Abstract
Purpose: Dysmetabolism and high circulating insulin-like growth factor 1 (IGF-1) would increase breast cancer risk, but its association with survival in HER2+ breast cancer patients has not been well-studied. Herein, we aim to evaluate the prognostic value of IGF-1 and metabolic abnormalities in HER2+ population.Patients and Methods: HER2+ breast cancer patients treated in Ruijin Hospital between November 2012 and June 2017 were retrospectively analyzed. Median value of circulating IGF-1 was adopted to classify low or high IGF-1 group. Metabolic syndrome (MetS) was defined using AHA/NHLBI criteria. Overweight was defined by body mass index (BMI) ≥ 24.0 kg/m2 in Chinese population.Results: Overall, 679 patients were included and 209 had synchronous MetS. High IGF-1 level was more common in pre/peri-menopausal women (P < 0.001) and high IGFBP-3 patients (P < 0.001). After a median follow-up of 36 months, 52 patients had disease recurrences. IGF-1 level was not associated with recurrence-free survival (RFS, P = 0.620) in the whole population. However, exploratory subgroup analysis found that BMI and IGF-1 interacted in predicting RFS (P = 0.009). For non-overweight patients, high IGF-1 showed a superior 4-years RFS (91.1 vs. 85.0%; HR 0.53, 95% CI 0.27–1.00, P = 0.049) compared with patients with low IGF-1 level. In contrast, for overweight patients, high IGF-1 was associated with an impaired 4-years RFS (88.3 vs. 95.7%, HR 3.20, 95% CI 1.00–10.21, P = 0.038). Furthermore, high IGF-1 level was independently associated with better OS in the whole (HR 0.26, 95% CI 0.08–0.82, P = 0.044) as well as non-overweight population (HR 0.15, 95% CI 0.03–0.68, P = 0.005).Conclusions: IGF-1 level was not associated with RFS in HER2+ breast cancer patients. However, IGF-1 and BMI had significant interaction in disease outcome prediction in HER2+ patients. High IGF-1 was protective in non-overweight patients, but risk factor for those overweight, which deserves further evaluation.
Highlights
Breast cancer (BC) is the most common malignancy in women worldwide
A total of 529 (77.91%) patients received mastectomy, and 58.76% received sentinel lymph node biopsy (SLNB). 94.55% of the patients were diagnosed with invasive ductal carcinoma (IDC), while others had invasive lobular carcinoma, mucinous carcinoma, or mixed carcinoma, etc
We further investigated the relationship between human epidermal growth factor receptor-2 (HER2) targeted therapy efficacy and insulin-like growth factor 1 (IGF-1) level, interacted with obesity (Figure S2), and found that only in patients with body mass index (BMI) < 24.0 kg/m2 and receiving adjuvant targeted therapy, those with higher expression of IGF-1 had a tendency of superior Recurrence-free survival (RFS) than those with lower IGF-1 (Log-rank P = 0.053; Figure S2A)
Summary
Breast cancer (BC) is the most common malignancy in women worldwide. About 15–20% BC cases see overexpression of human epidermal growth factor receptor-2 (HER2), which confers more aggressive tumor biological behavior and poorer disease outcomes [2]. Node involvement, histological grade, hormone receptor status, proliferation index, HER2-enrichment intrinsic subtype and anti-HER2 therapy application are identified prognostic factors for HER2-positive population [3]. Metabolic syndrome (MetS) is a group of pathophysiological disturbances, including central obesity, insulin resistance, dyslipidemia, and elevated blood pressure. Evidence showed that adult women with MetS had a significantly increased BC risk and a worse clinical outcome [4,5,6,7,8]. It is proposed that insulin resistance and insulin-like growth factor 1 (IGF-1) system play a critical role in the association between MetS and BC risk
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