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Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine’s expression, such as CCL5 . Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150–0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.

DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress. High levels of DDIT4 were significantly associated with a worse prognosis in acute myeloid leukemia, breast cancer, glioblastoma multiforme, colon, skin and lung cancer. Conversely, a high DDIT4 expression was associated with an improved prognostic in gastric cancer. DDIT4 was not associated with the outcome of ovarian cancers. Analysis with data from the Cell Miner Tool in 60 cancer cell lines indicated that although rapamycin activity was correlated with levels of MTOR , it is not influenced by DDIT4 expression. In summary, DDIT4 might serve as a novel prognostic biomarker in several malignancies. DDIT4 activity could be responsible for resistance to mTOR inhibitors and is a potential candidate for the development of targeted therapy.

BackgroundBreast cancer remains a leading cause of cancer-related morbidity and mortality globally, with BRCA1/2 mutation carriers facing distinct challenges due to aggressive tumor biology and heightened risks of contralateral and secondary cancers.PurposeThis review synthesizes evidence on managing early-stage breast cancer in BRCA mutation carriers, emphasizing Latin America's heterogeneous BRCA prevalence (ranging from 5% to 25.7% across countries), which underscores the need for region-specific genetic screening. BRCA-associated tumors exhibit homologous recombination deficiency, informing therapeutic strategies such as PARP inhibitors, which exploit synthetic lethality, as demonstrated by the OlympiA trial showing Olaparib's sustained survival benefits (28% reduction in mortality risk). Imaging strategies must adapt to BRCA-related tumor phenotypes: BRCA1 carriers often present mammography-elusive tumors, favoring MRI, while abbreviated MRI protocols offer cost-effective alternatives without compromising sensitivity. Surgical decision-making balances breast-conserving surgery (BCS) and mastectomy, with studies showing comparable survival outcomes but elevated contralateral cancer risk post-BCS (10-year risk: 14%), necessitating vigilant surveillance. Contralateral prophylactic mastectomy reduces contralateral cancer risk but requires personalized risk-benefit discussions. Neoadjuvant platinum-based chemotherapy shows higher pathologic complete response rates in BRCA carriers, particularly in triple-negative subtypes, though adjuvant platinum benefits remain under investigation. Emerging immunotherapies, such as pembrolizumab in KEYNOTE-522, show promise but lack BRCA-specific efficacy data. Special considerations for transgender BRCA carriers highlight evolving screening guidelines, including mammography for hormonally treated transgender women and multimodal imaging for non-mastectomized transgender men. ConclusionsOptimizing outcomes for BRCA mutation carriers demands multidisciplinary, personalized approaches integrating genetic, regional, and clinical factors. Advances in targeted therapies, refined imaging, and risk-adapted surgery emphasize the importance of shared decision-making and ongoing research to address knowledge gaps in survivorship and equitable care.

By digital profiling of residual breast tumors after neoadjuvant therapy, the authors identify gene expression patterns that correspond with a higher risk of metastasis and recurrence. Activation of the Ras-ERK pathway through loss of DUSP4 confers therapy resistance that can be overcome by combined treatment with MEK inhibitors. Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P  = 0.2635); CDH1 (26.7% vs. 28.6%, P  = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P  = 0.1686); ARID1A (20.0% vs. 14.3%, P  = 1); MLL2 (13.3% vs. 21.4%, P  = 1) and SOX9 (33.3% vs. 0.0%, P  = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden ( P  = 0.377) or microsatellite status ( P  = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Background Breast cancer (BC) is the most common malignancy in Latin American women, but with a wide variability with respect to their mortality. This study aims to estimate the mortality rates from BC in Peruvian women and to assess mortality trends over 15 years. Methods We calculated BC age-standardized mortality rate (ASMR) per 100,000 women-years using the world standard SEGI population. We estimated joinpoint regression models for BC in Peru and its geographical areas. The spatial analysis was performed using the Moran’s I statistic. Results In a 15-year period, Peru had a mortality rate of 9.97 per 100,000 women-years. The coastal region had the highest mortality rate (12.15 per 100,000 women-years), followed by the highlands region (4.71 per 100,000 women-years). In 2003, the highest ASMR for BC were in the provinces of Lima, Arequipa, and La Libertad (above 8.0 per 100,000 women-years), whereas in 2017, the highest ASMR were in Tumbes, Callao, and Moquegua (above 13.0 per women-years). The mortality trend for BC has been declining in the coastal region since 2005 (APC = − 1.35, p  < 0.05), whereas the highlands region experienced an upward trend throughout the study period (APC = 4.26, p  < 0.05). The rainforest region had a stable trend. Spatial analysis showed a Local Indicator of Spatial Association of 0.26 (p < 0.05). Conclusion We found regional differences in the mortality trends over 15 years. Although the coastal region experienced a downward trend, the highlands had an upward mortality trend in the entire study period. It is necessary to implement tailored public health interventions to reduce BC mortality in Peru.

Human papillomavirus (HPV) infection is a common sexually transmitted infection often associated with cancer development. This study aimed to estimate the prevalence of HPV in women receiving care at the AUNA healthcare network in Peru. We conducted an observational, descriptive, cross-sectional, retrospective study. A de-identified database of HPV-positive women who underwent the BD Onclarity™ HPV Assay between December 2018 and December 2021 at Auna clinics was analyzed. The database contained information regarding age, city, and HPV type. High-risk HPV types were analyzed individually (16, 18, 31, 45, 51, 52) and pooled [P1 (33, 58), P2 (56,59,66), and P3 (35,39,68)]. The study was approved by an independent research ethics committee in Peru. Of 68,714 women included in the study, the HPV prevalence was 14.21% (N = 9765, 95%CI:13.95%-14.47%). The highest prevalence was detected in Piura (16.85%, 95%CI:15.40%-18.38%), where HPV-51, HPV-52, HPV-P1, HPV-P2, and HPV-P3 were most common compared to other Peruvian cities included in the study. In Arequipa, the prevalence was the lowest (13.58%, 95%CI:12.38%-14.85%), but the percentage prevalence of HPV-16 was the highest compared to other cities. The prevalence of multiple HPV infections was 2.88% (N = 1981, 95%CI:2.76%-3.01%), with most of them co-presenting two types of HPV (N = 1522). The most frequent co-occurrences were P2 and P3, P2 and 52, and P2 and 16. Among HPV-positive women, the mean age was 41.31 years (±9.48) and 25.29% were in the 31-35 years group. HPV-P2 was the most frequent in all age groups except in the 65-72 years group, where HPV-P3 was the most common. HPV prevalence was shown to be highest in Piura, with the most prevalent types being HPV-16, HPV-52, and HPV-P2 (HPV-56, -59, -66). HPV infection was found to be more frequent among women in the 31-35 years age group.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive biology and complex tumor evolution. Our purpose was to identify enrichment patterns of genomic alterations in metastatic triple-negative breast cancer (mTNBC). Methods: Genomic data were retrieved (mutations and copy number variations) from 550 primary TNBC tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) data sets and 58 mTNBC tumors from “Mutational Profile of Metastatic Breast Cancers” and “The Metastatic Breast Cancer Project.” Statistical analysis of microarray data between primary and metastatic tumors was performed using a chi-square test, and the percentage of mutation enrichment in mTNBC cases was estimated. P-values were adjusted for multiple testing with Benjamini-Hochberg method with a false-discovery rate (FDR) <.05. In addition, we identified dominant hallmarks of cancer in mTNBC. Results: Seven genes with mutations were enriched in mTNBC after correcting for multiple testing. These included TTN, HMCN1, RELN, PKHD1L1, DMD, FRAS1, and RYR3. Only RPS6KB2 amplification was statistically significant in mTNBC; on the contrary, deletion of the genes TET1, RHOA, EPHA5, SET, KCNJ5, ABCG4, NKX3-1, SDHB, IGF2, and BRCA1 were the most frequent. The molecular alterations related to the hallmark of “genetic instability and mutation” were predominant in mTNBC. Interestingly, the hallmark of “activating immune destruction” was the least represented in mTNBC. Conclusion: Despite the study limitations, we identified recurrent patterns of genomic alterations with potential contribution to tumor evolution. Deletions were the aberrations more commonly found in mTNBC. Several molecular alterations are potentially targetable.

Immunotherapy has changed the landscape of cancer treatment and has significantly improved the outcome of several cancer types including breast, lung, colorectal and prostate. Neoantigen recognition and immune checkpoint inhibitors are nowadays the milestones of different immunotherapeutic regimes; however, high cost, primary and acquired resistance and the high variability of responses make their extensive use difficult. The development of better predictive biomarkers that represent tumour diversity shows promise because there is a significant body of clinical data showing a spectrum of immunotherapeutic responses that might be related back to their specific characteristics. This article makes a conceptual and historical review to summarise the main advances in our understanding of the role of the immune system in cancer, while describing the methodological details that have been successfully implemented on cancer treatments and that may hold the key to improved therapeutic approaches.

Introduction Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. Methods We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. Results We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14–40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. Conclusions The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.