Insulin-like growth factor-1, metabolic abnormalities, and pathological complete remission rate in HER2-positive breast cancer patients receiving neoadjuvant therapy.

Purpose: HER2-positive breast cancer (BC) achieving pathological complete remission (pCR) after neoadjuvant therapy (NAT) had a superior disease outcome. Dysmetabolism and stimulation of insulin-like growth factor 1 (IGF-1)-axis would increase BC risk, but we are lacking data for their association with pCR in HER2-positive+ BC. We aim to evaluate the pCR predictive value of above factors in HER2-positive BC patients receiving NAT. Patients and methods: HER2-positive BC patients receiving NAT ± trastuzumab were retrospectively included between January 2013 and December 2016. Data were compared between baseline at biopsy and surgery. Median value of IGF-1 expression was used as cutoff value to classify patients into low or high group. pCR was defined as no residual invasive carcinoma in breast and axilla. Results: Overall, 101 patients were included. Metabolic syndrome was diagnosed in 29 (28.71%) with an average of 1.71±1.51 metabolic disorders at baseline, significantly increased after NAT (2.12±1.54, P<0.001). Lipid metabolism factors, including triglycerides, TC, HDL-C and LDL-C significantly worsened after NAT (all P<0.05). Average post-NAT IGF-1 was 196.14±86.03 ng/mL (vs preNAT 186.41±75.03 ng/mL, P=0.182). pCR was achieved in 29 (28.71%) patients. pCR rate was 40.00% and 17.65% for those with low or high preIGF-1 level (P=0.013). Multivariate analysis found that low IGF-1 expression, but not any other metabolic variable, was significantly associated with higher pCR rate in whole population (OR: 3.83, 95%CI: 1.32-11.11, P=0.014) or in patients receiving NAT + trastuzumab (OR: 3.93, 95%CI: 1.13-13.63, P=0.031). With a median follow-up of 29.03 (range: 10.42-56.98) months, IGF-1 level was not associated with overall survival (P=0.328) or disease-free survival (P=0.288). Conclusion: Low IGF-1 level was related with higher pCR rate in HER2-positive BC patients receiving NAT, which deserves further clinical evaluation.

Neutrophil-to-lymphocyte ratio, obesity, and breast cancer risk in Chinese population.

Breast cancer (BC), obesity, and metabolic syndrome (MetS) shared a common mechanism of dysregulated metabolism and inflammatory response in disease initiation. Neutrophil-to-lymphocyte ratio (NLR) is associated with adverse survival of BC patients. The aim of this study is to identify risk effect between NLR and BC in Chinese population with or without obesity and MetS. BC and age-matched breast benign disease (BBD) patients were retrospectively analyzed from Comprehensive Breast Health Center, Shanghai Ruijin Hospital. MetS was defined using AHA/NHLBI criteria. Individuals were classified into very low (0-1.30), low (1.31-1.67), intermediate (1.68-2.20), and high (>2.20) NLR subsets by each NLR quartile. In all, 1540 BC and 1540 BBD patients were included. Univariate and multivariate analysis found that NLR (OR: 1.27, 95% CI: 1.16-1.39, P < .001) and obesity (OR: 1.19, 95% CI: 1.00-1.42, P = .046) but not MetS (P = .060) were significantly associated with increased BC risk. Intermediate or high NLR substantially increased BC risk compared to very low NLR group (OR: 1.57, 95% CI: 1.29-1.92, P < .001; OR: 1.84, 95% CI: 1.50-2.25, P < .001; respectively) in whole population. Subgroup analysis found that the impact of higher NLR on BC risk was more obvious in patients without obesity (intermediate NLR, OR: 1.72, 95% CI: 1.37-2.16, P < .001; high NLR, OR: 1.92, 95% CI: 1.53-2.41, P < .001) or without MetS (intermediate NLR, OR: 1.70, 95% CI: 1.35-2.14, P < .001; high NLR, OR: 1.98, 95% CI: 1.57-2.51, P < .001). Higher preoperative NLR was found in BC patients compared with BBD patients. Intermediate to high NLR level substantially increased BC risk, which was more relevant for those without obesity or MetS.