Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer

Vieira-Monteiro, Hayra de Andrade; Freitas-Alves, Daniely Regina; Sobral-Leite, Marcelo; Delou, João Marcos de Azevedo; Goulart-Citrangulo, Sheyla Maria Torres; Nascimento, Camila Telles do; Castro, Thales Nascimento e; Koifman, Sérgio; Perini, Jamila Alessandra; Vianna‐Jorge, Rosane

doi:10.1080/15384047.2016.1190486

Cited by 10 publications

(12 citation statements)

References 59 publications

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“…The remaining 9.1% of the patients were clinically followed up with no secondary intervention. The main protocol for adjuvant chemotherapy, comprising 89% of cases, was three cycles of cyclophosphamide, doxorubicin, and 5-fluorouracil, followed by three cycles of docetaxel 32,33…”

Section: Resultsmentioning

confidence: 99%

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Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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ABCB1 gene encodes an adenosine 5′-triphosphate–binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables. The ABCB1 expression was also evaluated in nonmalignant mammary tissues adjacent to tumors and in benign lesions. The detection of ABCB1 protein was performed by immunohistochemistry in tissue specimens of excised breasts obtained from a prospective cohort of Brazilian women with breast cancer. The association of ABCB1 protein levels with ABCB1 mRNA, gene polymorphisms, and clinical and histopathological variables was also evaluated. The Kaplan–Meier curves and multivariate Cox regression analyses were conducted to identify independent predictors of disease-free survival of patients with breast cancer. ABCB1 was detected in 86.3% (656) of breast tumors, 98.8% (606) of nonmalignant mammary tissue adjacent to tumors, and 100% (28) of benign lesions. Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [ORadj] =0.24; 95% confidence interval [CI] =0.13–0.45), lymph node status < pN2 (ORadj =0.27; 95% CI =0.10–0.71), tumor size >2 cm (ORadj =0.55; 95% CI =0.32–0.93), and hypertensive status (ORadj =0.42; 95% CI =0.24–0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (p log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21–9.91) or for those with triple-negative tumors (p log-rank =0.007; HR =11.41; 95% CI =1.29–100.67). The loss of constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.

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Section: Resultsmentioning

confidence: 99%

“…A description of this study cohort has been published previously 12. All the patients were interviewed to provide information on their clinical history and lifestyle habits.…”

Section: Methodsmentioning

confidence: 99%

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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“…The association between angiogenesis and mammary tumors has been a common subject of interest in humans and dogs [32–34]. In fact, human breast cancer progression is associated with robust angiogenic activity [35].…”

Section: Inflammatory Cells and Sustained Angiogenesismentioning

confidence: 99%

A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

Carvalho

Silva-Carvalho

Pires

et al. 2016

BioMed Research International

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Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

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“…The REMARK guidelines (REporting recommendations for tumor MARKer prognostic studies) were followed (McShane et al 2005). A description of this breast cancer cohort has already been published (Vieira-Monteiro et al 2016), but survival data were updated.…”

Section: Subjects and Study Designmentioning

confidence: 99%

“…Haplotypes (N = 1852) were inferred from samples with successful PTGS2 genotyping (N = 926), the minimum rate of successful genotyping being 93.5% for rs5275. A previous description of this cohort formation and clinical characteristics has been already published (Vieira-Monteiro et al 2016). Here, we added information concerning the frequency of comorbidities, hypertension being the most prevalent, followed by obesity and diabetes.…”

Section: Statistical Analysesmentioning

confidence: 99%

PTGS2 polymorphism rs689466 favors breast cancer recurrence in obese patients

Freitas-Alves

Vieira-Monteiro

Piranda

et al. 2018

Endocrine-Related Cancer

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Breast cancer is the leading cancer among women, and its increasing incidence is a challenge worldwide. Estrogen exposure is the main risk factor, but obesity among postmenopausal women has been shown to favor disease onset and progression. The link between obesity and mammary carcinogenesis involves elevated estrogen production and proinflammatory stimuli within the adipose tissue, with activation of the cyclooxygenase-2 pathway. Here, we evaluate the impact of the four most common cyclooxygenase-2 gene polymorphisms (rs689465, rs689466, rs20417 and rs20417), in combination with obesity, on the risk of breast cancer progression in a cohort of Brazilian breast cancer patients ( = 1038). Disease-free survival was evaluated using Kaplan-Meier curves, with multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HR). Obesity did not affect disease progression, whereas rs689466 variant genotypes increased the recurrence risk among obese patients (HR = 2.5; 95% CI = 1.4-4.3), either for luminal (HR = 2.2; 95% CI = 1.1-4.2) or HER2-like and triple-negative tumors (HR = 3.2; 95% CI = 1.2-8.5). Likewise, the haplotype *4, which contains variant rs689466, was associated with shorter disease-free survival among obese patients (HR = 3.3; 95% CI = 1.8-6.0), either in luminal (HR = 3.5; 95% CI = 1.6-7.3) or HER2-like and triple-negative (HR = 3.1; 95% CI = 1.1-8.9) tumors. Such deleterious impact of variant rs689466 on disease-free survival of obese breast cancer patients was restricted to postmenopausal women. In conclusion, cyclooxygenase-2 genotyping may add to the prognostic evaluation of obese breast cancer patients.

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Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer

Cited by 10 publications

References 59 publications

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

PTGS2 polymorphism rs689466 favors breast cancer recurrence in obese patients

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