TY - JOUR
T1 - Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer
T2 - exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial
AU - Lambertini, Matteo
AU - Campbell, Christine
AU - Gelber, Richard D.
AU - Viale, Giuseppe
AU - McCullough, Ann
AU - Hilbers, Florentine
AU - Korde, Larissa A.
AU - Werner, Olena
AU - Chumsri, Saranya
AU - Jackisch, Christian
AU - Wolff, Antonio C.
AU - Vaz-Luis, Ines
AU - Ferreira, Arlindo R.
AU - Prat, Aleix
AU - Moreno-Aspitia, Alvaro
AU - Piccart, Martine
AU - Loi, Sherene
AU - de Azambuja, Evandro
N1 - Funding Information:
Dr. Lambertini received honoraria from Teva and speaker’s bureau from Theramex outside the submitted work. Dr. Gelber received research grants from Novartis Pharma AG, Pfizer, Roche-Genentech, Ipsen, Celgene, Merck, and Ferring (to the institution). Dr. Werner reports employment at Novartis Pharma AG. Dr. Vaz-Luis received honoraria from Novartis Pharma AG, AstraZeneca, and Ipsen/Kephren outside the submitted work, and research grants from Susan Komen for Cure and Odyssea. Dr. Piccart is a board member of Radius, received honoraria from AstraZeneca, Lilly, MSD, Novartis Pharma AG, Odonate, Pfizer, Roche-Genentech, Camel-IDS, Crescendo Biologics, Periphagen, Huya, Debiopharm, PharmaMar, G1 Therapeutics, Menarini, Seattle Genetics, Immunomedics, Oncolytics outside the submitted work, and research grants from AstraZeneca, Lilly, MSD, Novartis Pharma AG, Pfizer, Roche-Genentech, Synthon, Radius, Servier (to the institution). Dr. Loi acted as consultant (not compensated) to Seattle Genetics, Pfizer, Novartis Pharma AG, BMS, Merck, and Roche-Genentech outside the submitted work, and received research grants from Novartis Pharma AG, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology, and Pfizer (to the institution). Dr. de Azambuja received honoraria from Roche-Genentech, research grants from Roche–Genentech (to the institution), and travel grants from Roche-Genentech and GlaxoSmithKline outside the submitted work. All the other authors declare no competing interests.
Funding Information:
The ALTTO trial received financial support from GlaxoSmithKline (until January 2015), Novartis Pharma AG (as of January 2015), and the National Cancer Institute of the National Institutes of Health (NCI-NIH; Grant No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology and Grant No. CA025224 to the legacy North Central Cancer Treatment Group). The present analysis did not receive additional funding. The funders and sponsors had no role in the design or conduct of the study, in the collection, analysis, or interpretation of the data, neither in the preparation, review, or approval of the manuscript.
Funding Information:
Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium) during the conduction of this analysis. We also acknowledge the ALTTO staff of the BrEAST Data Centre at Institut Jules Bordet in Brussels (Belgium), for clinical record online management, and Sebastien Guillaume of BrEAST Data Centre at Institut Jules Bordet in Brussels (Belgium) for administrative support. None of the individuals named in the acknowledgment received any compensation for their contributions.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/8/30
Y1 - 2019/8/30
N2 - Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients 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 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.
AB - Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients 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 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.
KW - Breast cancer
KW - Estrogen receptor
KW - HER2
KW - Progesterone receptor
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UR - http://www.scopus.com/inward/citedby.url?scp=85069158221&partnerID=8YFLogxK
U2 - 10.1007/s10549-019-05284-y
DO - 10.1007/s10549-019-05284-y
M3 - Article
C2 - 31134488
AN - SCOPUS:85069158221
VL - 177
SP - 103
EP - 114
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 1
ER -