Ten-year risk of second primary malignancies among chemotherapy-treated early-stage breast cancer survivors: a multicentre cohort study from the Turkish Oncology Group

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Purpose: As survivorship improves, second primary malignancies (SPMs) have become a clinically relevant late effect of localised breast cancer treatment. Evidence from the Middle East and Balkans is scarce, and contemporary data from Türkiye are lacking. Materials and methods: We conducted a rigorous retrospective, multicentre cohort study within the Turkish Oncology Group across 14 tertiary centres. The medical records of 6, 552 women with early-stage breast cancer (2008-2022) were meticulously reviewed. SPMs were defined according to IARC/SEER multiple-primary rules, and only the first SPM per patient was included. We calculated standardised incidence ratios (SIRs) with exact Poisson 95% confidence intervals (CIs) using age- and period-specific national female incidence rates averaged over the 2010-2020 period. Person-years were stratified by attained age and calendar period to ensure the accuracy and reliability of our results. Results: During a median follow-up of 5.4 years (interquartile range, 1.1-9.4), 174 women developed pathologically confirmed SPMs. Breast cancer survivors had a significantly higher SPM risk compared to the general population (SIR, 1.66; 95% CI, 1.42-1.93). Excluding breast primaries, the excess remained (SIR 1.78; 95% CI, 1.51-2.09). The most significant increases were observed for thyroid cancer (SIR 7.09; 95% CI, 4.45-10.70) and sarcomas (SIR 7.14; 95% CI, 3.43-13.10), followed by ovarian (SIR 4.35; 95% CI, 2.58-6.89) and pancreatic cancers (SIR 4.08; 95% CI, 1.11-10.50). Risks for colorectal, brain, bladder, kidney, gastric, and contralateral breast cancers did not differ from expectations (all p>0.05). Conclusion: Turkish breast cancer survivors face a markedly increased SPM risk, especially for thyroid, sarcoma, and ovarian cancers. These findings should be interpreted cautiously in the context of treatment selection, surveillance intensity, hereditary predisposition, and regional background cancer risks. Prospective population-based studies incorporating detailed treatment exposures, germline testing, and standardized follow-up data are needed to clarify the mechanisms underlying these associations.

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