Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives.

The advancement of immune-therapeutics in cancer treatment has proven to be promising in various malignant diseases. However, in castration resistant prostate cancer (mCRPC) major Phase III trials have been unexpectedly disappointing. To contribute to a broader understanding of the role and use of immune-therapeutics in mCRPC, we conducted a systematic review. We searched the websites ClinicalTrials.gov, PubMed and ASCO Meeting Library for clinical trials employing immune checkpoint inhibitors in mCRPC. This article not only describes the rationale of individual trials, but it also summarizes the current status of the field and sheds light on strategies for future success.

Effects of resistance exercise in prostate cancer patients: a meta-analysis.

PURPOSE: The aim of the present meta-analysis was to quantify effects of resistance exercise (RE) on physical performance and function, body composition, health-related quality of life (HRQoL), and fatigue in patients with prostate cancer. METHODS: Trial data were obtained from the databases PubMed, MEDLINE, EMBASE, SCOPUS, and the Cochrane Library as of inception to 31st of December 2016. Thirty-two trials with 1199 patients were included. Results that were measured by using the same assessment method in five or more of the original studies were pooled in a meta-analysis. RESULTS: Pooled studies showed significant improvements of muscular strength in the upper and lower body (95% CI [2.52, 7.97] kg; p < 0.001 and 95% CI [10.51, 45.88] kg; p = 0.008, respectively) after RE. Furthermore, significant improvements were seen for body composition (body fat percentage 95% CI [-0.79, -0.53] %; p < 0.001; lean body mass 95% CI [0.15, 1.84] %; p = 0.028; trunk fat mass 95% CI [-0.73, -0.08] kg; p = 0.024). Additionally, the improvement of the 400-m walk time was significant (95% CI [-21.55, -14.65] s; p < 0.001). Concerning fatigue and HRQoL, there were not sufficient data for analysis. CONCLUSIONS: RE seems to be a promising approach in order to counteract loss of muscle mass, muscle strength, and physical performance in patients suffering from prostate cancer and its treatment-related side effects. RE should play part in interdisciplinary cancer rehabilitation and care of this patient group. Nevertheless, further research should investigate RE further to determine which protocols are the most pragmatic, yet yielding best patient outcomes.

The effects of resistance exercise on physical performance and health-related quality of life in prostate cancer patients: a systematic review.

PURPOSE: Physical exercise has been shown to be an effective, safe, and quite inexpensive method to reduce cardiovascular and metabolic risk factors and is currently in the process of establishing its relevance for cancer specific morbidity and mortality. The aim of this systematic review was to focus on specific effects of resistance exercise (RE) in the adjuvant therapy and rehabilitation of prostate cancer patients (PCaPs) receiving or having received androgen deprivation therapy (ADT). METHODS: A systematic literature search focusing on relevant and peer-reviewed studies published between 1966 and September 2014, using PubMed, EMBASE, MEDLINE, SCOPUS, and Cochrane Library databases, was conducted. RESULTS: The majority of studies demonstrated RE as an effective and safe intervention to improve muscular strength and performance, fatigue and quality of life (QoL) in PCaPs, while there is inconclusive evidence concerning cardiovascular performance, body composition, blood lipids, bone mineral density (BMD), and immune response. CONCLUSION: Existing evidence leads to the conclusion that RE seems to be a safe intervention in PCaPs with beneficial effects on physical performance capacity and QoL. Nevertheless, further research in this field is urgently needed to increase understanding of exercise interventions in PCaPs.