia, MD9; Alessio Schirone, MD10; Antonino Musolino, MD, PhD11; Ornella Garrone, MD, PhD12; Alessandra Beano, MD13; Anita Rimanti, MD14; Francesco Giotta, MD15; Anna Turletti, MD16; Federica Miglietta, MD17,18; Maria Vittoria Dieci, MD17,18; Roberto Vicini, PhD19; Sara Balduzzi, MD20; Robert D’Amico, PhD4; and Valentina Guarneri, MD, PhD17,18
Source: DOI: 10.1200/JCO.23.00790 Journal of Clinical Oncology 41, no. 32 (November 10, 2023) 4976-4981.
Original Article
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This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer.  With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.
We present the final analysis of the phase III noninferiority, randomized ShortHER trial comparing 9 weeks versus 1 year of adjuvant trastuzumab with chemotherapy in patients with human epidermal growth factor receptor 2–positive (HER2+) early breast cancer (BC). Women with HER2+ BC were randomly assigned to anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or 9-week trastuzumab (arm B, short). Here, we report the second coprimary end point overall survival (OS), updated disease-free survival (DFS), and outcomes according to hormone receptor status, age, and nodal status. At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively. Ten-year OS is 89% versus 88% in the long versus short arm, respectively. 10-year DFS rates in the long versus short arm according to nodal status are N0 81% versus 85%; N1-3 77% versus 79%; and N4+ 63% versus 53%. Ten-year OS rates in long versus short arm according to nodal status are N0 89% versus 95%%; N1-3 92% versus 89%; and N4+ 84% versus 64%. The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2+ early BC as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1-3) is negligible, while patients with N4+ have a clear benefit with 1-year trastuzumab.

Author Affiliations

1S Camillo Hospital, IRCCS, Venezia, Italy; 2University of Padova, Padova, Italy; 3Department of Oncology and Advanced Technologies, Azienda USL-IRCCS, Reggio Emilia, Italy; 4Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, Modena, Italy; 5IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” IRST srl, Meldola, Italy; 6Medical Oncology, Bellaria Hospital, Bologna, Italy; 7Department of Oncology and Hematology, ASL Piacenza, Piacenza, Italy; 8Medical Oncology, IRCCS-CROB, Rionero in Vulture, Italy; 9Kore University, Enna and La Maddalena Clinic, Palermo, Italy; 10S Anna University Hospital, Ferrara, Italy; 11University Hospital, Parma, Italy; 12IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; 13Breast Oncology, Città della Salute e della Scienza, Torino, Italy; 14Carlo Poma Hospital, ASST Mantova, Mantova, Italy; 15IRCCS Istituto Oncologico Giovanni Paolo II, Bari, Italy; 16Senology, Ospedale Martini, ASL Città di Torino, Torino, Italy; 17Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; 18Oncology 2, Veneto Oncology Institute, IOV-IRCCS, Padova, Italy; 19Statistical Unit, University Hospital, Modena, Italy; 20University of Modena and Reggio Emilia, Modena, Italy

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