Breast Cancer: Metastasis, Molecular Subtypes, and Overweight and Obesity in Veracruz, Mexico

Alarcón-Rojas, Carlos A.; Álvarez-Bañuelos, María Teresa; Morales-Romero, Jaime; Suárez-Díaz, Héctor; Hernández-Fonseca, Juan Carlos; Contreras-Alarcón, Guillermo

doi:10.1016/j.clbc.2018.08.003

Cited by 19 publications

(12 citation statements)

References 24 publications

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“…Obese females were estimated to have more than 50% higher risk to develop breast cancer compared to those with normal BMI 33 . Obese people tend to be associated with larger tumour size, increased lymph-node positivity, and lower survival 29 , 33 , 34 . The association between obesity and cancer risk is particularly relevant to breast cancers as they are surrounded by adipose tissue 35 , 36 .…”

Section: Discussionmentioning

confidence: 99%

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Song

Liu

et al. 2020

Nat Commun

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Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1−/− mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.

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Section: Discussionmentioning

confidence: 99%

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Song

Liu

et al. 2020

Nat Commun

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“…Regarding formal education, 65.2% had completed at least junior high school, which is consistent with economic and education levels reported by Mexican authors and other Latin American cohorts. 21 , 27 Other authors suggest that low socioeconomic status and lower education are associated with poor survival from BC, additionally, social and cultural environment may have influenced her late visit to the doctor and access to some aspects of treatment. 28 …”

Section: Discussionmentioning

confidence: 99%

Age Under 30 Years As a Predictor of Poor Survival in a Cohort of Mexican Women With Breast Cancer

et al. 2021

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Introduction Young women under 30 years with breast cancer (BC) are an emerging challenge. The purpose is to identify prognostic factors for survival in young women under 30 years of age with BC. Material and methods A retrospective cohort study was conducted among women younger than or equal to 40 years with BC and who were treated at the State Cancer Center during the period 2012–2017. Overall survival was assessed using the Kaplan–Meier method and the log-rank test. Univariate and multivariate analysis assessed survival predictors using Cox proportional hazards regression model. Results 282 young women were included. The >30-year-old subgroup showed a significant association with excess weight ( P = .002) compared to the <30-year-old group. The <30-year-old subgroup showed a poor overall survival (56.7%), as well as highly significant values in advanced clinical stages, metastatic nodules, metastasis, and neoadjuvant therapy ( P < .001). In Model 3 of the multivariate analysis, age <30 years (HR = 3.0; 95% CI 1.1 to 8.6), triple negative subtype (HR = 2.6; 95% CI 1.1 to 6.0), tumor size >5 cm HR = 2.3; 95% CI 1.03 to 5.1), and advanced clinical stages (HR = 6.6 95% CI 1.3 to 35.5) persisted as predictors. Conclusions Being very young (<30 years) is a predictor for limited survival compared to the age of 30–40 years, as well as the tumor covariates for a worse prognosis: triple negative subtype, advanced stages, positive lymph nodes, and distant metastases in liver.

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“…In HR+ HER2-patients, obesity played a negative prognostic role in both pre-menopausal and post-menopausal women in the Asian population (21). Besides, in a crosssectional study, compared with women of normal weight, obese and morbidly obese women were affected by advanced HER2+ BC with histological grades 2 or 3 (22). Wang et al found that in Hebei, China, BC patients with a high BMI were at greater risk of poor prognosis than BC patients with a low BMI, especially in patients over 50 years of age (23).…”

Section: Obesity and Outcomes Of Breast Cancermentioning

confidence: 99%

“…In HR+ HER2– patients, obesity played a negative prognostic role in both pre-menopausal and post-menopausal women in the Asian population ( 21 ). Besides, in a cross-sectional study, compared with women of normal weight, obese and morbidly obese women were affected by advanced HER2+ BC with histological grades 2 or 3 ( 22 ). Wang et al.…”

Section: Obesity and Outcomes Of Breast Cancermentioning

confidence: 99%

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

Zhao

et al. 2021

Front. Oncol.

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Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

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Breast Cancer: Metastasis, Molecular Subtypes, and Overweight and Obesity in Veracruz, Mexico

Cited by 19 publications

References 24 publications

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Age Under 30 Years As a Predictor of Poor Survival in a Cohort of Mexican Women With Breast Cancer

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

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