title: The effect of trastuzumab-based chemotherapy in small node-negative HER2-positive breast cancer.
abstract: The prognosis of patients with stage II-III Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer has significantly improved since the addition of trastuzumab to (neo-)adjuvant chemotherapy. Several reports have shown that small (≤2 cm), node-negative, HER2-positive tumors have a relatively poor prognosis and these patients increasingly receive trastuzumab-based chemotherapy. We aimed to provide evidence for this approach in a population-based cohort. All T1N0M0 HER2-positive breast cancer patients diagnosed between 2006 and 2012 were identified from the Netherlands Cancer Registry. Patient, tumor, and treatment characteristics were recorded. Kaplan-Meier statistics were used for overall survival (OS) and breast cancer-specific survival (BCSS) estimations overall and in T1a, T1b, and T1c tumors separately. Cox regression analyses were performed to account for imbalances in baseline characteristics between treated and untreated patients. A total of 3512 patients were identified: 385 with T1a, 800 with T1b, and 2327 with T1c tumors. Forty-five percent of patients received chemotherapy and/or trastuzumab: 92 % received both. Chemotherapy and/or trastuzumab significantly improved 8-year OS (95 vs. 84 %; hazard ratio [HR] 0.29; 95 % confidence interval [CI] 0.21-0.41, P < 0.001). The effect remained significant in multivariable analyses (HR 0.35; 95 % CI 0.23-0.52, P < 0.001). BCSS was also improved with systemic treatment in univariable (96 vs. 92 %; HR 0.41; 95 % CI 0.27-0.63, P < 0.001) and multivariable analyses (HR 0.31; 95 % CI 0.19-0.53, P < 0.001). Treatment effect on OS and BCSS was similar in T1a, T1b, and T1c tumors. Chemotherapy and/or trastuzumab improves OS and BCSS and can be considered in all patients with small node-negative HER2-positive breast cancer.
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
authors.forename: Mette S
authors.initials: MS
authors.lastname: van Ramshorst
authors.affiliation: Netherlands Comprehensive Cancer Organisation, Godebaldkwartier 419, 3511DT, Utrecht, The Netherlands.
authors.forename: Margriet
authors.initials: M
authors.lastname: van der Heiden-van der Loo
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.|Department of Molecular Pathology, Utrecht University Medical Center, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: Gwen M H E
authors.initials: GM
authors.lastname: Dackus
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.|Department of Molecular Pathology, Utrecht University Medical Center, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Linn
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands. g.sonke@nki.nl.
authors.forename: Gabe S
authors.initials: GS
authors.lastname: Sonke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004358:Drug Therapy; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009426:Netherlands; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012042:Registries; D016019:Survival Analysis; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; Overall survival; Systemic treatment; Trastuzumab