Long-term prognostic role of functional limitations among women with breast cancer

Abstract

Background: The long-term prognostic role of functional limitations among women with breast cancer is poorly understood.

Methods: We studied a cohort of 2202 women with breast cancer at two sites in the United States, who provided complete information on body functions involving endurance, strength, muscular range of motion, and small muscle dexterity following initial adjuvant treatment. Associations of baseline functional limitations with survival were evaluated in delayed entry Cox proportional hazards models, with adjustment for baseline sociodemographic factors, body mass index, smoking, physical activity, comorbidity, tumor characteristics, and treatment. Difference in covariates between women with and without limitations was assessed with Pearson χ(2) and Student t tests. All statistical tests were two-sided.

Results: During the median follow-up of 9 years, 112 deaths were attributable to competing causes (5% of the cohort) and 157 were attributable to breast cancer causes (7% of the cohort). At least one functional limitation was present in 39% of study participants. Proportionately, more breast cancer patients with functional limitations after initial adjuvant treatment were older, less educated, and obese (P < .001). In multivariable models, functional limitations were associated with a statistically significantly increased risk of death from all causes (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03 to 1.92) and from competing causes (HR = 2.60, 95% CI = 1.69 to 3.98) but not from breast cancer (HR = 0.90, 95% CI = 0.64 to 1.26). The relationship between functional limitations and overall survival differed by tumor stage (among women with stage I and stage III breast cancer, HR = 2.02, 95% CI = 1.23 to 3.32 and HR = 0.74, 95% CI = 0.42 to 1.30, respectively).

Conclusion: In this prospective cohort study, functional limitations following initial breast cancer treatment were associated with an important reduction in all-cause and competing-cause survival, irrespective of clinical, lifestyle, and sociodemographic factors.

Figure 1

Flow diagram of participants in the cohort study.

Figure 2

Kaplan–Meier survival curves according to functional limitations. A) Overall survival for breast cancer patients with and without functional limitations. B) Competing-cause (non-breast cancer) survival for women with and without functional limitations. C) Breast cancer–specific survival for women with and without functional limitations. In each graph, the solid line indicates the proportion of breast cancer patients surviving without functional limitations and the dotted line indicates the proportion of breast cancer patients surviving with functional limitations. At 0, 5, and 10 years after breast cancer diagnosis, the numbers of patients at risk of death from all causes are shown. Plots were computed with baseline data on functional limitations obtained following initial adjuvant treatment. Hazard ratios and 95% confidence intervals are given in Table 2.