Background: Breast cancer is the most common type of cancer among women in the world. Neoadjuvant chemotherapy is the standard treatment modality in locally advanced disease. Pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance to predict complete response in locally advanced breast cancer patient who underwent neoadjuvant treatment. Method: Data from 55 non-diabetic, locally advanced breast cancer patients, treated with neoadjuvant chemotherapy between 2015-2017, were retrospectively evaluated. Demographic and clinicopathologic findings were analyzed. HOMA-IR was calculated by using obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (Fasting insulin x Fasting glucose / 405). We considered cut-off of 2.5 for insulin resistance. All patients received taxane and anthracycline-based neoadjuvant chemotherapy and then were operated within an average of 4-10 weeks. Findings were analyzed using SPSS. BMI, menopausal status, clinical stage, pathological receptor subtype, Ki-67 index, grade, and insulin resistance have been assessed the effects on pathological complete response status by the Logistic Regression. Results: At the time of diagnosis, the median age was 48.5 (min 27-max 80) years. Twenty-five patients had no insulin resistance. Most common pathologic subtype was hormone receptor positive, Her-2 negative invasive ductal carcinoma. Baseline demographics and disease characteristics are outlined in Table 1. Sixteen (29%) patients had pCR. Of these 16 patients with pCR, 5 (16%) had insulin resistance and 11 (44%) did not. There was a statistically significant difference between the two groups. Insulin resistance was significantly associated with lower pCR rate. We found that patients with insulin resistance had a 3.9 times lower probability of pCR than patients without insulin resistance [OR: 3.9, 95%CI:(1.1 - 13.6); p=0.02]. Conclusion: Our results reveal that insulin resistance might be a predictive biomarker for pCR in breast cancer who underwent neoadjuvant treatment. Molecular mechanisms for these associations are not well known, therefore more comprehensive and prospective studies are needed.

Table 1: Baseline demographic and clinical findings

All patients (n=55)Insulin Resistancep
Yes (n=30)No (n=25)
Age (median) (min-max) 48.5 (27-80) 52 (29-80) 45 (27-66) 0.06 
BMI (median) (min-max) 29.6 (18.92-43.4) 33.25 (18.92-43.4) 27.01 (21-35.2) 0.015 
Waist circumference 100 (56-116) 100 (56-116) 89 (56-106) 0.7 
Hip circumference 108 (58-134) 110 (58-134) 106 (95-120) 0.5 
Fasting Glucose Level 99 (72-126) 103 (82-126) 91 (72-115) 0.003 
HDL 57 (24-96) 55 (24-83) 59 (40-96) 0.07 
LDL 124 (51-219) 120 (51-198) 139 (61-219) 0.6 
Total Cholesterol 215 (117-314) 205 (117-298) 218 (127-314) 0.5 
Trigliseride 98 (56-467) 121 (58-467) 89 (56-164) 0.007 
White Blood Cell 6700 (3100-11100) 7550 (4100-11100) 6100 (3100-8900) 0.004 
Sedimentation Rate 31 (8-78) 33 (9-58) 27 (8-78) 0.2 
CRP 3.4 (1.59-43) 4.3 (2-43) 3.3 (1.5-12.5) 0.01 
Menopause Status (n) (%) Premenopause 32 (58%) 16 (53%) 16 (69%) 0.4 
 Postmenopause 23 (42%) 14 (47%) 9 (31%)  
Clinical Stage 2A 9 (16%) 7 (23%) 2 (8%) 0.2 
 2B 18 (32%) 10 (33%) 8 (32%)  
 3A 20 (36%) 8 (27%) 12 (48%)  
 3B 7 (14%) 5 (17%) 2 (8%)  
 3C 1 (2%) 1 (4%)  
Pathologic subtype Invaziv ductal 44 (80%) 26 (87%) 18 (72%) 0.8 
 Invaziv lobular 5 (9%) 1 (3%) 4 (16%)  
 Others 6 (11%) 3 (10%) 3 (12%)  
Receptor Status HR+, HER2- 31 (56%) 17 (56%) 14 (56%) 0.7 
 HR-, HER 2 + 7 (13%) 5 (16%) 2 (8%)  
 HR+, HER2+ 9 (16%) 4 (14%) 5 (20%)  
 HR-, HER2- 8 (15%) 4 (14%) 4 (16%)  
Ki-67 index ≤ 15 13 (23%) 11 (37%) 2 (8%) 0.01 
 > 15 37 (67%) 19 (63%) 23(92%)  
Grade Grade 1 11 (20%) 11 (37%) <0.01 
 Grade 2 28 (%51) 16 (53%) 12 (48%)  
 Grade 3 16 (29%) 3 (10%) 13 (52%)  
Pathological response CR 16 (29%) 5 (16%) 11 (44%) 0.02 
 Non-CR 39 (71%) 25 (87%) 14 (56%)  
All patients (n=55)Insulin Resistancep
Yes (n=30)No (n=25)
Age (median) (min-max) 48.5 (27-80) 52 (29-80) 45 (27-66) 0.06 
BMI (median) (min-max) 29.6 (18.92-43.4) 33.25 (18.92-43.4) 27.01 (21-35.2) 0.015 
Waist circumference 100 (56-116) 100 (56-116) 89 (56-106) 0.7 
Hip circumference 108 (58-134) 110 (58-134) 106 (95-120) 0.5 
Fasting Glucose Level 99 (72-126) 103 (82-126) 91 (72-115) 0.003 
HDL 57 (24-96) 55 (24-83) 59 (40-96) 0.07 
LDL 124 (51-219) 120 (51-198) 139 (61-219) 0.6 
Total Cholesterol 215 (117-314) 205 (117-298) 218 (127-314) 0.5 
Trigliseride 98 (56-467) 121 (58-467) 89 (56-164) 0.007 
White Blood Cell 6700 (3100-11100) 7550 (4100-11100) 6100 (3100-8900) 0.004 
Sedimentation Rate 31 (8-78) 33 (9-58) 27 (8-78) 0.2 
CRP 3.4 (1.59-43) 4.3 (2-43) 3.3 (1.5-12.5) 0.01 
Menopause Status (n) (%) Premenopause 32 (58%) 16 (53%) 16 (69%) 0.4 
 Postmenopause 23 (42%) 14 (47%) 9 (31%)  
Clinical Stage 2A 9 (16%) 7 (23%) 2 (8%) 0.2 
 2B 18 (32%) 10 (33%) 8 (32%)  
 3A 20 (36%) 8 (27%) 12 (48%)  
 3B 7 (14%) 5 (17%) 2 (8%)  
 3C 1 (2%) 1 (4%)  
Pathologic subtype Invaziv ductal 44 (80%) 26 (87%) 18 (72%) 0.8 
 Invaziv lobular 5 (9%) 1 (3%) 4 (16%)  
 Others 6 (11%) 3 (10%) 3 (12%)  
Receptor Status HR+, HER2- 31 (56%) 17 (56%) 14 (56%) 0.7 
 HR-, HER 2 + 7 (13%) 5 (16%) 2 (8%)  
 HR+, HER2+ 9 (16%) 4 (14%) 5 (20%)  
 HR-, HER2- 8 (15%) 4 (14%) 4 (16%)  
Ki-67 index ≤ 15 13 (23%) 11 (37%) 2 (8%) 0.01 
 > 15 37 (67%) 19 (63%) 23(92%)  
Grade Grade 1 11 (20%) 11 (37%) <0.01 
 Grade 2 28 (%51) 16 (53%) 12 (48%)  
 Grade 3 16 (29%) 3 (10%) 13 (52%)  
Pathological response CR 16 (29%) 5 (16%) 11 (44%) 0.02 
 Non-CR 39 (71%) 25 (87%) 14 (56%)  

Citation Format: Ozkan Alan, Tugba Akin Telli, Bilge Aktas, Sinan Koca, Ilker N Ökten, Tugba Basoglu Tuylu, Nazim C Demircan, Rukiye Arikan, Ozlem Ercelep, Mustafa U Ugurlu, Handan Kaya, Serap Kaya, Nalan Akgul Babacan, Faysal Dane, Perran F Yumuk. Does insulin resistance predict complete response in breast cancer patients who underwent neoadjuvant treatment? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-18.