Goodwin Pamela J, Ennis Marguerite, Pritchard Kathleen I, Trudeau Maureen E, Koo Jarley, Madarnas Yolanda, Hartwick Warren, Hoffman Barry, Hood Nicky
Department of Medicine, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada.
J Clin Oncol. 2002 Jan 1;20(1):42-51. doi: 10.1200/JCO.2002.20.1.42.
Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer.
A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained.
Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P <.001), which, in turn, was associated with distant recurrence and death (P <.001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively.
Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.
胰岛素是包括胰岛素样生长因子（IGF）-I和IGF-II在内的生长因子家族成员之一，通过胰岛素和IGF-I受体对正常和恶性乳腺上皮细胞发挥促有丝分裂作用。鉴于此，以及其与肥胖（乳腺癌的不良预后因素）的公认关联，我们研究了胰岛素在早期乳腺癌中的预后关联。
收集了512例无糖尿病史的早期（T1至T3，N0至N1，M0）乳腺癌女性患者组成队列并进行前瞻性观察。收集了传统预后因素和体型信息，并采集空腹血样。
空腹胰岛素与远处复发和死亡相关；胰岛素水平最高（>51.9 pmol/L）与最低（<27.0 pmol/L）四分位数组的风险比和95%置信区间（CI）分别为2.0（95%CI，1.2至3.3）和3.1（95%CI，1.7至5.7）。有证据表明胰岛素与乳腺癌预后的关联可能是非线性的。胰岛素与体重指数相关（Spearman r = 0.59，P <.001），而体重指数又与远处复发和死亡相关（P <.001）。在纳入空腹胰岛素以及可用的肿瘤和治疗相关变量的多变量分析中，胰岛素四分位数上限与下限相比，远处复发和死亡的调整后风险比分别为2.1（95%CI，1.2至3.6）和3.3（95%CI，1.5至7.0）。
空腹胰岛素水平与早期乳腺癌女性的预后相关。空腹胰岛素水平高可识别出预后不良的女性，对此应探索更有效的治疗策略。
