The prognostic significance of metastatic pattern in stage IV male breast cancer at initial diagnosis: a population-based study.

PURPOSE: Metastatic pattern (MP) is a prognostic factor in women with breast cancer. However, the prognostic significance of MP in male breast cancer patients remains unknown. METHODS: Using the SEER database, we gathered demographic information and disease characteristics for men diagnosed with de novo metastatic breast cancer from 2010 to 2017. Metastases to bone, brain, liver, and lung were used to define MP (bone-only, visceral, bone and visceral [BV], or other). Statistical analyses were performed to identify associations between overall survival (OS) and MP, as well as other patient and tumor features. We used multivariate logistic regression to evaluate factors associated with sites of metastases. RESULTS: We included 250 patients. MP distribution was bone = 38.8%, visceral = 14.8%, BV = 33.2%, and other = 13.2%. Median OS for each was bone = 33 months, visceral = 23 months, BV = 20 months, and other = 46 months (p = 0.046). Patients with brain metastases had significantly shorter OS compared with no brain metastases (median OS = 9 months vs. 30 months; p < 0.001). Compared with other subtypes, triple negative had the shortest OS (median 9 months, p < 0.001). Logistic regression modeling revealed that compared with HR+/HER2- breast cancers, HR-/HER2+ had higher odds of liver metastases and triple negative had higher odds of brain metastases. Patients younger than 50 years had a significantly greater risk of developing brain metastases. CONCLUSIONS: MP and tumor subtype can predict OS outcomes in men with metastatic breast cancer at diagnosis. Brain metastases confer very poor prognosis.

Prognostic Significance of Tumor Subtypes in Women With Breast Cancer According to Stage: A Population-based Study.

OBJECTIVES: The contribution of tumor subtypes (TS) in each stage of breast cancer with the use of contemporary therapies is unclear. The aim of this study was to analyze differences in overall survival (OS) by TS according to stage compared with other factors. MATERIALS AND METHODS: We evaluated women with breast cancer diagnosed between 2010 and 2013 with known estrogen receptor and progesterone receptor (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Patient characteristics were compared between TS. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Breast cancer-specific survival was a secondary endpoint. RESULTS: We included 166,054 patients. TS distribution was: 72.5% HR-positive/HER2-negative, 10.8% HR-positive/HER2-positive, 4.8% HR-negative/HER2-positive, and 12% triple-negative (TN). Patients with HR-positive/HER2-negative tumors were older, had a lower grade and presented with the earlier stage (all P<0.0001). OS was significantly different according to TS in each stage (Pinteraction<0.0001). HR-positive/HER2-negative had the best OS in stage I (3-year OS, 97.2%). In contrast, HR-positive/HER2-positive had the best 3-year OS in stage II (94.5%), stage III (87.8%), and stage IV (54.8%). There was a 40.1% difference in OS at 3 years in stage IV between TN and HR-positive/HER2-positive. Multivariate analysis adjusted for age, race, grade, histology, and marital status confirmed these results. CONCLUSIONS: Although HR-positive/HER2-negative tumors had better clinicopathologic features, the HR-positive/HER2-positive group had the best OS in most stages. OS was significantly different by TS in each of the 4 stages and these results remained significant in the multivariate model.

Overall Survival of Men and Women With Breast Cancer According to Tumor Subtype: A Population-based Study.

OBJECTIVES: To analyze differences in overall survival (OS) between male breast cancer (MBC) and female breast cancer (FBC) according to tumor subtype compared with other factors. MATERIALS AND METHODS: We evaluated men and women with breast cancer between 2010 and 2013 with known hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patient characteristics were compared between groups. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Breast cancer-specific survival was a secondary endpoint. RESULTS: We included 1187 MBC and 166,054 FBC. Median follow-up was 21 months (range, 1 to 48) for both groups. OS at 3 years for MBC and FBC was 85.6% and 90.4%, respectively (P=0.0002). MBC were more ductal, had higher grade, presented with more advanced stage and were often HR+/HER2- (each P<0.0001). MBC had worse OS than FBC in HR+/HER2- (Hazard ratio [HaR], 1.5; P=0.0005), HR+/HER2+ (HaR, 2.8; P<0.0001) and triple negative (HaR, 4.3; P<0.0001) (Pinteraction<0.02). MBC had significantly worse OS than FBC in stages I and II, but similar OS in stages III and IV (Pinteraction<0.01). In multivariate analysis, HR+/HER2+ was the only subtype with significant differences in OS between MBC and FBC (HaR, 2.0; P=0.002). CONCLUSIONS: OS was significantly different in both groups. Men had worse OS in early stages while similar OS in stages III and IV. There were significant differences in OS according to tumor subtype; compared with women, men with HR+/HER2+ tumors had twice the risk of death.

Role of difucosylated Lewis Y antigen in outcome of locally advanced cervical squamous cell carcinoma treated with cisplatin regimen.

BACKGROUND: Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens. METHODS: 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. RESULTS: Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. CONCLUSIONS: In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS.

From Molecular Biology to Clinical Trials: Toward Personalized Colorectal Cancer Therapy.

During the past years, molecular studies through high-throughput technologies have led to the confirmation of critical alterations in colorectal cancer (CRC) and the discovery of some new ones, including mutations, DNA methylations, and structural chromosomal changes. These genomic alterations might act in concert to dysregulate specific signaling pathways that normally exert their functions on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Targeted therapy against key components of altered signaling pathways has allowed an improvement in CRC treatment. However, a significant percentage of patients with CRC and metastatic CRC will not benefit from these targeted therapies and will be restricted to systemic chemotherapy. Mechanisms of resistance have been associated with specific gene alterations. To fully understand the nature and significance of the genetic and epigenetic defects in CRC that might favor a tumor evading a given therapy, much work remains. Therefore, a dynamic link between basic molecular research and preclinical studies, which ultimately constitute the prelude to standardized therapies, is very important to provide better and more effective treatments against CRC. We present an updated revision of the main molecular features of CRC and their associated therapies currently under study in clinical trials. Moreover, we performed an unsupervised classification of CRC clinical trials with the aim of obtaining an overview of the future perspectives of preclinical studies.

Expression of ERCC1 and TUBB3 in locally advanced cervical squamous cell cancer and its correlation with different therapeutic regimens.

BACKGROUND: Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III ß-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens. METHODS: ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixty-two patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors. RESULTS: Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively). CONCLUSIONS: ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents.