Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (þ) tumors; however, the factors contributing to this observation are unknown. Genomewide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2 þ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P ¼ 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2 þ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. Significance: The positive association between Indigenous American genetic ancestry and HER2 þ breast cancer suggests that the high incidence of HER2 þ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.

IntroductionBreast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study.MethodsThe PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses.ResultsThe distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables).DiscussionThe characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.

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El deterioro cognitivo inducido por quimioterapia es un proceso biológico poco entendido; sin embargo, existe evidencia de que podría afectar a pacientes en tratamiento adyuvante por cáncer de mama cuya incidencia varía ampliamente según la población en estudio, el esquema terapéutico aplicado y la metodología utilizada en su evaluación. La presente revisión busca iniciar discusiones sobre la necesidad de generar información en nuestro medio acerca de este trastorno, a fin de plantear estrategias de prevención y control por parte del personal de salud y mejorar la calidad de vida de las pacientes sometidas a este tipo de tratamiento.

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer–protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47–0.59], as well as the lower odds of developing hormone receptor negative (HR−) versus HR+ disease (OR, 0.77; 95% CI, 0.61–0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51–0.92), HR−HER2+ (OR, 0.63; 95% CI, 0.44–0.90) and HR−HER2− (OR, 0.77; 95% CI, 0.56–1.05) compared with HR+HER2−. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR− and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.