Our objectives were to assess the efficacy and toxicity of gemcitabine plus cisplatin as first-line therapy in metastatic breast cancer (MBC). Patients with stage IV MBC and no prior chemotherapy for metastatic disease were treated with gemcitabine 1200 mg/m on days 1 and 8, and cisplatin 75 mg/m on day 1 every 21 days. Up to 6 cycles were given. A total of 46 patients with a median age of 49 years (range 24-77) and Karnofsky performance status of 80 or above were enrolled. In total, 238 cycles were administered. Of the 42 patients evaluable for response, seven (17%) achieved a complete response and 27 (64%) a partial response, for an overall response rate of 81% [95% confidence interval (CI) 69-93%]. Median time to progression was 14.9 months (95% CI 0-30.2 months). Median duration of response was 24.2 months (95% CI 11.2-37.3 months). The median survival was 27.9 months (95% CI 23.1-32.7 months), and the 1- and 2-year survival probabilities were 71.4 and 61.4%, respectively. All patients were evaluable for toxicity, and grade 3/4 WHO toxicities included neutropenia (41.3%), anemia (8.7%), thrombocytopenia (8.7%), alopecia (26.1%) and nausea/vomiting (32.6%). We conclude that gemcitabine plus cisplatin is a highly effective and safe first-line treatment for patients with MBC. The time to progression of 14.9 months compares favorably with other standard treatments (anthracyclines, taxanes). A randomized study is required to further investigate the role of this combination as first-line treatment for MBC.

La Educación Superior en los inicios del Siglo XXI ha alcanzado una relevancia por la necesidad de su desarrollo, el cual está signado por el papel que desempeña en la sociedad, que a nivel mundial se ha convertido en una sociedad condicionada por la generación del conocimiento, el procesamiento de la información y la comunicación de símbolos, que determinan ritmos formativos que no pueden ser enfrentados por métodos tradicionales. Ello implica la necesidad de introducir cambios profundos en la Educación Superior, en su gestión sociocultural transformadora de carácter profesionalizante y sustentada en la investigación de avanzada, que por su complejidad, diversidad y a la vez, especificidad, requieren de un discurso científico e investigativo propio, para el perfeccionamiento de los procesos universitarios en su vínculo social.

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Background: We have previously identified a genetic variant, rs140068132, which has a strong protective effect on breast cancer risk. This variant is located near the estrogen receptor 1 gene (ESR1) on chromosome 6q25, a locus which has been repeatedly implicated in breast cancer risk. Women who carry two copies of the protective variant (GG) have 60-70% reduction in risk of developing breast cancer compared to women with none. The G variant has relatively high frequency in Latin American women (up to 23% in the 1000 Genomes Project Peruvians); it is only common in people of Indigenous American ancestry and almost absent in all other populations. We investigated whether the rs140068132-A/G polymorphism is associated with a specific breast cancer subtype among Peruvian women with breast cancer. Methods: Blood samples and clinical data were collected from 441 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles were generated using the Affymetrix Precision Medicine Research Array. Four major breast cancer subtypes were identified based on immunohistochemical markers (luminal A, luminal B, triple-negative, and human epidermal growth factor receptor 2 (HER2) overexpressing). Quality control of the genotyped data was performed in PLINK. Genetic ancestry was determined for each individual using ADMIXTURE. ANOVAs were performed on the proportion of genetic ancestry and disease subtype. PLINK was used to perform a binary logistic regression on the rs140068132 variant and ER status (ER-negative versus-ER positive), with age and genetic ancestry as covariates. Results: The breast cancer patients analyzed have the following average ancestry proportions: 77.3% Indigenous American, 17.4% European, 3.8% African and 1.5% East Asian. The frequency of the G allele in the Peruvian breast cancer patients is 14% (compared to 23% in healthy individuals from the 1000 Genomes Project). We found that the G allele of rs140068132 was associated with ER-negative status among cases (OR = 0.6443, P = 0.086) for both HER2 overexpressing and triple-negative. We also examined the proportions of ancestry in relation to subtypes of disease. The proportion of Indigenous American ancestry was associated with the HER2 overexpressing subtype (P = 0.06), with an average Indigenous American ancestry among these patients of 83.1% compared to 77.3% among all patients. The proportion of African ancestry was higher in women with the triple-negative subtype, with an average African ancestry of 4.8% among patients with the triple-negative subtype compared to a 3.8% average among all patients, but this trend was not statistically significant (P = 0.21). Conclusions: The lower frequency of the variant in Peruvian breast cancer cases is consistent with a protective effect in this population. We have confirmed that the protective effect of the rs140068132 variant is stronger for ER-negative subtypes. Additional analyses are under way in a larger sample of Peruvian breast cancer patients. This abstract is also being presented as Poster C051. Citation Format: K.M. Marker, T. Vidaurre, L.I. Tamayo, J.N. Vásquez, R. Meza Florez, S. Casavilca, M. Calderon, J.E. Abugattas, H.L. Gómez, H.A. Fuentes, C.L. Monge Pimentel, S. Song, D. Cherry, S. Huntsman, D. Hu, E. Ziv, L. Fejerman. A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr PR05.