BackgroundAberrant 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.MethodologyThis 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 Findings16 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.ConclusionsHydralazine 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.

Background. Breast cancer (BC) is the leading cause of malignancy-related deaths among women aged Յ45 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 collaborationfromthe12differentnationalcancerin-stitutes in Latin America through SLACOM, the Latin American andCaribbeanSocietyofMedicalOncology,andconductedasystematic 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 Ͻ44 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. The Oncologist 2013;18: 1298 -1306 Implications for Practice: This review illustrates that breast cancer (BC) among Latin American women is a growing burden throughout the region. The increased proportion of BC cases in young women is important because their diagnoses and tumor behavior are usually more aggressive than in their older counterparts. The findings of this study reveal that there is scarce information regarding this matter in Latin American countries, especially concerning the particular effects and complications that this group of women face during and after treatment. Also, there are no specific clinical or educational programs that focus on this population. A call to action from health policy planners, medical providers, researchers, BC patients, families, and the community in general is deserved for better care of this emergent challenge.

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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.

Background. Breast cancer (BC) is the leading cause of malignancy-related deaths among women aged Յ45 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 collaborationfromthe12differentnationalcancerin-stitutes in Latin America through SLACOM, the Latin American andCaribbeanSocietyofMedicalOncology,andconductedasystematic 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 Ͻ44 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. The Oncologist 2013;18: 1285-1297 Implications for Practice: This review illustrates that breast cancer (BC) among Latin American women is a growing burden throughout the region. The increased proportion of BC cases in young women is important because their diagnoses and tumor behavior are usually more aggressive than in their older counterparts. The findings of this study reveal that there is scarce information regarding this matter in Latin American countries, especially concerning the particular effects and complications that this group of women face during and after treatment. Also, there are no specific clinical or educational programs that focus on this population. A call to action from health policy planners, medical providers, researchers, BC patients, families, and the community in general is deserved for better care of this emergent challenge.