The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype

Iris Kramer, Michael Schaapveld, Hester S.A. Oldenburg, Gabe S. Sonke, Danielle McCool, Flora E. van Leeuwen, Koen K. van de Vijver, Nicola S. Russell, Sabine C. Linn, Sabine Siesling, C. Willemien Menke-van der Houven van Oordt, Marjanka K. Schmidt

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Abstract

Background
An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC.

Methods
This population-based cohort study included female patients diagnosed with first invasive BC between 2003-2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry, and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC, and CBC-subtypes.

Results
Of 83,144 BC patients, 2,816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI]=3.7-4.0%). Overall, adjuvant chemotherapy: HR = 0.70; 95%CI=0.62-0.80, endocrine therapy: HR = 0.46; 95%CI=0.41-0.52, and trastuzumab with chemotherapy: HR = 0.57; 95%CI=0.45-0.73 were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48; 95%CI=0.36-0.62) and aromatase inhibitors (HR = 0.32; 95%CI=0.23-0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of ER-positive CBC (HR = 0.41; 95%CI=0.36-0.47), but not ER-negative CBC (HR = 1.32, 95%CI=0.90-1.93), compared to no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84; 95%CI=1.62-4.99), compared to patients not receiving chemotherapy for ER-negative first BC.

Conclusion
Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduces CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC-subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction.
Original languageEnglish
Article numberdjz010
Pages (from-to)709-718
Number of pages10
JournalJournal of the National Cancer Institute
Volume111
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

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    Kramer, I., Schaapveld, M., Oldenburg, H. S. A., Sonke, G. S., McCool, D., van Leeuwen, F. E., ... Schmidt, M. K. (2019). The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype. Journal of the National Cancer Institute, 111(7), 709-718. [djz010]. https://doi.org/10.1093/jnci/djz010