ABSTRACT & COMMENTARY
Role of Insulin-Like Growth Factor 1 in HER2-Positive Breast Cancer Patients Results from a retrospective study
Jacob Schor, ND, FABNO
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REFERENCE
Tong Y, Wu J, Huang O, et al. IGF-1 interacted with obesity in prognosis prediction in HER2-positive breast cancer patients. Front Oncol. 2020;10:550.
For women with a history of HER2+ breast cancer who are overweight, preference is for below-average IGF-1 levels, but for those who are at a healthy weight, elevated IGF-1 levels might be preferred.
DESIGN
Retrospective study OBJECTIVE
To evaluate the prognostic value (recurrence and mortality) of insulin-like growth factor 1 (IGF-1) and metabolic abnormalities in women with a history of HER2+ breast cancer PARTICIPANTS
Researchers analyzed data from 679 Chinese breast cancer patients, all of whom were positive for human epidermal growth factor receptor 2 (HER2+) and who had been treated at Ruijin Hospital in Shanghai, China, between November 2012 and June 2017. There were 299 women whose tumors were estrogen receptor (ER) positive and 380 who had ER-negative tumors. There were 244 women under 50 years of age and 435 women 50 years of age or more. There were 394 postmenopausal participants and 285 peri/premenopausal participants. Nearly all of the women had received prior chemotherapy (n=606). Of the 679 women, 209 had metabolic syndrome (MetS) as defined by the criteria of the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI). Being overweight was defined by body mass index (BMI) ≥ 24.0 kg/m2, which is 1 BMI point lower than is customary in most studies in the United States. OUTCOME MEASURES
Researchers calculated recurrence-free survival (RFS) from the date of surgery to the first recurrent event or death from any cause. Parameters measured included BMI, fasting glucose, IGF-1, IGF binding protein 3 (IGFBP-3), insulin, C-peptide, triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Researchers divided the participants into 2 cohorts based on high or low IGF-1 levels. As tumor size, node involvement, histological grade, hormone receptor status, proliferation index, HER2-enrichment intrinsic subtype, and anti-HER2 therapy application are known prognostic factors for HER2+ cancers, the researchers tracked these parameters as well.
KEY FINDINGS
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The median IGF-1 of the participants was 160.00 ng/mL, and the researchers used this midpoint as the dividing line between low or high IGF-1. High IGF-1 (P<0.001) and high IGFBP-3 (P<0.001) were both more common in pre- and perimenopausal women. After a median of 3 years follow-up, 52 women had disease recurrence. IGF-1 levels were not associated with recurrence-free survival (RFS, P=0.620) overall (N=679). However, when BMI was taken into account, RFS analysis revealed a clear association between IGF-1 and RFS; BMI and IGF-1 interacted in predicting RFS (P=0.009). For non-overweight patients, high IGF-1 levels were associated with a superior 4-year RFS (91.1% vs 85.0%; HR 0.53, 95% CI 0.27–1.00, P=0.049) compared with non-overweight patients with low IGF-1 levels. 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) versus overweight women with low IGF. Overall, the IGF-1/IGFBP-3 ratio was much higher in the recurrent patients compared to those without recurrence (45.14 vs 40.53, P=0.030) regardless of BMI. Overall, recurrent patients also had higher C-peptide levels (2.24 vs 2.04, P=0.045). Again, the only metabolic variables that differed between those with recurrence and those disease-free were the IGF-1/IGFBP-3 ratio and circulating C-peptide level unless the groups were
10 ©2020 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2020 SUPPLEMENT—VOL. 12 , NO. 101 (SUPPL)
