The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. We performed two case–control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor–negative-human epidermal growth factor receptor 2–positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

This study investigates the relationship between genetic ancestry, breast cancer subtypes, and survival outcomes among 951 locally advanced breast cancer cases from Argentina, Brazil, Chile, Mexico, and Uruguay, participating in the Molecular Profile of Breast Cancer Study. Array-based genotyping and ADMIXTURE analysis were used for genetic ancestry evaluation. Breast cancer subtypes were defined by IHC and the gene expression–based PAM50 algorithm. The distribution of genetic ancestry, including European, Indigenous American (IA), African (AFR), and East Asian components, revealed a heterogeneous genetic admixture across countries, with the highest IA ancestry observed in Chile (30.9%) and Mexico (30.8%). Testing the relationship between genetic ancestry and breast cancer subtypes demonstrated that a 10% increase in European ancestry was significantly associated with a 14% decrease in the odds of developing HER2-enriched breast cancer, after adjustment by age, nodal status, and the AFR component (adj. P = 0.021, luminal A as reference). Accordingly, a 10% increase in IA ancestry was associated with a 21% increase in the probability of having HER2-enriched breast cancer (adj. P = 0.022). IA ancestry also significantly increased overall survival after adjustment by age, nodal status, and AFR ancestry, although this result is controversial and may be affected by the size and heterogeneity of the Molecular Profile Breast Cancer Study cohort. Our research confirms previous findings of a high prevalence of HER2-dependent breast tumors among Hispanic/Latina women and strengthens the hypotheses of the existence of either population-specific genetic variant(s) or of other ancestry-correlated factors that impact HER2 expression in breast cancer consistently across different Latin American regions. Significance: The evidence in this work supports the idea that factors linked to genetic ancestry influence the prevalence of breast cancer subtypes in Latin America, potentially affecting treatment needs in the region.

La reinserción laboral y la reanudación de las tareas del hogar suponen el último paso en la superación del cáncer de mama (CM). evaluar si las características clínicas y el tipo de tratamiento afectan de forma negativa el desempeño en el puesto de trabajo y en el hogar. se incluyeron 119 pacientes diagnosticadas de CM precoz. Se midieron las variables laborales y las relacionadas con las tareas del hogar. al ser diagnosticadas, la mayoría de las pacientes tenía trabajo y realizaba las tareas del hogar. A los dos años de finalizado el tratamiento, el 50% de las pacientes que trabajaban continuaba trabajando y el 68.6% de estas tuvieron dificultades para retomar su trabajo. Las pacientes que no retomaron su actividad laboral fueron diagnosticadas en estadios más avanzados y tuvieron más complicaciones postoperatorias (p < 0.005). En cuanto a la ejecución de las tareas del hogar, el 83.3% tuvieron algún grado de dificultad para llevarlas a cabo. Las pacientes que fueron sometidas a vaciamiento axilar ganglionar, las que recibieron más frecuentemente apoyo psicológico y las que tuvieron más complicaciones postoperatorias realizaron las tareas del hogar con mayor esfuerzo (p < 0.005). una vez terminado el tratamiento, el 50% de las pacientes no se reincorporó a su actividad laboral. En este caso, se objetivó el efecto negativo del estadio y de las complicaciones postoperatorias (p < 0.005). Estos datos revelan que la reinserción laboral tras el diagnóstico y tratamiento del CM es complicada.

Distribution of PAM50 breast cancer subtypes according to the four most prevalent ancestral components in Latin America: European (EUR), Indigenous American (IA), African (AFR), and East Asian (EAS). Bars shown correspond to post hoc Dunn test pairwise comparisons <0.05. HER2E, HER2-enriched; LumA, luminal A; LumB, luminal B.