Novel association of pre-chemotherapy immune cell profiles with functional decline and resilience in women with breast cancer receiving chemotherapy.

Abstract

549 Background: Chemotherapy adversely affects physical function. While many patients recover after treatment (i.e. are resilient), some are unable to return to their pre-treatment function (i.e. are non-resilient). Since immune dysfunction may play a role in functional decline, we assessed the relationship of pre-chemotherapy immune cell profiles with functional decline and resilience in women with breast cancer receiving chemotherapy. Methods: This study was based on a large nationwide cohort study in women with stage I-III breast cancer. Physical function was measured by the Functional Assessment of Cancer Therapy: General – Physical subscale (FACT-PWB) ≤7 days before chemotherapy (T1), ≤1 month after chemotherapy (T2), and 6 months after T2 (T3). Functional decline at T2 and T3 was defined as > 1 point decrease (clinically meaningful difference) in FACT-PWD score from T1. Patients were considered non-resilient if they had T2 functional decline and did not return to within 1 point of their baseline FACT-PWB score by T3. Immune cell counts, neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR) were obtained at T1. Multivariate logistic regressions were used to determine whether immune cell counts and ratios were associated with functional decline and being non-resilient controlling for baseline FACT-PWD, age, race, education, and marital status. Results: One-third of patients (178/529; mean age 53, range 22-81) had functional decline from T1-T3. Of the 59% (n = 310) of patients with functional decline at T2, 50% (n = 147) did not recover by T3 (i.e. were non-resilient). Patients with a low ( < median) NLR at T1 were twice as likely to have functional decline by T3 than those with a high (≥ median) NLR [Adjusted Odds Ratio (AOR) 1.8, 95% CI: 1.2-2.8, p < 0.01]. Similarly, in patients with functional decline at T2, those with a low NLR at T1 were twice as likely to be non-resilient than those with high NLR (AOR: 1.9, 95% CI: 1.1-3.2, p = 0.01). Conversely, patients with high T1 lymphocytes were twice as likely to be non-resilient than those with low lymphocytes (AOR: 1.8, 95% CI: 1.1-3.1, p = 0.02). Conclusions: One-third of women with breast cancer have clinically meaningful, persistent functional decline six months after completing chemotherapy. Higher pre-chemotherapy lymphocytes and lower NLR may be useful to identify which women are at increased risk of functional decline and reduced ability to regain baseline physical function. These findings can inform interventions to ameliorate this decline.