Symptoms of endocrine treatment and outcome in the BIG 1-98 study

Abstract

There may be a relationship between the incidence of vasomotor and arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast cancer patients with endocrine-responsive disease who received adjuvant letrozole or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1-98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal tunnel (AMC) symptoms reported at baseline, started protocol treatment and were alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month landmark (n = 4,682) were used for this report. Cohorts of patients with vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12 months from randomization. Landmark analyses were performed for disease-free survival (DFS) and for breast cancer free interval (BCFI), using regression analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month landmark, HR (95 % CI) for DFS = 0.65 (0.49-0.87), and for BCFI = 0.70 (0.49-0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70-0.96)] and BCFI (12-month DFS HR (95 % CI) = 0.97 (0.80-1.18). Interaction tests indicated no effect of treatment group on associations between symptoms and outcomes. While reporting of AMC symptoms was clearly associated with better DFS and BCFI, the association between vasomotor symptoms and outcome was less clear, especially with respect to breast cancer-related events.

Trial registration: ClinicalTrials.gov NCT00004205.

Conflict of interest statement

Author Conflicts

None: Jens Huober, Bernard F. Cole, Manuela Rabaglio, Anita Giobbie-Hurder, Jimin Wu, Karen N. Price, Alan S. Coates, Richard D. Gelber, Hervé Bonnefoi, István Láng, Ian Smith, Marco Colleoni, Aron Goldhirsch, Patrick Neven

Novartis advisory board, Novartis research support: Bent Ejlertsen

Novartis honoraria: Andrew Wardley, John F. Forbes

Astra Zeneca honoraria, Genomic health consultancy/advisory: John F. Forbes

Novartis stock: Beat Thürlimann

Figures

Figure 1

CONSORT diagram showing the patient population for this analysis.

Figure 2

Cumulative incidence according to occurrence of adverse events within 3 months (A,C) and within 12 months (B,D) of randomization for disease-free survival (DFS) (A, B) and breast-cancer-free interval (BCFI) (C,D). Non-breast cancer events are considered as competing risks. (AMC: arthralgia, myalgia, carpal tunnel syndrome)

Figure 3

Multivariable analysis results according to occurrence of adverse events within 3 months (A,C) and within 12 months (B,D) of randomization for disease-free survival (DFS) based on proportional hazards regression (A, B) and breast-cancer-free interval (BCFI) based on competing-risks regression(C,D). Figure 3 footnote. Hazard ratios are based on a multivariable model including all variables listed as well as cooperative trial group. Proportional hazards regression of DFS was stratified by randomization option (2-arm vs. 4-arm) and chemotherapy use. For each variable included, a hazard ratio less than 1.0 indicates lower hazard than the referent group, and a hazard ratio greater than 1.0 indicates higher hazard than the referent group.

Figure 3

Multivariable analysis results according to occurrence of adverse events within 3 months (A,C) and within 12 months (B,D) of randomization for disease-free survival (DFS) based on proportional hazards regression (A, B) and breast-cancer-free interval (BCFI) based on competing-risks regression(C,D). Figure 3 footnote. Hazard ratios are based on a multivariable model including all variables listed as well as cooperative trial group. Proportional hazards regression of DFS was stratified by randomization option (2-arm vs. 4-arm) and chemotherapy use. For each variable included, a hazard ratio less than 1.0 indicates lower hazard than the referent group, and a hazard ratio greater than 1.0 indicates higher hazard than the referent group.

Figure 3

Multivariable analysis results according to occurrence of adverse events within 3 months (A,C) and within 12 months (B,D) of randomization for disease-free survival (DFS) based on proportional hazards regression (A, B) and breast-cancer-free interval (BCFI) based on competing-risks regression(C,D). Figure 3 footnote. Hazard ratios are based on a multivariable model including all variables listed as well as cooperative trial group. Proportional hazards regression of DFS was stratified by randomization option (2-arm vs. 4-arm) and chemotherapy use. For each variable included, a hazard ratio less than 1.0 indicates lower hazard than the referent group, and a hazard ratio greater than 1.0 indicates higher hazard than the referent group.

Figure 3

Multivariable analysis results according to occurrence of adverse events within 3 months (A,C) and within 12 months (B,D) of randomization for disease-free survival (DFS) based on proportional hazards regression (A, B) and breast-cancer-free interval (BCFI) based on competing-risks regression(C,D). Figure 3 footnote. Hazard ratios are based on a multivariable model including all variables listed as well as cooperative trial group. Proportional hazards regression of DFS was stratified by randomization option (2-arm vs. 4-arm) and chemotherapy use. For each variable included, a hazard ratio less than 1.0 indicates lower hazard than the referent group, and a hazard ratio greater than 1.0 indicates higher hazard than the referent group.