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Risk of New Primary Nonbreast Cancers After Breast Cancer Treatment: A Dutch Population-Based Study

Michael Schaapveld, Otto Visser, Marieke J. Louwman, Elisabeth G.E. de Vries, Pax H.B. Willemse, Renée Otter, Winette T.A. van der Graaf, Jan-Willem W. Coebergh, Flora E. van Leeuwen

From the Comprehensive Cancer Center North-Netherlands; Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen; Comprehensive Cancer Center; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam; Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen; Comprehensive Cancer Center South, Eindhoven; and the Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands

Corresponding author: Michael Schaapveld, PhD, Comprehensive Cancer Center North-Netherlands (CCCN), P.O. Box 330, 9700 AH Groningen, The Netherlands; e-mail: m.schaapveld{at}ikn.nl

Purpose: To assess the risk of secondary nonbreast cancers (SNBCs) in a recently treated population-based cohort of breast cancer patients focused on the association with treatment and prognostic implications.

Patients and Methods: In 58,068 Dutch patients diagnosed with invasive breast cancer between 1989 and 2003, SNBC risk was quantified using standardized incidence ratios (SIRs), cumulative incidence, and Cox regression analysis, adjusted for competing risks.

Results: After a median follow-up of 5.4 years, 2,578 SNBCs had occurred. Compared with the Dutch female population at large, in this cohort, the SIR of SNBCs was increased (SIR, 1.22; 95% CI, 1.17 to 1.27). The absolute excess risk was 13.6 (95% CI, 9.7 to 17.6) per 10,000 person-years. SIRs were elevated for cancers of the esophagus, stomach, colon, rectum, lung, uterus, ovary, kidney, and bladder cancers, and for soft tissue sarcomas (STS), melanoma, non-Hodgkin's lymphoma, and acute myeloid leukemia (AML). The 10-year cumulative incidence of SNBCs was 5.4% (95% CI, 5.1% to 5.7%). Among patients younger than 50 years, radiotherapy was associated with an increased lung cancer risk (hazard ratio [HR] = 2.31; 95% CI, 1.15 to 4.60) and chemotherapy with decreased risk for all SNBCs (HR = 0.78; 95% CI, 0.63 to 0.98) and for colon and lung cancer. Among patients age 50 years and older, radiotherapy was associated with raised STS risk (HR = 3.43; 95% CI, 1.46 to 8.04); chemotherapy with increased risks of melanoma, uterine cancer, and AML; and hormonal therapy with all SNBCs combined (HR = 1.10; 95% CI, 1.01 to 1.21) and uterine cancer (HR = 1.78; 95% CI, 1.40 to 2.27). An SNBC worsened survival (HR = 3.98; 95%CI 3.77 to 4.20).

Conclusion: Breast cancer patients diagnosed in the 1990s experienced a small but significant excess risk of developing an SNBC.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.