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PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients. METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1ß), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)]. RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r = 0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1ß/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases. CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.
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Surgery is not used as a criterion for staging prostate cancer, although there is evidence that the number of analyzed and affected lymph nodes have prognosis value. The aim of this study was to determine whether there are significant differences in staging criteria in patients who underwent prostatectomy compared to those who did not, and whether the number of affected and analyzed lymph nodes (LN) plays a prognostic role. In this retrospective study, a test cohort consisting of 404,210 newly diagnosed men with prostate cancer, between 2004 and 2010, was obtained from the 17 registries (Nov 2021 submission); a validation consisting of 147,719 newly diagnosed men with prostate cancer between 2004 and 2019 was obtained from the 8 registries (Nov 2021 submission). Prostate cancer-specific survival was analyzed by Kaplan-Meier curves, survival tables and Cox regression; overall survival was analyzed only to compare Harrell's C-index between different staging criteria. In initial analyses, it was observed that the prognostic value of lymph node metastasis changes according to the type of staging (clinical or pathological), which is linked to the surgical approach (prostatectomy). Compared with T4/N0/M0 patients, which are also classified as stage IVA, N1/M0 patients had a shorter [adjusted HR: 1.767 (1429-2184), p < 0.0005] and a longer [adjusted HR: 0.832 (0.740-0.935), p = 0.002] specific survival when submitted to prostatectomy or not, respectively. Analyzing separately the patients who were submitted to prostatectomy and those who were not, it was possible to obtain new LN metastasis classifications (N1: 1 + LN; N2: 2 + LNs; N3: > 2 + LNs). This new (pathological) classification of N allowed the reclassification of patients based on T and Gleason grade groups, mainly those with T3 and T4 disease. In the validation group, this new staging criterion was proven to be superior [specific survival C-index: 0.908 (0.906-0.911); overall survival C-index: 0.788 (0.786-0.791)] compared to that currently used by the AJCC [8th edition; specific survival C-index: 0.892 (0.889-0.895); overall survival C-index: 0.744 (0.741-0.747)]. In addition, an adequate number of dissected lymph nodes results in a 39% reduction in death risk [adjusted HR: 0.610 (0.498-0.747), p < 0.0005]. As main conclusion, the surgery has a major impact on prostate cancer staging, mainly modifying the effect of N on survival, and enabling the stratification of pathological N according to the number of affected LN. Such a factor, when considered as staging criteria, improves the prognosis classification.
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Ganglios Linfáticos , Neoplasias de la Próstata , Masculino , Humanos , Estadificación de Neoplasias , Estudios Retrospectivos , Pronóstico , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Metástasis Linfática/patologíaRESUMEN
Background: Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer. Methodology: A prospective study of 206 women with breast cancer analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan-Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05. Results: With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% [hazard ratio (HR): 5.149 (1.900-13.955), p = 0.001] for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index. Conclusions: Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward.
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Background: The luminal subtype accounts for ~70% of newly diagnosed breast cancer patients. Although it has a better prognosis, approximately 30% of them develop a late relapse. Identifying those patients is of interest to improve treatment decisions. Methods: A retrospective observational, single-centre study based on data from medical records of 572 non-metastatic (I-III) invasive ductal breast carcinoma patients, 448 with luminal tumours and 124 with triple-negative tumours. Kaplan-Meier, Cox regression and time-dependent Cox regression were carried out to obtain the prognosis value of risk factors. Results: During a median observation of 5.5 years, 105 distant metastasis events and 105 all-cause deaths were observed. In addition to known clinicopathological factors (i.e., age, tumour size and lymph node metastasis), the high semi-quantitative expression of both hormone receptors was associated with distant metastasis-free survival (DMFS) (adjusted hazard ratio (HaR): 0.524 (0.316-0.867), p = 0.012) and overall survival (OS) (adjusted HaR: 0.486 (0.286-0.827), p = 0.008). The stratified analysis made it possible to identify risk modification factors. Subsequent stratification by histological grade, Ki-67 and semi-quantitative PR expression or, mainly, the composite semi-quantitative expression of hormone receptors (cHR) enabled the identification of luminal breast cancer patients of adjuvant schema at higher risk for metastasis and death. However, initial analyses including patients of neoadjuvant therapy pointed to a path of subsequent stratification by cHR and histological grade, also enabling grouping of luminal breast cancer patients with similar prognosis for DMFS (cHR ≤ 4+ G2 or G3 versus triple-negative, adjusted HaR: 0.703 (0.415-1.189), p = 0.189) and OS (cHR ≤4+ G2 or G3 versus triple-negative, adjusted HaR: 0.662 (0.403-1.088), p = 0.104). Conclusion: The semi-quantitative expression of both cHR, Ki-67 proliferation index and histological grade can identify luminal breast cancer patients at greater risk of developing metastasis and death when combined in a hierarchical fashion, and could be useful for a better prognosis stratification in services from low- and middle-income countries.
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Background: Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma. Methods: This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status. Results: Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406), p = 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010), p = 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728), p = 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335), p = 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509), p = 0.004). Conclusion: The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3).
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BACKGROUND: Breast cancer is a heterogeneous disease with overexpression of several receptors, such as human epidermal receptor 2 (HER2), which is a prognostic and predictive biomarker for treatment with the anti-HER2 monoclonal antibody trastuzumab. This study aimed to test the contribution of this regimen in patients with overexpression/amplification of HER2 for periods shorter than the 1-year treatment recommendation. METHODS: A retrospective single-centre study involving 155 patients with non-metastatic (stages I-III) invasive ductal HER2+ breast carcinoma, with a median follow-up of 48.9 months after completion of adjuvant therapy, except endocrine therapy. RESULTS: About 60% of patients received trastuzumab therapy for a median time of 365 days. Although the use of trastuzumab for a short period has provided some benefit, analyses of survival with a continuous dependent variable have revealed a minimum time for improved survival. In the multivariate analysis by Cox regression, trastuzumab use duration exceeding 9 weeks resulted in protection against distant metastasis (adjusted HR: 0.307 (0.139-0.678), p = 0.004), disease progression (adjusted hazard ratio (HR) 0.353 (0.175-0.714), p = 0.004) and death (adjusted HR: 0.267 (0.105-0.678), p = 0.005), being superior to multimodal systemic therapy with chemotherapy and to endocrine therapy without trastuzumab, but inferior to almost 1 year of administration of this monoclonal antibody, especially regarding overall survival (adjusted HR: 0.203 (0.069-0.596), p = 0.004). CONCLUSION: Despite showing some benefits, the protective effect derived from a suboptimal time of trastuzumab exposure is inferior to the standard course of 1 year.
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Background: Men with non-reproductive cancers have a discrepant outcome compared to women. However, they differ significantly in the incidence of cancer type and characteristics. Methods: Patients with single primary cancer who were 18 years or older and whose data were gathered and made accessible by the Surveillance, Epidemiology, and End Results (SEER) program were included in this retrospective analysis. Kaplan-Meier curves and Cox regression before and after propensity score matching were performed to analyze the risk survival by sex. Results: Among the 1,274,118 patients included [median (range) age, 65 year (18-85+) years; 688,481 (54.9%) male]. The median follow-up was 21 months (0-191). Substantial improvements in survival were observed for both sexes during the years of inclusion analyzed, with no difference between them, reaching a reduction of almost 17% of deaths in 2010, and of almost 28% in 2015, compared to 2004. The women had a median survival of 74 months and overall mortality of 48.7%. Males had a median survival of 30 months (29.67-30.33) with an overall mortality of 56.2%. The PSM showed a reduced difference (6 months shorter median survival and 2.3% more death in men), but no change in hazards was observed compared to the unmatched analysis [adjusted HR: 0.888 (0.864-0.912) vs. 0.876 (0.866-0.886) in unmatched]. Conclusions: The discrepancy in survival between men and women is not explained only by the incidence of more aggressive and more advanced cancers in the former.