Meme kanserinde neoadjuvan kemoterapi yanıtlarını öngörmede belirleyici olarak açlık kan şekeri ve vücut kitle indeksi

Yıl 2023, , 66 - 71, 20.01.2023

Özgecan Dülgar , Seval Ay , Mahmut Gümüş

https://doi.org/10.21673/anadoluklin.1135546

Öz

Amaç: Obezite, meme kanseri gelişiminde etkili olabilen değiştirilebilir bir risk faktörüdür. Bozulmuş açlık glikozu ise metabolik sendromun bir bileşenidir ve diyabet gelişimi için önemli bir risk faktörüdür. Metabolik sendromun bu iki ana bileşeninin meme kanserinde neoadjuvan kemoterapi (NAK) yanıtı üzerindeki etkisini araştırmayı amaçladık.

Yöntemler: Ocak 2016’dan Ocak 2022’ye kadar NAK alan 161 meme kanseri hastasını geriye dönük olarak inceledik. Açlık plazma glukoz (APG) seviyeleri en az iki kez ölçüldü ve NAK’a başlamadan önceki vücut kitle indeksileri (VKİ) kaydedildi. Bozulmuş açlık glukozu, 100 ile 125 mg/dl plazma glukoz seviyeleri olarak tanımlandı. Analizler, APG seviyelerine göre 100 mg/dl’nin altındaki ve üzerindeki veya VKİ'ye göre obez (VKİ 30≥ kg/m2) ve obez olmayan (VKİ <30 kg/m2) olacak şekilde karşılaştırılarak yapıldı. NAK yanıtları Miller-Payne derecelendirme sistemine göre, grade 1 yanıtsız, grade 2 %30’dan az, grade 3 %30 ile %90 arası, grade 4 %90’dan fazla yanıt ve grade 5 patolojik tam yanıt (pTY) olacak şekilde sınıflandırıldı.

Bulgular: Bozulmuş açlık glukoz düzeyleri olan hastaların NAK sonrası patolojik yanıtlarının %70.8’i, grade 1 yanıtsız grubundaydı. Bozulmuş açlık glukozu olan hastalarda, hastalıksız sağ-kalım, normal APG’si olan hastalara göre daha kısaydı (p=0.031). Tek değişkenli analizde, klinik evrenin 3 olması (p<0,001), postmenopozal durum (p=0,037), HER-2 negatifliği (p<0,001), östrojen reseptör (ER) pozitifliği (p<0,001), progesteron reseptör (PR) pozitifliği (p<0,001) patolojik yanıtlara göre grade 1 yanıt vermeyen grupta, grade 2, grade 3 ve grade 4 olan hastalara kıyasla daha yüksekti. Çok değişkenli analizde APG, klinik evre, HER-2 (human epidermal growth factor receptor 2) durumu ve ER durumu, patolojik tam yanıt için bağımsız öngörücü faktörler olarak bulundu. VKİ’nin pTY üzerinde etkisi gösterilemedi. Çalışmamız, bozulmuş açlık glukozu olan hastalarda pTY oranının, normal APG seviyelerine sahip hastalardakinden 2,5 kat daha düşük olduğunu gösterdi [HR: 2,5, %95 CI 1.08–5.92, p=0,03].

Sonuç: Açlık plazma glukozunun hem pTY hem de nüks üzerinde istatistiksel anlamlı bir etkisi bulunmaktadır.

Anahtar Kelimeler

Kan şekeri, meme kanseri, neoadjuvan tedavi

Fasting plasma glucose and body mass index as predictors of neoadjuvant chemotherapy response in breast cancer

Öz

Aim: Obesity is a well-known modifiable risk factor for breast cancer. Impaired fasting glucose is a component of metabolic syndrome and a significant risk for diabetes. We aimed to research the effect of these two major components of metabolic syndrome on neoadjuvant chemotherapy (NAC) response in breast cancer.

Methods: We conducted 161 patients who had received NAC from January 2016 to January 2022. Fasting plasma glucose levels were measured at least two times and BMI was recorded before starting NAC. Impaired fasting glucose is defined as plasma glucose levels of 100 to 125 mg per dL. Analyses were compared into two groups according to FPG levels below or above 100 mg/dl and according to BMI obese (BMI30≥ kg/m2), or non-obese (BMI <30 kg/m2). The pathologic response was evaluated, and patients were divided into five groups according to the Miller-Payne grading system classified from grade V to I, complete pathologic response, loss of more than 90% of tumor cells, reduced 30% and 90% of tumor cells, lost less than 30% of tumor cells, and had no reduction in cellularity and no change malignant cells respectively

Results: In the pathologic responses, 70.8% of patients with impaired fasting glucose levels were grade 1 non-reduction with NAC. Disease free-survival was shorter in the group that had impaired fasting glucose than in the group that had normal fasting plasma glucose (FPG) (p=0.031). In univariate analysis clinical stage 3 (p <0.001), postmenopausal status (p=0.037), human epidermal growth factor receptor 2 (HER-2) negativity (p<0.001), estrogen receptor (ER) positivity (p <0.001), progesterone receptor (PR) positivity (p <0.001) rate were higher in grade 1 unresponsive patients compared to patients with pathological response grade 2, grade 3 and grade 4. In multivariate analysis showed that fasting plasma glucose, clinical stage, HER-2 status, and ER status were independent predictor factors for pathological complete response (pCR). BMI had no impact on pCR. Our trial showed that the ratio of pCR in patients with impaired fasting glucose was 2.5 times lower than that in patients who had normal FPG levels [HR: 2.5, 95%CI 1.08–5.92, p = 0.03].

Conclusion: Fasting plasma glucose significantly impacted both pCR and recurrence. 

Anahtar Kelimeler

Blood glucose, breast cancer, neoadjuvant therapy

Kaynakça

• Chan DSM, Vieira AR, Aune D, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;25(10):1901-14.
• Gallagher EJ, LeRoith D. Insulin, insulin resistance, obesity, and cancer. Curr Diab Rep. 2010;10(2):93-100.
• Jiralerspong S, Palla SL, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27(20):3297-302.
• Genuth SM, Palmer JP, Nathan DM. Classification and Diagnosis of Diabetes. In: rd, Cowie CC, Casagrande SS, Menke A, et al., editors. Diabetes in America. Bethesda (MD)2018.
• Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-95.
• Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-22.
• Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12(5):320-7.
• Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72.
• Tong YW, Wang G, Wu JY, et al. Insulin-like growth factor-1, metabolic abnormalities, and pathological complete remission rate in HER2-positive breast cancer patients receiving neoadjuvant therapy. Onco Targets Ther. 2019;12:3977-89.
• Ireland L, Santos A, Campbell F, et al. Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer. Oncogene. 2018;37(15):2022-36.
• Ambrosio MR, D'Esposito V, Costa V, et al. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells. Oncotarget. 2017;8(65):109000-17.
• Pizzuti L, Marchetti P, Natoli C, et al. Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: The EverExt study. Scientific Reports. 2017;7(1):10597.
• Elisia I, Yeung M, Wong J, et al. A low-carbohydrate diet containing soy protein and fish oil reduces breast but not prostate cancer in C3(1)/Tag mice. Carcinogenesis. 2022;43(2):115-25.
• Alan O, Akin Telli T, Aktas B, et al. Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment? World J Surg Oncol. 2020;18(1):242.
• Karatas F, Erdem GU, Sahin S, et al. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients. Breast. 2017;32:237-44.
• Sturgeon K, Digiovanni L, Good J, et al. Exercise-induced dose-response alterations in adiponectin and leptin levels are dependent on body fat changes in women at risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 2016;25(8):1195-200.