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The effect of trastuzumab-based chemotherapy in small node-negative HER2-positive breast cancer

  • Epidemiology
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An Erratum to this article was published on 17 August 2016

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.

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Abbreviations

BCSS:

Breast cancer-specific survival

CI:

Confidence interval

DFS:

Disease-free survival

DRFS:

Distant recurrence-free-survival

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

HR:

Hormone receptor

IQR:

Interquartile range

ITCs:

Isolated tumor cells

NCR:

Netherlands Cancer Registry

OS:

Overall survival

PR:

Progesterone receptor

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Acknowledgments

The authors thank the Comprehensive Cancer Centre Netherlands for the collection of data in the Netherlands Cancer Registry. In particular, we would like to thank Sabine Siesling, Annemarie Eeltink-Conijn, and Reini Bretveld for their assistance in gathering the clinical data. Furthermore, we thank Statistics Netherlands for the provision of the disease-specific survival data. Lastly, we thank Katarzyna Jozwiak and Erik van Werkhoven of the Netherlands Cancer Institute for their support with the statistical analyses.

Authors’ contributions

Study concept and design: GS. Collection and assembly of data: GS, MvdH, MvR. Data analysis and interpretation: GD, GS, MvdH, MvR, SL. Manuscript writing: GS, MvR. Critical revision of the manuscript for important intellectual content: GD, GS, MvdH, MvR, SL. Final approval of manuscript: GD, GS, MvdH, MvR, SL.

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Authors and Affiliations

  1. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands

    Mette S. van Ramshorst, Gwen M. H. E. Dackus, Sabine C. Linn & Gabe S. Sonke

  2. Netherlands Comprehensive Cancer Organisation, Godebaldkwartier 419, 3511DT, Utrecht, The Netherlands

    Margriet van der Heiden-van der Loo

  3. Department of Molecular Pathology, Utrecht University Medical Center, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands

    Gwen M. H. E. Dackus & Sabine C. Linn

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  1. Mette S. van Ramshorst
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Correspondence to Gabe S. Sonke.

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The authors declare that they have no competing interests. Relevant financial activities outside the submitted work and other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing: GS received institutional research support funding from Roche. SL is an advisory board member for Cergentis, Novartis, Roche, and Philips health BV. SL received institutional research support funding from AstraZeneca, Genentech, and Roche.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10549-016-3941-6.

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van Ramshorst, M.S., van der Heiden-van der Loo, M., Dackus, G.M.H.E. et al. The effect of trastuzumab-based chemotherapy in small node-negative HER2-positive breast cancer. Breast Cancer Res Treat 158, 361–371 (2016). https://doi.org/10.1007/s10549-016-3878-9

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