In a Danish Breast Cancer Group nationwide prospective cohort study reported in The Lancet Oncology, Jensen et al attempted to develop a prognostic standard mortality rate index to predict excess mortality based on risk-adapted adjuvant therapy in postmenopausal patients with early-stage breast cancer.
Study Details
The study included postmenopausal women (aged 50 or older) with invasive estrogen receptor–positive, HER2-negative, resected breast cancer registered in the Danish Breast Cancer Group clinical database. Factors in prognostic standard mortality rate index (PSI) calculation included the type of surgery, tumor size, nodal status, histologic type, malignancy grade, lymphovascular invasion, and allocation to radiotherapy or not. Patients in the PSI 1 category were recommended for 5 years of endocrine therapy; patients in the PSI categories 2, 3, or 4 were recommended for endocrine therapy plus adjuvant chemotherapy, according to Danish national guidelines. The primary endpoint was standard mortality ratio.
Key Findings
Among 25,027 women diagnosed with breast cancer between August 2013 and December 2018 and registered with the Danish Breast Cancer Group database, 8,921 were eligible for the study. They were assigned a PSI category: PSI 1 = 6,704 (75%); PSI 2 = 1,300 (15%); PSI 3 = 745 (8%); and PSI 4 = 172 (2%). In total, 8,514 of 8,830 women (96%) started endocrine therapy, with 91 having an unknown therapy status.
Adherence to endocrine therapy at 4.5 years was 67.8% (95% confidence interval [CI] = 66.6%–69.0%) in the PSI 1 group and 72.3% (95% CI =70.5%–74.3%) in the PSI 2, 3, and 4 groups.
Crude standard mortality ratios were 0.89 (95% CI = 0.85–0.95) in the PSI 1 group, 1.71 (95% CI = 1.47–1.97) in the PSI 2 group, and 2.39 (95% CI = 1.99–2.88) in the PSI 3 and 4 groups. Compared with patients in the PSI 1 group who completed endocrine therapy, relative risks for excess mortality were 1.33 (95% CI = 1.01–1.76) for patients in the PSI 2 group who completed adjuvant endocrine therapy and chemotherapy and 2.31 (95% CI = 1.74–3.05) for patients in the PSI 3 or 4 group who completed adjuvant therapy. The relative risk among patients in the PSI 3 or 4 group who did not complete adjuvant therapy was 4.89 (95% CI = 3.74–6.39).
The investigators concluded: “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[ly] 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.”
Maj-Britt Jensen, MSc, of the Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, is the corresponding author of The Lancet Oncology article.
Disclosure: The investigators reported there was no external funding for the study. For full disclosures of all study authors, visit The Lancet Oncology.
