New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole – Analyses from NCIC CTG MA.17

• Published in: Breast (Edinburgh) 2016-06, Vol.27, p.99-104
• Main Authors: Liedke, P.E.R, Tu, D, Shepherd, L, Chavarri-Guerra, Y, Pritchard, K.I, Stearns, V, Goss, P.E
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - administration & dosage; Aromatase inhibitors; Autonomic Nervous System Diseases - etiology; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Chemotherapy, Adjuvant; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Extended hormonal therapy; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; Letrozole; Middle Aged; Multivariate Analysis; Musculoskeletal Diseases - etiology; Musculoskeletal symptoms; Nitriles - administration & dosage; Proportional Hazards Models; Tamoxifen - administration & dosage; Time Factors; Treatment Outcome; Triazoles - administration & dosage; Vasomotor symptoms; Vasomotor System - physiopathology
• ISSN: 0960-9776; 1532-3080
• DOI: 10.1016/j.breast.2016.02.010

Abstract Purpose New onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen. Methods Symptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without. Results Data post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28–0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24–0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24–0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22–0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint. Conclusions New onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.