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Evidence relating to the treatment of breast cancer patients with early-stage disease has increased significantly in the past year. Abemaciclib, olaparib, and pembrolizumab are new drugs with good efficacy in the relevant patient groups. However, some questions remain unanswered. In particular, it remains unclear which premenopausal patients with hormone receptor-positive breast cancer should be spared unnecessary treatment. The question of the degree to which chemotherapy exerts a direct cytotoxic effect on the tumor or reduces ovarian function through chemotherapy could be of key importance. This group of patients could potentially be spared chemotherapy. New, previously experimental biomarker analysis methods, such as spatial analysis of gene expression (spatial transcriptomics) are gradually finding their way into large randomized phase III trials, such as the NeoTRIP trial. This in turn leads to a better understanding of the predictive factors of new therapies, for example immunotherapy. This review summarizes the scientific innovations from recent congresses such as the San Antonio Breast Cancer Symposium 2021 but also from recent publications.

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Backgrounds: Ovarian cancer is the 8th deadliest common cancer in women around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. Chemoresistant cancer cells have characteristic expressions of cancer stem cell proteins (CSCs) CD44+/CD24-, RAD6 and DDB2. The increased expression of CD44+/CD24-, RAD6, and decreased DDB2 are believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. Thus, this study's objective is to analyze the correlation between the expression of CD44+/CD24-, RAD6 and DDB2 with ovarian cancer chemoresistance. Materials and methods: This study was conducted with a prospective cohort of 64 patients who is divided into two groups (32 patients in each group) at the Obstetrics-gynecology and pathology department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All suspected ovarian cancer patients underwent cytoreductive debulking and histopathological examination. Chemotherapy was given for six series followed by six months of observation. After the observation, we determined the therapy's response with the RECIST Criteria (Response Criteria in Solid Tumors) and then classified the results into chemoresistant or chemosensitive groups. Flow cytometry blood tests were then performed to examine the expression of CD44+/CD24-, RAD6 and DDB2. Results: There was a significant relationship between increased levels of CD44+/CD24-, and RAD6 (p < 0.05) levels with the chemoresistance of ovarian cancer. The logistic regression test showed that the CD44+/CD24- was better marker. Conclusions: These results indicate that CD44+/CD24 and RAD6 expressions are significantly associated with ovarian cancer chemoresistance, and CD44+/CD24- is the better marker to predict ovarian cancer chemoresistance.

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Introduction: Women with BRCA1/2 mutations have a 11-72% increased risk of breast/ovarian cancers throughout their lifetime. The current study examines psychosocial differences between the current sample of BRCA1/2-positive women with and without cancer histories and three comparable United States (US) female samples without BRCA1/2 mutations. Methods: Sixty BRCA1/2-positive women (with and without cancer histories) were recruited through multiple private online support groups in the US. Participants completed an online survey outlining sociodemographic and genetic counseling information, and anxiety, stress, and health-related quality of life (HRQoL) outcomes. Outcomes were compared to three similar US female normative samples via independent samples t-test analyses. Results: State and trait anxiety (p = 0.00) and stress (p = 0.001) were significantly worse in the current sample of BRCA1/2-positive women compared comparable US female samples. All HRQoL domains were significantly better in the current sample except energy/vitality, which was significantly lower (p = 0.02) in the current sample. Results were stratified by cancer and recurrence status. Conclusions: This study provides insight into how a sample of BRCA1/2-positive women both with and without cancer fare post-genetic counseling as compared to three normative female populations. Results infer the need for additional education, patient-provider training, and mental health referrals to support this population in order to circumvent unintended consequences and to improve psychosocial health in those being tested for, and those who test positive for, BRCA1/2 genetic mutations.

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Breast Cancer is the most predominant form of cancer among women worldwide. It has been rigorously studied for biomarker identifications and therapeutic targets. However, various potential genes and their clinical relevance to breast cancer remain unexplored. The heterogeneity of breast cancer is one of the major challenges in early detection. Several studies have reported the significant role of alkaline phosphate (ALP) in the regulation of tumor growth and overall free survival in the pathogenesis of different cancer, including breast cancer which may offer unique therapeutic targets. Therefore, these findings demand a comprehensive study for the biogenesis of ALP genes. This study aims to expression profiling of alkaline phosphate genes in breast cancer and to identify the key pathways and molecular mechanisms underlying breast cancer proliferation and progression. In this study, the transcriptome profiling of invasive breast carcinoma samples was performed and analyzed. We identified that all the ALP genes were downregulated in both Invasive Lobular and Invasive Ductal Carcinoma patients. To understand the underlying molecular mechanism and the clinical significance for these genes in breast cancer, the expression values of genes were measured in adjacent normal and tumor tissues of patients followed by network analysis and functional enrichment analysis. The overall analysis revealed the highly aberrant expression of ALPL gene among all four ALP genes. We identified the functional significance of RUNX2 and WNT3A in deregulating ALPL. Therefore, our findings suggests that downregulation of ALPL could be a potential marker gene for invasive breast carcinoma progression towards bone metastasis.

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Introduction: It is estimated that 12.5% of women will be diagnosed with breast cancer and 1.10% with ovarian cancer during their lifetime. Although less common, women with these mutations have a 11-72% increased risk of breast/ovarian cancers and are hereditary. Genetic testing/counseling presents the opportunity to identify carriers of BRCA1/2 genetic mutations before a cancer diagnosis. Methods: Thirty-four BRCA1/2-positive women (with and without histories of breast/ovarian cancers) were recruited through online national support groups to gain a better understanding of their genetic testing/counseling perceptions and experiences. After confirming eligibility, they were invited to participate in either a telephone or webcam interview. Interview transcripts were analyzed using qualitative thematic text analysis and descriptive coding techniques. Results: Six major themes emerged, capturing the perceptions and experiences of genetic testing/counseling for these women: 1) Emotional Reactions to Results and Genetic Counseling, 2) Future Recommendations, 3) Family Solidarity and Support, 4) Experiences with the Healthcare System, 5) Preventive Concerns and Decisions, and 6) Sources Affecting Perceived Risk. Two subthemes also emerged within the first theme, which are termed "Pre-vivor," and "Testing Intuition." Conclusions: Participants indicated that genetic testing/counseling improvements would be helpful for women in this population surrounding quality care, including sensitivity training for healthcare professionals involved in testing/counseling, additional educational resources, and increased emotional and financial support. Although these recommendations may be beneficial, more widespread research with greater generalizability to disparate groups may be necessary prior to implementation.

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Tumor heterogeneity and the unclear metastasis mechanisms are the leading cause for the unavailability of effective targeted therapy for Triple-negative breast cancer (TNBC), a breast cancer (BrCa) subtype characterized by high mortality and high frequency of distant metastasis cases. The identification of prognostic biomarker can improve prognosis and personalized treatment regimes. Herein, we collected gene expression datasets representing TNBC and Non-TNBC BrCa. From the complete dataset, a subset reflecting solely known cancer driver genes was also constructed. Recursive Feature Elimination (RFE) was employed to identify top 20, 25, 30, 35, 40, 45, and 50 gene signatures that differentiate TNBC from the other BrCa subtypes. Five machine learning algorithms were employed on these selected features and on the basis of model performance evaluation, it was found that for the complete and driver dataset, XGBoost performs the best for a subset of 25 and 20 genes, respectively. Out of these 45 genes from the two datasets, 34 genes were found to be differentially regulated. The Kaplan-Meier (KM) analysis for Distant Metastasis Free Survival (DMFS) of these 34 differentially regulated genes revealed four genes, out of which two are novel that could be potential prognostic genes (POU2AF1 and S100B). Finally, interactome and pathway enrichment analyses were carried out to investigate the functional role of the identified potential prognostic genes in TNBC. These genes are associated with MAPK, PI3-AkT, Wnt, TGF-ß, and other signal transduction pathways, pivotal in metastasis cascade. These gene signatures can provide novel molecular-level insights into metastasis.

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This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this year' s most important study outcomes.

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Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials.

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The changing landscape of gynaecological and breast cancers has involved the development of more targeted and effective therapies, and improved survival. Ultimately, these changes result in an increasing number of women surviving their cancer diagnosis, with increasing emphasis on quality-of-life issues by following treatments. Many of these women experience severe menopausal symptoms associated with cancer treatments, but the hormonal nature of many gynaecological and breast cancers complicates the effective management of these symptoms. Generally, there is a paucity of high-quality data directly examining the safety of menopausal hormone therapy (MHT) following many female cancers, and more research is needed with long term follow-up to ensure the provision of comprehensive, patient-focussed care. This article aims to synthesise and evaluate the current evidence to provide comprehensive yet accessible information to clinicians to help guide treatment decisions about the use of MHT in women, who have experienced, or are at increased risk of, both gynaecological and breast cancers. These treatment decisions should often be made in a multi-disciplinary setting which encourages shared decision-making with patients.

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Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.

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BACKGROUND: The burden of ovarian cancer (OC) in low-income countries continues to increase annually. This gynecological cancer, known for its poor survival outcomes, has not attracted much interest in medical research as compared to other women's malignancies such as breast cancer. This bibliometric study was conducted to better depict the global map and the future directions of scientific productivity in the area of OC research in Morocco. METHODS: Publication trends on OC were retrospectively analyzed using a number of bibliometric parameters based on the Pubmed database and other resources. RESULTS: During the time period (1900-2018), a total number of 74 publications responding to the inclusion criteria were found and incorporated in the bibliometric analysis. This was dominated by case reports and case series on rare ovarian tumors (n = 60). In the core cluster, only 10 original studies and 3 reviews on OC were published by Moroccan researchers. After full-text appraisal for study population, only two clinical original articles included OC patients. The other clinical studies included breast cancer patients only or were suggestive of inherited OC. In addition, 3 preclinical in vitro studies were found during the literature search. The majority of these publications were covered by Pubmed and Web of Science core collection and all published in English language. The H-index of top 10 Moroccan scientists in this area didn't exceed 10. Importantly, research and review articles were frequently published in influential journals. However, the number of publications as compared to other African countries was very low. Moreover, a similar trend in terms of article per each newly diagnosed OC case, GDP per capita and per million was also noticed. For gender distribution, female scientists were first authors in the majority of these papers but less represented as leading last authors. In the complementary cluster of other article types on rare ovarian tumors, 70% of the items were published in French and approximately 60% were indexed on Pubmed. During the last five years, a marked acceleration of publishing this research category with little impact in the evidence-based practice was noticed. CONCLUSIONS: This research area in gynecologic oncology seems to be neglected and needs to be prioritized in future research projects in Morocco particularly given the aggressive behavior of this women's cancer and the few available therapeutic options. There is an unmet need for studies on OC in all fields particularly epidemiology, clinic-pathological characteristics, and survival outcomes.

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miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as 'oncomiR-1', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.

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AIM: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70-0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44-0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53-0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors. CONCLUSIONS: The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis.

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The dietary inflammatory indexTM (DII) has been shown to correlate with concentrations of several inflammatory markers and a variety of chronic disease endpoints, including cancers of various anatomic sites. We investigated whether the DII was associated with the risk for death among women with breast cancer (BrCa). This retrospective cohort study included 1453 women with BrCa, diagnosed between 1990 and 1994, and previously enrolled in a case-control study in northern Italy. With a median follow-up of 12·6 years, we observed 503 deaths, among which 398 were due to BrCa. The usual diet was assessed at BrCa diagnosis using a validated FFQ. DII scores were calculated using thirty-one foods/nutrients. Hazard ratios (HR) of death from all causes or from BrCa, with corresponding 95 % CI, were calculated using the Cox models, adjusted for age at diagnosis, tumour stage, oestrogen/progesterone receptor status and other potential confounders. The median DII score of the study women was -1·23, with a relatively narrow range (interquartile range -2·24 to -0·11), indicating a mainly anti-inflammatory diet. There was no difference in survival according to DII tertiles, neither considering all-cause mortality (HRtertile III v. I 1·00; 95 % CI 0·78, 1·28) nor BrCa-specific mortality (HRtertile III v. I 0·97; 95 % CI 0·73, 1·27). Study findings did not suggest an association between the inflammatory potential of diet, measured by the DII, and the survival of BrCa women. However, further studies are needed in populations reporting higher DII scores and a broader range of variability in the scores.

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Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development.

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Following the clinical observation of high rate of ruptures of breast implants of the French manufacturer Poly Implant Prothèse (PIP), the French Health Products Safety Agency (Afssaps) removed these products from the market in March 2010. Physical and toxicological tests confirmed the use of silicone of improper quality both for the shell and the gel filling. Until now (12/2011), no acute toxicity or mutagenicity could be observed, but 20 cases of malignancies occured in carriers of PIP-prostheses. By means of a clinical example, we summarize the official recommendations of the Afssaps and its German equivalent, the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) for diagnosis and treatment in women with PIP breast implants. Furthermore, we intend to raise awareness for the fact that the German GfE Medizintechnik and the Dutch manufacturer Rofil distributed the identical product with a different label. Supplementary, the medical and medico-legal aspects of the "PIP scandal" are discussed.

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The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case-control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patient's breast cancer risk.