Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: a cohort study

Abstract

Introduction: Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings.

Methods: We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004.

Results: Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR.

Conclusions: Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.

Figure 1

Kaplan-Meier cumulative recurrence curves for breast cancer patients in the estrogen receptor/progesterone receptor negative group. The P-values for trend were calculated using the log-rank test for trend across the quartiles of adiponectin, leptin, HOMA-IR, and insulin. The hatch marks on the curves indicate times when patients were censored.

Figure 2

Kaplan-Meier cumulative recurrence curves for breast cancer patients in the estrogen receptor/progesterone receptor positive group. The P-values for trend were calculated using the log-rank test for trend across the quartiles of adiponectin, leptin, HOMA-IR, and insulin. The hatch marks on the curves indicate times when patients were censored.

Figure 3

Adjusted hazard ratio for breast cancer recurrence according to estrogen receptor/progesterone receptor status. Cox-proportional regression was used for the estimation of hazard ratios with its 95% confidence intervals and P-value for trend. Hazard ratios were adjusted for age (<40, 40 to 49, 50 to 59, or ≥60 years), alcohol consumption (none, 0.1 to 6.9, or ≥7.0 g/day), BMI (<23.0, 23.0 to 24.9, or ≥25 kg/m2), regional lymph node metastasis (negative or positive), tumor size (<2 cm or ≥2 cm), and chemotherapy (yes or no).