Prevalence of HMTV in breast carcinomas and unaffected tissue from Mexican women.

BACKGROUND: Breast cancer is a complex multifactorial genetic disease. Among other factors, race and, to an even greater extent, viruses are known to influence the development of this heterogeneous disease. It has been reported that MMTV-like (HMTV) gene sequences with a 90 to 98% homology to mouse mammary tumor virus are found in several populations with a prevalence range of 0 to 74%. In the Mexican population, 4.2% of patients with breast cancer exhibit the presence of HMTV (MMTV-like) sequences. The aim of this study was to evaluate the presence and current prevalence of retroviral HMTV (MMTV-like) sequences in breast cancer in Mexican women. METHODS: We used nested PCR and real-time PCR with a TaqMan probe. As a positive control, we used the C3H MMTV strain inserted into pBR322 plasmid. To confirm that we had identified the HMTV sequences, we sequenced the amplicons and compared these sequences with those of MMTV and HMTV (GenBank AF033807 and AF346816). RESULTS: A total of 12.4% of breast tumors were HMTV-positive, and 15.7% of the unaffected tissue samples from 458 patients were HMTV-positive. A total of 8.3% of the patients had both HMTV-positive tumor and adjacent tissues. The HMTV-positive samples presented 98% similarity to the reported HMTV sequence. CONCLUSIONS: These results confirm that the HMTV sequence is present in breast tumors and non-affected tissues in the Mexican population. HMTV should be considered a prominent causative agent of breast cancer.

[Frequency factor Her-2/neu overexpression in patients with breast cancer]. / Frecuencia de sobrexpresión del factor Her-2/neu en pacientes con cáncer de mama.

BACKGROUND: Her-2/neu is an oncogen related with a poor prognosis and high agresivity when overexpressed in breast cancer. Main objective was analyze the frecuency of positivity or negativity ofller/neu in patients with breast cancer after surgery and their relationship with hormone receptors. We perfomed a longitudinal, retrospective, descriptive and observational trial in all patients included in the Patology Service with a determination of Her-2/neu and hormone receptors analysis, between January 1st 2007 and December 31 st 2009.We used descriptive stadistic and association tests with correlation coefficients. We analyze 893 patients. The age range was between 24 and 94 years. The 16.% of all cases overexpressed Her-2/neu (150 patients). The 4.8% (43 patients) were included in the FISII test resulting in 29 positives to Her-2/neu. There were a total of 179 cases overexpressed. Negative estrogen receptores cases were 23%, negative progesterone receptores cases were 28% and triple negative receptors cases were 19%. We analyzed independient variables with Student I resulting age with P = 0.294. We analyzed distribution variables with Pearson test resulting in negative estrogen receptors with a P = 0.0001 negative progesterone receptres with a P = 0.0001 and triple negative receptors P= 0.0001. Relationship between hormone receptors and Her-2/neu in proporlionaly inverse in other vvords when a high hormone receptors negativitvis present there is algo a Her-2/neu highly overexpressed.

Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.

Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.

[Epirubicina neoadyuvante con o sin docetaxel secuencial en el tratamiento del cáncer de mama avanzado: evaluación de la respuesta patológica completa y tolerabilidad de la quimioterapia]. / Neoadjuvant epirubicin with or without sequential docetaxel in treatment of advanced breast cancer: assessment of pathological complete response and chemotherapy tolerability.

OBJECTIVE: To assess the pathological complete response (pCR) rate after neoadjuvant chemotherapy (NC) with anthracyclines with or without taxanes in management of locally advanced breast cancer (LABC). METHOD: Patients with LABC were included. A cohort received four cycles of 5-fluorouracil [FEC] (FEC 500 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) every 3 weeks followed by four cycles of docetaxel (D) 75 mg/m2 as 1 h infusion intravenous every 3 weeks. Another cohort received six cycles of FE100C (500, 100 and 600 mg/m2). The chemotherapy was followed by surgery and radiotherapy. RESULTS: There was no statistically significant difference in overall response rate (ORR) (ORR: 78.5 vs. 85%; p = 0.299) and clinical complete response (cCR) (c CR: 20.6 vs. 33.3%; p = 0.103) for 4FEC→4D compared to 6FE100C, respectively. Instead, there was a statistically significant improved rate of pCR (30.2 vs. 16.7%; p = 0.049) and negative axillary lymph nodes (51.6 vs. 35%; p = 0.03) for 4FEC→4D compared to 6FE100C, respectively. Serious toxicity was low and non-significant in both cohorts. The logistic regression multivariate models showed that main significant predictors to obtain a pCR were 4FEC→4D NC (odds ratio [OR]: 2.7; p = 0.019) and stage IIIA (OR: 3.8; p = 0.002). CONCLUSION: This study showed that 4FEC→4D regimen with conventional dose is highly active and well tolerated in patients with LABC in our hospital.

OBJETIVO: Evaluar la tasa de respuesta patológica completa (RPc) posterior a la quimioterapia neoadyuvante (QN) con antraciclinas con o sin taxanos en el manejo del cáncer de mama localmente avanzado (CMLA). MÉTODO: Se incluyeron pacientes con CMLA. Una cohorte recibió cuatro ciclos de FEC (5-fluorouracilo 500 mg/m2, epirubicina 75 mg/m2, ciclofosfamida 500 mg/m2) cada 3 semanas seguido por cuatro ciclos de docetaxel (D) 75 mg/m2 en infusión intravenosa de 1 hora cada 3 semanas. Otra cohorte recibió seis ciclos de FE100C (500, 100 y 600 mg/m2). Se realizó cirugía posterior a la quimioterapia. RESULTADOS: No hubo diferencia estadísticamente significativa en las tasas de respuesta objetiva (78.5 vs. 85.0%; p = 0.299) ni en la respuesta clínica completa (20.6 vs. 33.3%; p = 0.103) para 4FEC→4D comparado con 6FE100C, respectivamente. En cambio, hubo una mejora significativa en la tasa de RPc (30.2 vs. 16.7%; p = 0.049) y en los ganglios linfáticos axilares negativos (51.6 vs. 35%; p = 0.03) para 4FEC→4D en comparación con 6FE100C, respectivamente. La toxicidad grave fue baja y no significativa en ambas cohortes. Los modelos multivariados de regresión logística mostraron que los principales predictores significativos para obtener una RPc fueron la QN con 4FEC→4D (odds ratio [OR]: 2.7; p = 0.019) y el estadio IIIA (OR: 3.8; p = 0.002). CONCLUSIÓN: Este estudio mostró que el régimen 4FEC→4D con dosis convencional es muy activo y bien tolerado en pacientes con CMLA en nuestro hospital.