Outcomes based on risk-adapted adjuvant therapy in postmenopausal women with early breast cancer: a nationwide, prospective cohort study by the Danish Breast Cancer Group

Abstract

Background: Clinical prediction models are increasingly used to guide treatment in patients with early breast cancer. The Danish Breast Cancer Group (DBCG) has developed a prognostic standard mortality rate index (PSI) for prediction of excess mortality based on 5 years of endocrine therapy. In this study, we aimed to evaluate the clinical utility of the PSI.

Methods: In this nationwide, prospective cohort study, we included postmenopausal Danish women aged 50 years or older with invasive oestrogen receptor-positive and HER2-negative resected breast cancer registered in the DBCG clinical database (close to all Danish women newly diagnosed with invasive breast cancer are registered in the national database). All participants were assigned a PSI category. Patients in the PSI 1 category were recommended 5 years of endocrine therapy; patients in PSI 2, 3, or 4 category were recommended endocrine therapy plus adjuvant chemotherapy according to Danish national guidelines. The primary endpoint was standard mortality ratio. Univariable and multivariable analyses for standard mortality ratio, overall survival, and recurrence-free survival were performed applying Kaplan-Meier, cumulative incidence, Poisson regression, and Fine-Gray subdistribution hazards model.

Findings: 25 027 women diagnosed with breast cancer between Aug 1, 2013, and Dec 31, 2018, and registered with the DBCG clinical database were identified. 8921 of those registered were eligible, assigned a PSI category (6704 [75%] PSI 1, 1300 [15%] PSI 2, 745 [8%] PSI 3, and 172 [2%] PSI 4), and included in the study. 8514 [96%] of 8830 women initiated endocrine therapy and 91 had an unknown therapy status. Adherence at 4·5 years was 67·8% (66·6-69·0) in the PSI 1 group and 72·3% (70·5-74·3) in the PSI 2-4 groups. Crude standard mortality ratio was 0·89 (95% CI 0·85-0·95) with PSI 1, 1·71 (95% CI 1·47-1·97) with PSI 2, and 2·39 (95% CI 1·99-2·88) with PSI 3-4. Compared with patients who completed adjuvant therapy with PSI 1, relative risk (RR) for excess mortality was 1·33 (95% CI 1·01-1·76) for patients with PSI 2 whereas patients with PSI 3-4 retained an excess mortality (RR 2·31, 95% CI 1·74-3·05) even with completed therapy.

Interpretation: These data validate the clinical use of the PSI tool for risk adapted treatment allocation. In patients with PSI 1, the omission of chemotherapy was not associated with excess mortality overall and a distinct better outcome was seen in patients with completed endocrine therapy versus those who had not completed. With completed adjuvant therapy, excess mortality was low for patients with PSI 2, whereas patients with PSI 3-4 had high excess mortality, potentially warranting intensified treatment and requiring further investigation.

Funding: None.