The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: A population based study in the Netherlands

Background: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. Results: Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4-2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6-14.8) when <35 to 1.5 (95% CI 1.4-1.7) for ≥60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48-0.69) and chemotherapy (HR 0.73; 95% CI 0.60-0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33-1.56). Conclusion: Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection.

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