Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer.

PURPOSE: Increasingly epidemiological evidence supports that environmental factors are associated with breast cancer (BC) outcomes after a BC diagnosis. Although evidence suggests that air pollution exposure is associated with higher mortality in women with BC, studies investigating potential mechanisms have been lacking. METHODS: We evaluated women with BC (N = 151) attended at the National Cancer Institute-Mexico from 2012 to 2015. We calculated 1-year average exposures to particulate matter < 2.5 µm (PM2.5) at home address before diagnosis. We used linear and logistic regression models to determine the associations between PM2.5 exposure and BC aggressiveness (tumor size, molecular phenotype). RESULTS: Average annual PM2.5 exposure of this population was 23.0 µg/m3 [standard deviation (SD)]: 1.90 µg/m3]. PM2.5 levels were positively correlated with tumor size at diagnosis (r = 0.22; p = 0.007). Multivariable linear models had a similar inference [risk ratio (RR): 1.32; 95% confidence interval (95% CI): 1.04, 1.674]. We did not observe differences in this association by age or menopause status. Further, women with triple-negative BC (TNBC) had significantly higher PM2.5 levels compared with other phenotypes (p = 0.015). Multivariable-adjusted logistic regression models assessing the association between PM2.5 and tumor size had a similar inference (RR 1.41; 95% CI 1.05, 1.89) overall for all ages and also for women who were ≤ 50 years old at diagnosis (RR 1.63; 95% CI 1.036, 2.57). CONCLUSIONS: Our findings suggest a significant association between long-term PM2.5 exposure and BC aggressiveness based on tumor size and phenotype, as well as a worse outcome.

Management of non-invasive tumours, benign tumours and breast cancer during the COVID-19 pandemic: recommendations based on a Latin American survey.

INTRODUCTION: The COVID-19 pandemic has changed health systems across the world, both in general hospitals and in oncology institutes or centres.For cancer specialists, particularly breast cancer (BC), the COVID-19 pandemic represents a combination of challenges since the hospital resources and staff have become more limited; this has obliged oncology specialists to seek a consensus and establish which patients with BC require more urgent attention and which patients can wait until there is a better control of this pandemic. The health system in Latin America has some special characteristics; in some of the countries, there are shortages which limit access to several specialities (surgery, clinical oncology and radiotherapy) in some regions. OBJECTIVE: After a systematic review of the most recent literature regarding the management of BC during the COVID-19 pandemic, the main objective is to understand the position of the different Latin American Societies of Mastology in terms of available alternatives for the treatment of BC. METHODS: After carrying out a comprehensive and exhaustive search of the most recent guides on the management of BC during the COVID-19 pandemic, the board members of the Latin American Federation of Mastology invited, via email, different specialists, all experts in BC care, to complete an anonymous survey online.The survey was distributed between 30 and 10 May 2020. The survey included 27 questions on four topics: demographic information, consultations, imaging and treatment of BC.The questionnaire was sent and then distributed to various health specialists including breast surgeons, clinical oncologists, radiation oncologists and radiologists via the Presidents of the different Latin American Societies of Mastology in 18 countries. The results are summarised as tallies based on the number of responses to each question. RESULTS: A total of 499 responses were received. The majority of the respondents were males (275 (55.11%)); 290 participants were over 45 years (58.11%).The questionnaire presented those surveyed with three possible answers (agree, disagree and neither agree nor disagree). The results reflect that there was consensus in the majority of situations presented. Only seven questions revealed disagreement among those responding. The results are presented as recommendations. CONCLUSION: The management of patients with BC presents unique challenges during the current world health situation produced by COVID-19 pandemic. Breast care specialists (surgical oncologists, breast care clinicians, clinical oncologists, radiation oncologists and radiologists) from 18 countries in Central and South America submitted through their responses and recommendations for the treatment of BC during the COVID-19 pandemic.

Molecular expression of vascular endothelial growth factor, prokineticin receptor-1 and other biomarkers in infiltrating canalicular carcinoma of the breast.

Vascular endothelial growth factor (VEGF) is important in the growth and metastasis of cancer cells. In 2001, another angiogenic factor, endocrine gland-derived VEGF (EG-VEGF), was characterized and sequenced. EG-VEGF activity appears to be restricted to endothelial cells derived from endocrine glands. At the molecular level, its expression is regulated by hypoxia and steroid hormones. Although VEGF and EG-VEGF are structurally different, they function in a coordinated fashion. Since the majority of mammary tumors are hormone-dependent, it was hypothesized that EG-VEGF would be expressed in these tumors, and therefore, represent a potential target for anti-angiogenic therapy. The aim of the present study was to assess the expression of VEGF, EG-VEGF and its receptor (prokineticin receptor-1), as well as that of breast cancer resistant protein, estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, in 50 breast samples of infiltrating canalicular carcinoma (ICC) and their correlation with tumor staging. The samples were analyzed using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Both angiogenic growth factors were identified in all samples. However, in 90% of the samples, the expression level of VEGF was significantly higher than that of EG-VEGF (P=0.024). There was no association between the expression of VEGF, EG-VEGF or its receptor with tumor stage. In ICC, the predominant angiogenic factor expressed was VEGF. The expression level of either factor was not correlated with the tumor-node-metastasis stage. Although ICC is derived from endothelial cells, EG-VEGF expression was not the predominant angiogenic/growth factor in ICC.

Breast cancer in young women in Latin America: an unmet, growing burden.

BACKGROUND: Breast cancer (BC) is the leading cause of malignancy-related deaths among women aged ≤ 45 years. There are unexplored and uncertain issues for BC in this particular group in Latin America. The aim of this study is to evaluate BC incidence and mortality among young women and related clinicopathological and survivorship aspects in this region. MATERIALS AND METHODS: Data were obtained from Globocan 2008 and the International Agency for Research on Cancer's Cancer Incidence in Five Continents series plus databases. We requested collaboration from the 12 different national cancer institutes in Latin America through SLACOM, the Latin American and Caribbean Society of Medical Oncology, and conducted a systematic literature review to obtain local data regarding the prevalence of BC among young women and their characteristics, outcomes, and survivorship-related issues. RESULTS: BC incidence and mortality proportions for Latin American women aged <44 years were higher when compared with those of developed countries (20% vs. 12% and 14% vs. 7%, respectively). We found only a few Latin American series addressing this topic, and prevalence varied between 8% and 14%. Stage II and III disease, high histological grade, and triple-negative and HER2 BC were features frequently observed among young Latin American BC patients. CONCLUSION: The rising incidence and mortality of BC in young Latin American women is a call to action in the region. It is necessary to monitor the epidemiological and clinical data through reliable cancer registries and to consider the implementation of protocols for education of patients and health professionals. This unmet, growing burden must be considered as a top priority of the national programs in the fight against BC, and models of specialized units should be implemented for this particular group of patients to provide better care for this emergent challenge.

Breast cancer in young women in Latin America: an unmet, growing burden.

UNLABELLED: Breast cancer (BC) is the leading cause of malignancy-related deaths among women aged ≤45 years. There are unexplored and uncertain issues for BC in this particular group in Latin America. The aim of this study is to evaluate BC incidence and mortality among young women and related clinicopathological and survivorship aspects in this region. MATERIALS AND METHODS: Data were obtained from Globocan 2008 and the International Agency for Research on Cancer's Cancer Incidence in Five Continents series plus databases. We requested collaboration from the 12 different national cancer institutes in Latin America through SLACOM, the Latin American and Caribbean Society of Medical Oncology, and conducted a systematic literature review to obtain local data regarding the prevalence of BC among young women and their characteristics, outcomes, and survivorship-related issues. RESULTS: BC incidence and mortality proportions for Latin American women aged <44 years were higher when compared with those of developed countries (20% vs. 12% and 14% vs. 7%, respectively). We found only a few Latin American series addressing this topic, and prevalence varied between 8% and 14%. Stage II and III disease, high histological grade, and triple-negative and HER2 BC were features frequently observed among young Latin American BC patients. CONCLUSION: The rising incidence and mortality of BC in young Latin American women is a call to action in the region. It is necessary to monitor the epidemiological and clinical data through reliable cancer registries and to consider the implementation of protocols for education of patients and health professionals. This unmet, growing burden must be considered as a top priority of the national programs in the fight against BC, and models of specialized units should be implemented for this particular group of patients to provide better care for this emergent challenge.

Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients.

PURPOSE: We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). METHODS: We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. RESULTS: No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. CONCLUSION: Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels.

Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC represents 15% of all invasive breast cancers, but some studies have suggested that its prevalence differs between races. To the authors' knowledge, no previous studies have determined the prevalence of TNBC and its risk factors among Hispanic women. METHODS: The authors identified 2074 Hispanic women with breast cancer who attended the National Cancer Institute in Mexico City from 1998 to 2008. All histopathologic and immunohistochemical diagnoses were rereviewed by a breast cancer pathologist. The prevalence of TNBC, its association with clinicopathologic characteristics, and its prognostic impact were determined. RESULTS: The median patient age at diagnosis (±standard deviation) was 50 ± 12 years. The overall prevalence of TNBC was 23.1%. Younger age (P < .001), premenopausal status (P = .002), increased parity (P = .029), hormonal contraceptive use (P = .04) high histologic grade (P < .001), and advanced disease (P < .001) were associated independently with TNBC. Postmenopausal patients who had a body mass index (BMI) <25 kg/m(2) (P = .027) or <30 kg/m(2) (P < .001) were more likely to have TNBC. In multivariate analysis, patients with TNBC had a higher risk of locoregional recurrence (LRR), lower disease-free survival (DFS) (hazard ratio, 1.62; 95% confidence interval, 1.13-2.32; P = .009), and a lower cancer-specific survival (CSS) rate (hazard ratio, 1.66; 95% confidence interval, 1.20-2.30; P = .002) than patients with non-TNBC. CONCLUSIONS: The median age at diagnosis of Hispanic women with breast cancer was 11 years younger than the average age reported in the United States. The prevalence of TNBC in this study population was higher than that reported in white women with breast cancer. TNBC was associated with a higher risk of LRR and with lower DFS and CSS than those in patients with non-TNBC.

Calcitriol inhibits Ether-à go-go potassium channel expression and cell proliferation in human breast cancer cells.

Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-à-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

[Available resources for the treatment of breast cancer in Mexico]. / Recursos disponibles para el tratamiento del cáncer de mama en México.

OBJECTIVE: Describe the resources for the treatment of breast cancer in Mexico. METHODS: Information was obtained from 23 Centros Estatales de Cáncer (State Cancer Centers, CEC), two federal hospitals and Cancerología. This study was performed in Mexico City in August/September of 2008. RESULTS: These 23 centers provide medical care for breast cancer including surgery, chemotherapy and radiotherapy; all of them validated by the Seguro Popular. The costs were defined according to clinical stage and ranged from $27,500.00 pesos for clinical stage 0 to $480,00.00 in the advanced stage. A total of 2 689 women with breast cancer have been treated; only 1% was reported with in situ carcinoma. CONCLUSIONS: An adequate medical infrastructure is in place to treat breast cancer in Mexico. The costs are high due to late diagnosis of the disease. Early detection of breast cancer is a high priority for optimal control of this disease in Mexico.

Recursos disponibles para el tratamiento del cáncer de mama en México / Available resources for the treatment of breast cancer in Mexico

OBJECTIVE: Describe the resources for the treatment of breast cancer in Mexico. METHODS: Information was obtained from 23 Centros Estatales de Cáncer (State Cancer Centers, CEC), two federal hospitals and Cancerología. This study was performed in Mexico City in August/September of 2008. RESULTS: These 23 centers provide medical care for breast cancer including surgery, chemotherapy and radiotherapy; all of them validated by the Seguro Popular. The costs were defined according to clinical stage and ranged from $27,500.00 pesos for clinical stage 0 to $480,00.00 in the advanced stage. A total of 2 689 women with breast cancer have been treated; only 1 percent was reported with in situ carcinoma. CONCLUSIONS: An adequate medical infrastructure is in place to treat breast cancer in Mexico. The costs are high due to late diagnosis of the disease. Early detection of breast cancer is a high priority for optimal control of this disease in Mexico.

OBJETIVO: Describir los recursos existentes para el tratamiento del cáncer de mama en México. MATERIAL Y MÉTODOS: Se recolectó información de 23 Centros Estatales de Cáncer (CEC), dos hospitales federales y el Instituto Nacional de Cancerología. Este estudio se realizo en México, DF, en agosto y septiembre del año 2008. RESULTADOS: Los 23 CEC ofrecen atención médica para el cáncer de mama, incluidos cirugía, quimioterapia y radioterapia, todos ellos acreditados por el Seguro Popular. Las cuotas de recuperación se definieron por etapa clínica, desde 27 500 pesos para la etapa clínica cero hasta 480 000 pesos en pacientes con enfermedad avanzada. Se ha atendido a 2 689 pacientes con cáncer de mama; sólo 1 por ciento se presentó con carcinoma in situ CONCLUSIONES: Se tiene la infraestructura y los recursos médicos para el óptimo tratamiento, pero los costos son altos debido al diagnóstico tardío. La detección oportuna del cáncer de mama es una prioridad para el óptimo control de esta enfermedad en México.

A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy.