Analysis of the Role of Comprehensive Treatment Model in the Treatment of Prostate Cancer

The incidence of prostate cancer is gradually increasing. There are many methods for clinical treatment of prostate cancer, such as surgical treatment and endocrine treatment. In the case of advanced prostate cancer, we must not only extend patients’ survival times but also enhance their quality of life. Endocrine medications are the most effective therapy for advanced prostate cancer. This research will investigate the therapeutic impact of a complete treatment model in prostate cancer in order to discover a trustworthy clinical treatment model. This research discovered that, as compared to endocrine treatment, radical resection of prostate cancer may diminish and reach lower serum PSA levels in a short amount of time, as well as sustain low PSA levels and delay progression to castration resistance. Moreover, the comprehensive treatment mode can effectively reduce the possibility of complications. The research results show that the comprehensive treatment model can play an important role in the treatment of prostate cancer.

The Clinical Impact of Neoadjuvant Endocrine Treatment On Luminal-Like Breast Cancers and Its Prognostic Significance: Results From a Single-institution Prospective Cohort Study

Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast conserving surgery (BCS) rates, and provides an opportunity for assessing in vivo NET effectiveness and studying any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness.Methods: From 2016 to 2020, a single-institution cohort of patients treated with NET and further surgery was evaluated. In patients with Ki67≥10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered.Results: A total of 115 estrogen receptor positive (ER+)/HER2 negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0-6.0). Median maximum size in the surgical sample was 40% smaller than pretreatment size measured by ultrasound (p<.0001). Median pretreatment Ki67 expression was 20.0% (IQR: 12.0-30.0), and was reduced to 5.0% (IQR: 1.8-10.0) after four weeks, and to 2.0% (IQR: 1.0-8.0) in the surgical sample (p<.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold-change after four weeks was significantly related to a PEPI score of 0 (p<.002). No differences were observed between luminal A- and B-like tumors with regard to fold-change and PEPI score.Conclusions: In our cohort, NET has proven effective for tumor size and Ki67 downstaging. This results in a higher rate of conservative surgery, aids in therapeutic decision-making, provides prognostic information, and constitutes a safe and well-tolerated approach

Population-based Estimates of Overtreatment with Adjuvant Systemic Therapy in Early Breast-cancer Patients with Data from the Netherlands and the USA

Purpose: Although adjuvant systemic therapy (AST) helps increase breast cancer-specific survival (BCSS), there is a growing concern for overtreatment. By estimating the expected BCSS of AST using PREDICT, this study aims to quantify the number of patients treated with AST without benefit to provide estimates of overtreatment.Methods: Data of all non-metastatic unilateral breast cancer patients diagnosed in 2015 were retrieved from cancer registries from The Netherlands and the USA. The PREDICT tool was used to estimate AST survival benefit. Overtreatment was defined as the proportion of patients that would have survived regardless of or died despite AST within 10 years. Three scenarios were evaluated: actual treatment, and recommendations by the Dutch or USA guidelines.Results: 59.5% of Dutch patients were treated with AST. 6.4% (interquartile interval [IQI] = 2.5, 8.2%) was expected to survive at least 10 years due to AST, leaving 93.6% (IQI = 91.8, 97.5%) without AST benefit (overtreatment). The lowest expected amount of overtreatment was in the targeted and chemotherapy subgroup, with 86.5% (IQI = 83.4, 89.6%) overtreatment, and highest in the only endocrine treatment subgroup, with 96.7% (IQI = 96.0, 98.1%) overtreatment. Similar results were obtained using data from the USA, and guideline recommendations.Conclusion: Based on PREDICT, AST prevents 10-year breast cancer death in 6.4% of the patients treated with AST. Consequently, AST yields no survival benefit to many treated patients. Especially improved personalization of endocrine therapy is relevant, as this therapy is widely used and is associated with the highest amount of overtreatment.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients

IntroductionApproximately 20-33% of all cancer patients are treated with acid reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastro esophageal reflux disease symptoms. Palbociclib and ribociclib are weak base so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to <0.5 mg/ml when pH is above 4,5 but ribociclibs’ solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression free survival in metastatic breast cancer (mBC) patients.Patients and methodsWe enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (Letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, if no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data collected from real life retrospectively.ResultsOur study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. Of 105 patients who received Palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPI was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p<0.0001). it was determined that taking PPI was an independent predictor of shortening PFS (p<0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPI was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p=0.003). It was determined that taking PPI was single statistically independent predictor of shortening PFS (p=0.003, univariate analysis).ConclusionsOur study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement

Purpose of review: Due to the findings of current studies and the approval of novel substances for the therapy of hormone-receptor-positive breast cancer patients, the established standards of endocrine treatment are changing. The purpose of this review is to give an overview of the history of endocrine treatment, to clarify its role in the present standard of care, and to discuss the possibilities of improvement. Recent findings: Tamoxifen, aromatase inhibitors, and fulvestrant are the main drugs that have been used for decades in the therapy of hormone-receptor-positive breast cancer patients. However, since a relevant number of women suffer at some point from disease recurrence or progression, several novel substances are being investigated to overcome resistance mechanisms by interfering with certain signaling pathways, such as the PI3K/AKT/mTOR or the CDK4/6 pathways. mTOR and CDK4/6 inhibitors were the first drugs approved for this purpose and many more are in development. Summary: Endocrine treatment is one of the best tolerable cancer therapies available. Continuous investigation serves to improve patients’ outcomes and modernize the current standard of care. Considering the resistance mechanisms and substances analyzed against these, endocrine treatment of hormone-receptor-positive breast cancer is on the brink of a new era.

Atlas of Lobular Breast Cancer Models: Challenges and Strategic Directions

Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancer (BC) cases and responds well to endocrine treatment when estrogen receptor α-positive (ER+) yet differs in many biological aspects from other ER+ BC subtypes. Up to 30% of patients with ILC will develop late-onset metastatic disease up to ten years after initial tumor diagnosis and may experience failure of systemic therapy. Unfortunately, preclinical models to study ILC progression and predict the efficacy of novel therapeutics are scarce. Here, we review the current advances in ILC modeling, including cell lines and organotypic models, genetically engineered mouse models, and patient-derived xenografts. We also underscore four critical challenges that can be addressed using ILC models: drug resistance, lobular tumor microenvironment, tumor dormancy, and metastasis. Finally, we highlight the advantages of shared experimental ILC resources and provide essential considerations from the perspective of the European Lobular Breast Cancer Consortium (ELBCC), which is devoted to better understanding and translating the molecular cues that underpin ILC to clinical diagnosis and intervention. This review will guide investigators who are considering the implementation of ILC models in their research programs.

Defending two dilemmas

Ashley’s response to our recent paper argues that a fuller appreciation of the available clinical data, of the rights of children to autonomy, and of the primary purpose of gender-affirming endocrine treatment supports the rejection of both the pathway and consent dilemmas for the treatment of gender dysphoria, as raised in this journal. In this response, we highlight certain misrepresentations of our argument, and defend our conclusions against Ashley’s main objections.

The Histopathology of Carcinoma Breast with Special Reference to p53 Marker

Introduction: Breast cancer is one of the most common cancers among women in the world. The high incidence of breast carcinoma in women has inspired a thorough investigation of potentially modifiable risk variables (clinical parameters, morphological type, and biochemical indicators) for prognosis, preventative tactics, and treatment options. One of the most important prognostic indicators for breast cancer is p53. Aims and Objectives: The goal of this study was to use immunohistochemistry to assess the prevalence of p53 mutant protein in breast cancer, correlate the results with clinical and histological parameters, and establish its impact on axillary node metastasis. Materials and Methods: A clinicopathological study of 50 cases of infiltrating ductal carcinoma of the breast was performed using immunohistochemistry to examine for p53 mutant protein expression. Results: Percentage of p53 immunohistochemical positivity in this study was 22%, which is similar to other studies' reported statistics. In both the positive and negative cases of lymph node metastases, immunohistochemical data revealed an equivocal p53 status. In compared to p53 negative cases, the carcinomas with p53 positivity showed aggressive characteristics, such as greater size and higher grade. Patients with significant lymphocytic reactions to tumours, patients under 35 years of age, and those with tumours on the left side had a higher chance of receiving a positive p53 status. This study clearly shows that breast cancers with high p53 expression are generally aggressive tumours with a poor prognosis and a poor response to endocrine treatment and chemotherapy.

FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer

Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40–1.50, p = 0.44). The difference was significant when using a “post-hoc” cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3–5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.