Potential biomarkers as a predictive factor of response to primary chemotherapy in breast cancer patients.

In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.

Potential biomarkers as a predictive factor of response to primary chemotherapy in breast cancer patients

In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.

Validation of the online PREDICT tool in a cohort of early breast cancer in Brazil.

PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.

Validation of the online PREDICT tool in a cohort of early breast cancer in Brazil

PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.

Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors.

The purpose of this study was to retrospectively review the pathologic complete response (pCR) rate from patients (n=86) with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012). Stage II patients achieved a higher response rate compared to stage III (P=0.03). The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively) and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively). Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03) and death (HR=0.21; P=0.02). In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer.

Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.

Study of chromosome damage in patients with breast cancer treated by two antineoplastic treatments.

The frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were determined in peripheral blood lymphocyte cultures from women with breast cancer treated by chemotherapy (CT) with FEC (5-fluorouracil, epirubicin, and cyclophosphamide) or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) cocktail in six CT cycles. The number of patients in each CT cycle were from 1 to 3 for SCE and 2 to 5 for CA. Samples were collected before and 48 h after CT. Although the size of the sample was limited and interindividual variability was wide, it appears that a 21-day interval between CT sessions is sufficient for cell recovery. This fact was demonstrated by the reduction in CA and SCE frequencies between cycles in parallel with the unchanged mitotic index and proliferative index values.

Effect of transitory hyperprolactinemia on in vitro fertilization of human oocytes.

OBJECTIVE: To examine the changes in plasma prolactin (PRL) during ovarian hyperstimulation (OH) and the influence of hyperprolactinemia on folliculogenesis, oocyte retrieval and in vitro fertilization (IVF) success rates and the usefulness of the metoclopramide (MCP) test in predicting the onset of hyperprolactinemia. STUDY DESIGN: Forty-nine cycles of OH were induced in 32 infertile women using follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (GI) (n = 36), also in association with gonadotropin-releasing hormone (GII) (n = 13). The MCP test (10 mg, intravenously) was performed on fertile control women (control group, n = 9) and in GI (n = 21) and GII (n = 8) patients. RESULTS: Plasma PRL and estradiol levels increased during OH, reaching maximum levels on the day preceding oocyte retrieval in GI and GII. Since these two groups exhibited similar PRL curves, they were evaluated as a single group. Patients showing an increase in PRL of > 200% presented a greater number of follicles with a mean diameter > or = 12 mm and more mature oocytes and better IVF success rates than patients with a PRL increase < or = 200%. Oocyte retrieval did not differ between the groups. The MCP test showed hyperresponsiveness in the three groups studied, but no correlation was found between the PRL increase in this test and that during OH. CONCLUSION: Plasma PRL and estradiol levels increase during OH, while the MCP test cannot predict the onset of hyperprolactinemia. Transitory hyperprolactinemia seems to be associated with an increase in the numbers of follicles with a mean diameter > or = 12 mm and with more mature oocytes and better IVF success rates.

Microinvasive carcinoma of the cervix. Analysis of prognostic factors.

INTRODUCTION: Superficially invasive neoplasias of the uterine cervix are a matter of controversy in terms of their definition, prognostic factors and selection of treatment to minimize the risk of recurrences. We reviewed our treatment to determine whether any factors affect this risk. PATIENTS AND METHODS: The present study was conducted on 59 patients seen at our service, 22 of them with early stromal invasion (IA1) and 37 with microinvasive carcinoma (IA2) according to FIGO criteria (1995). Ten patients were submitted to conization as definitive treatment, although for three of them treatment was complemented with Wertheim-Meigs surgery due to recurrence in the remaining cervix. The other 49 patients were submitted to total abdominal hysterectomy. RESULTS: Forty-four patients underwent diagnostic or therapeutic conization, and 14 of them presented involvement of the endocervical margin. Seven patients presented recurrence with involvement of the endocervical margin in five. The age of recurrence ranged from 40 to 70 years, with a mean of 52.3 years, as opposed to a general mean of 42.3 (p<0.05). Angiolymphatic invasion was positively correlated to recurrence and death (p<0.01) as well as depth of invasion. CONCLUSIONS: We conclude that the presence of a cone with an involved endocervical margin represents a high risk of recurrence and that this condition occurs in older patients who are prone to present more extensive lesions. Thus, age should be regarded as an important risk factor. Angiolymphatic invasion and depth of invasion have a poor prognosis in terms of recurrence and death.