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Lymphatic System and Diseases / Cancer Risks and Factors / Breast Cancer Treatment Studies · Journal article
Biomolecules and Biomedicine · August 18, 2026
Reinforces what was already believed, rather than introducing something new.
This large retrospective cohort study of 74,233 women with stage II–III breast cancer found no clinically meaningful or statistically significant difference in long-term circulatory mortality between those receiving preoperative versus postoperative chemotherapy. The findings support a broader, multimorbidity-focused approach to survivorship care in older long-term survivors rather than chemotherapy-sequence-driven circulatory risk stratification.
Retrospective population-based cohort study. Women aged any with stage II–III non-metastatic invasive breast cancer diagnosed between 2010 and 2015 in the SEER database who received chemotherapy and definitive surgery.. Intervention: Recorded preoperative (neoadjuvant) systemic chemotherapy followed by surgery. Compared with: Recorded postoperative (adjuvant) systemic chemotherapy following surgery. n = 74,233. SEER database (United States).
Weighted 10-year cumulative incidence of circulatory death: 2.06% after preoperative systemic therapy versus 2.10% after postoperative therapy, risk difference −0.05 percentage points (95% CI, −0.31 to 0.18) Cause-specific hazard ratio for circulatory mortality: 1.092 (95% CI, 0.968–1.231) Subdistribution hazard ratio: 1.024 (95% CI, 0.920–1.140)
Cause-specific hazard ratio for circulatory mortality: 1.092 (95% CI, 0.968–1.231) Among deaths after five-year landmark in women aged ≥75 years, circulatory mortality accounted for 25.5% but other non-circulatory causes remained largest at 49.9%
Clinicians should not base the choice between neoadjuvant and adjuvant chemotherapy on concerns about long-term circulatory mortality. In older long-term survivors, a comprehensive survivorship approach addressing multiple competing health risks is more appropriate than a chemotherapy-sequence-based cardiovascular strategy.
A large, well-designed retrospective cohort study with robust methods (inverse-probability weighting, competing-risks analysis) that confirms the absence of a clinically meaningful difference in circulatory mortality between treatment sequences, with narrow confidence intervals crossing the null.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should not base the choice between neoadjuvant and adjuvant chemotherapy on concerns about long-term circulatory mortality. In older long-term survivors, a comprehensive survivorship approach addressing multiple competing health risks is more appropriate than a chemotherapy-sequence-based cardiovascular strategy.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Most women with operable breast cancer increasingly survive long enough for non-cancer causes to become important contributors to mortality, particularly at older ages. We investigated whether the recorded sequence of systemic therapy relative to surgery among women receiving chemotherapy was associated with circulatory mortality and examined how causes of death evolve in long-term survivors. This retrospective population-based cohort study included 74,233 women with stage II–III non-metastatic invasive breast cancer diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database who received chemotherapy and definitive surgery. A six-month landmark was used to reduce immortal-time bias, and treatment groups were balanced using stabilized inverse-probability-of-treatment weighting. Weighted cumulative incidence, cause-specific hazard, and Fine–Gray subdistribution models were used to evaluate circulatory mortality, while mortality patterns after a five-year landmark were examined descriptively by age. Median follow-up was 10.8 years. The weighted 10-year cumulative incidence of circulatory death was 2.06% after recorded preoperative systemic therapy and 2.10% after postoperative therapy, corresponding to a risk difference of −0.05 percentage points (95% confidence interval [CI], −0.31 to 0.18). The cause-specific hazard ratio was 1.092 (95% CI, 0.968–1.231), and the subdistribution hazard ratio was 1.024 (95% CI, 0.920–1.140). Among deaths occurring after the five-year landmark, the circulatory share increased with age, reaching 25.5% in women aged ≥75 years at diagnosis; however, other non-circulatory causes remained the largest category (49.9%). In women aged ≥75 years who survived five years, circulatory mortality approached and eventually exceeded breast-cancer mortality, but the difference was not significant at the prespecified seven-year time point. The recorded systemic-therapy/surgery sequence was not associated with long-term circulatory mortality. In older long-term breast-cancer survivors, late mortality is predominantly multimorbid rather than circulatory-dominant, supporting survivorship care that addresses cardiovascular risk within a broader framework of age-related competing health risks.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.