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J Natl Cancer Inst. 2019 Jan 30. doi: 10.1093/jnci/djz010. [Epub ahead of print]

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

Author information

1
Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
2
Division of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
3
Department of Surgical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
4
Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
5
Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
6
Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
7
Department of Pathology, University Medical Centre Utrecht, Utrecht, the Netherlands.
8
Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands.
9
Department of Health Technology and Service Research, Technical Medical Center, University of Twente, Enschede, the Netherlands.
10
Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.

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.

PMID:
30698719
DOI:
10.1093/jnci/djz010

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