Matteo Lambertini1,2, Christine Campbell3, Richard D Gelber4, Giuseppe Viale5, Ann McCullough6, Florentine Hilbers7, Larissa A Korde8, Olena Werner9, Saranya Chumsri10, Christian Jackisch11, Antonio C Wolff12, Ines Vaz-Luis13, Arlindo R Ferreira14, Aleix Prat15, Alvaro Moreno-Aspitia10, Martine Piccart16, Sherene Loi17, Evandro de Azambuja16. 1. Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genova, Italy. matteo.lambertini@unige.it. 2. Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy. matteo.lambertini@unige.it. 3. Frontier Science, Kingussie, UK. 4. Dana-Farber Cancer Institute, Harvard Medical School, Harvard TH Chan School of Public Health and Frontier Science and Technology Research Foundation, Boston, MA, USA. 5. IEO, European Institute of Oncology IRCCS, University of Milan, Milan, Italy. 6. Mayo Clinic, Phoenix, AZ, USA. 7. Breast International Group, Brussels, Belgium. 8. National Cancer Institute, Bethesda, MD, USA. 9. Novartis Pharma AG, Basel, Switzerland. 10. Mayo Clinic, Jacksonville, FL, USA. 11. Sana Klinikum Offenbach, Offenbach, Germany. 12. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. 13. Institut Gustave Roussy, Villejuif, France. 14. Champalimaud Clinical Center, Champalimaud Foundation and Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. 15. Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain. 16. Institut Jules Bordet and Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. 17. Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia.
Abstract
PURPOSE: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receivingadjuvant anti-HER2 therapy. METHODS: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0-5 and 6-8. RESULTS: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0-5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6-8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6-8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0-5, and 6-8 were different in patients with HR-positive and HR-negative tumors. CONCLUSIONS: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.
RCT Entities:
PURPOSE: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancerpatients receiving adjuvant anti-HER2 therapy. METHODS: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancerpatients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0-5 and 6-8. RESULTS: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0-5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6-8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6-8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0-5, and 6-8 were different in patients with HR-positive and HR-negative tumors. CONCLUSIONS:HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.
Entities:
Keywords:
Breast cancer; Estrogen receptor; HER2; Progesterone receptor
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