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Association of vitamin D deficiency and insulin resistance with breast cancer in premenopausal Algerian women: A cross-sectional study - 03/12/21

Association de la carence en vitamine D et de la résistance à l’insuline avec le cancer du sein chez la femme algérienne non ménopausée : étude transversale

Doi : 10.1016/j.ando.2021.05.002 
Rym-Ikram Mehaoudi a , Saida Adane b , Mohamed Sadouki b , Abdelaziz Melboucy c , Amel Ghozlani a , Wafa Karouche d , Farid Cherbal e , Yacine Soltani a,
a USTHB, Endocrinology team, Laboratory of Biology and Physiology, Faculty of Biological Sciences, 16111 Algiers, Algeria 
b Central Hospital Mohamed-Seghir Nekkache, Unit of Medical Oncology, 16205 Ain Naadja, Algeria 
c Senology Clinic les Amandiers, 15000 Tizi Ouzou, Algeria 
d USTHB, Department of Probability and Statistics, Faculty of Mathematics, 16111 Algiers, Algeria 
e USTHB, Molecular Genetics team, Laboratory of Cell and Molecular Biology, Faculty of Biological Sciences, 16111 Algiers, Algeria 

Corresponding author.

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Graphical abstract




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Highlights

Study in premenopausal women newly diagnosed with breast cancer (BC).
Patients with insufficient-deficient vitamin D levels had higher frequency of tumors with grade II, ER-negative, luminal B status and high Ki-67.
Significant association of vitamin D deficiency with high Ki-67 and HOMA-IR.
Vitamin D levels were significantly negatively correlated with fasting plasma insulin, fasting plasma glucose levels and HOMA-IR, but positively with BMI.
Obese patients with insulin resistance (HOMA-IR>2.5) and high insulin levels had breast tumors with high Ki-67, ER-negative/PR-negative, HER-positive and luminal B status.
Significant association of insulin resistance with HER-positive tumors in obese patients.

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Abstract

Background

Low 25(OH)D levels are mainly related to breast cancer (BC) risk in postmenopausal women, while the impact of insulin resistance (IR) on BC prognosis is controversial.

Objective

Considering the high prevalence of BC in younger Algerian women, this cross-sectional study analyzed whether vitamin D status and IR are biomarkers for breast tumor status in premenopausal women.

Methods

In 96 women (mean age, 40.96±0.65years) newly diagnosed with BC, tumor status was determined immunohistochemically, classified by molecular subtype, then correlated with body-mass index, total plasma 25(OH)D, insulin and glucose levels and HOMA-IR, using Chi2, Student t, Spearman and ANOVA tests and multivariate logistic regression.

Results

A total of 66 of the 96 patients (68.75%) showed vitamin D deficiency (9.74ng/mL). Overweight and obese patients with HOMA-IR>2.5, positive for HER2 and with high Ki-67 index had the most severe vitamin D deficiency. There was a significant association between vitamin D deficiency, high Ki-67 index (OR, 14.55; 95% CI: 3.43–82.59; P=0.00078) and IR (OR, 4.99; 95% CI: 1.27–24.47; P=0.03), and between IR and HER2-positivity (OR, 3.23; 95% CI: 1.05–10.56; P=0.04).

Conclusions

Vitamin D deficiency and IR are potential biomarkers for poorer prognosis in BC patients, independently of and/or synergically with high Ki-67 index and HER2-positivity in premenopausal overweight or obese women. The potential relationship of vitamin D receptor gene expression with breast cancer survival in Algerian patients will be investigated in a large cohort.

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Résumé

Contexte

Les faibles taux de 25 (OH) D sont principalement liés au risque de cancer du sein (CS) chez les femmes ménopausées, tandis que l’incidence de la résistance à l’insuline (RI) sur le pronostic du CS reste controversée.

Objectif

En ce qui concerne la prévalence élevée du CS chez les jeunes femmes algériennes, cette étude transversale a analysé si le statut en vitamine D et la RI peuvent être des biomarqueurs potentiels associés au statut de tumeur du sein chez les femmes non ménopausées.

Méthodes

Parmi 96 femmes (âge moyen 40,96±0,65 ans) nouvellement diagnostiquées avec le CS, le statut des tumeurs a été déterminé par immunohistochimie, classé en sous-types moléculaires, puis corrélé avec l’IMC, le niveau total de 25(OH)D, d’insuline, de glucose et du HOMA-IR, en utilisant les tests Chi2, Student-t, Spearman, Anova et le modèle de régression logistique multivariée.

Résultats

Un total de 66 patientes sur 96 (68,75 %) ont présenté des taux de vitamine D déficients (9,74ng/mL). Les patientes en surpoids ou obèses avec HOMA-IR>2,5 et HER2-positif, indice Ki-67 élevé avaient le statut de vitamine D le plus déficient. Une association significative a été observée entre une carence en vitamine D, un indice Ki-67 élevé (OR 14,55, IC95 % : 3,43–82,59, p=0,00078) et IR (OR4,99, IC95 % : 1,27–24,47, p=0,03), et entre RI et HER2-positif (OR 3,23, IC95 % : 1,05–10,56, p=0,04).

Conclusions

La carence en vitamine D et la RI, en tant que biomarqueurs potentiels, peuvent influencer un mauvais pronostic chez les patientes atteints de CS, indépendamment et/ou en synergie avec un indice Ki-67 élevé et un statut HER2-positif chez les femmes non ménopausées en surpoids et obèses. La relation potentielle de l’expression du gène du récepteur de la vitamine D dans la survie au cancer du sein chez les patientes algériennes sera étudiée sur une grande cohorte.

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Mots clés : Femmes algériennes, Cancer du sein, Vitamine D, Résistance à l’insuline, Non ménopausée.

Keywords : Algerian women, Breast cancer, Vitamin D, Insulin resistance, Premenopausal


Mappa


 This study was accepted for presentation (in part) in a poster session at the 36th Annual Meeting of the Société Française d’Endocrinologie (SFE), Marseille, 2020.
☆☆ Cette étude a été acceptée pour être présentée (en partie) lors d’une session d’affiches au 36e Congrès annuel de la Société française d’endocrinologie (SFE), Marseille, 2020.


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P. 597-605 - Dicembre 2021 Ritorno al numero
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