Interleukin 17 (IL-17) has a key role in inflammatory responses. Increased serum concentrations of IL-17 have been reported in patients with different types of cancer. Some studies suggest antitumor ...activity of IL-17 while others speak in favor of its association with poorer prognosis. The lack of data on IL-17 behavior
hinders the efforts to clarify the exact role of IL-17 in breast cancer patients and precludes the usage of IL-17 as potential therapeutic target.
The study included 118 patients with early invasive breast cancer. The serum concentration of IL-17A was measured before surgery and during adjuvant treatment and compared with healthy controls. The correlation of serum IL-17A concentration and different clinical and pathological parameters, including IL-17A expression in the corresponding tumor tissue samples, was analyzed.
Significantly higher serum concentrations of IL-17A were found in women with early breast cancer before surgery, but also during adjuvant treatment in comparison to healthy controls. No significant correlation to tumor tissue IL-17A expression was observed. There was a significant postoperative decrease of serum IL-17A concentrations even in patients with relatively lower preoperative values. A significant negative correlation was found between serum IL-17A concentrations and the tumor estrogen receptor expression.
The results suggest that the immune response in early breast cancer is mediated by IL-17A, particularly in triple-negative breast cancer. IL-17A-mediated inflammatory response subsides postoperatively, but IL-17A concentrations remain elevated compared to the values in healthy controls, even after the removal of the tumor.
Background
Trastuzumab and trastuzumab emtansine are specific antibody and antibody–drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast ...cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment.
Results
A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (
p
< 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment.
Conclusion
Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.
Tumor development, promotion and ability to spread depend greatly on
tumor microenvironment. Rapid growth accompanied by inadequate angiogenesis is the reason why most solid tumors contain hypoxic ...regions. Activation of hypoxia signaling pathways stimulates neoangiogenesis, alters tumor metabolism, promotes a more aggressive tumor behavior and significantly affects its responsiveness to therapy. Growing amount of evidence suggest that hypoxia induces transcription of tumor promoting genes leading to increased tumor cell proliferation and metastatic potential. Improved understanding of molecular pathways will enable establishment of useful prognostic and predictive factors, along with more effective treatment options.
Purpose
Oncologists are predisposed to developing burnout syndrome. Like other health care professionals worldwide, oncologists have endured additional, extreme challenges during the Covid-19 ...pandemic. Psychological resilience presents a potential protective mechanism against burnout. This cross-sectional study examines whether psychological resilience eased burnout syndrome among Croatian oncologists during the pandemic.
Methods
An anonymized self-reporting questionnaire was electronically distributed by the Croatian Society for Medical Oncology to 130 specialist and resident oncologists working in hospitals. Available for completion from September 6–24, 2021, the survey comprised demographic questions; the Oldenburg Burnout Inventory (OLBI), covering exhaustion and disengagement; and the Brief Resilience Scale (BRS). The response rate was 57.7%.
Results
Burnout was moderate or high for 86% of respondents, while 77% had moderate or high psychological resilience. Psychological resilience was significantly negatively correlated with the OLBI exhaustion subscale (
r
= − .54;
p
< 0.001) and the overall OLBI score (
r
= − .46;
p
< 0.001). Scheffe’s post hoc test showed that oncologists with high resilience scored significantly lower on the overall OLBI (
M
= 2.89; SD = 0.487) compared to oncologists with low resilience (
M
= 2.52; SD = 0.493).
Conclusion
The findings thus indicate that oncologists with high psychological resilience are at significantly lower risk of developing burnout syndrome. Accordingly, convenient measures to encourage psychological resilience in oncologists should be identified and implemented.
Human epidermal growth factor receptor 2 (HER2), a member of the
ErbB family of transmembrane receptor tyrosine kinases, is amplified in 20–30% of invasive breast cancers. HER2 amplification is ...associated with metastasis and reduced survival. Therapies targeting HER2 receptor are effective in adjuvant treatment and in metastatic disease. Several agents have demonstrated promising activity in HER2 metastatic breast cancer, either as monotherapy or in combination therapy, including the tyrosine-kinase inhibitors lapatinib and neratinib, and the anti-HER2 monoclonal antibodies trastuzumab, pertuzumab and trastuzumab-DM1/T-DM1/. Despite the improvement in overall survival with the addition of HER2-targeted agents to chemotherapy,many patients do not benefit fromthe agents because of inherent resistance. In addition,many patients who achive an initial response eventually acquire drug resistance. Several mechanism of resistance have been described, including mutations in other signalling pathways, expression of a truncated form of HER2, receptor crosstalk, and autophagy.
Breast cancer is the most common malignancy in females. Despite its well-established prognostic factors, our prognostic ability at an individual patient level remains limited. In this study, the ...immunohistochemical expression of B-Myb and DNA topoisomerase 2-alpha (Topo2a) was analyzed in primary tumors to identify patients with a higher risk of disease recurrence after adjuvant chemotherapy for early invasive breast cancer. We analyzed a cohort of 215 early invasive breast cancer patients having undergone surgery from 2002 to 2003 at the Zagreb University Hospital Centre, including 153 patients treated with adjuvant chemotherapy. All of them were followed-up prospectively for at least ten years according to routine institutional practice. Statistically significant correlations were found between B-Myb and Topo2a expression levels and particular well-established prognostic factors. B-Myb expression was lower in estrogen receptor (ER)-positive tumors (p=0.0773), whereas larger tumors and those with positive lymphovascular invasion displayed a statistically significantly higher B-Myb expression (p=0.0409 and p=0.0196). Higher tumor grade indicated higher Topo2a values (p=0.0102 and p=0.0069). The subgroup with the expression of both proteins above the median value had an almost statistically significantly (p=0.0613) inferior prognosis compared to the rest of the cohort. Study results showed the B-Myb and Topo2a expression to have a prognostic value in breast cancer patients after adjuvant chemotherapy, which should be additionally explored in future studies in a larger patient cohort.
Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a ...general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak.
We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies.
By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis.
In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.
An international panel of experts representing 17 European countries and Israel convened to discuss current needs and future developments in BRCA testing and counselling and to issue consensus ...recommendations. The experts agreed that, with the increasing availability of high-throughput testing platforms and the registration of poly-ADP-ribose-polymerase inhibitors, the need for genetic counselling and testing will rapidly increase in the near future. Consequently, the already existing shortage of genetic counsellors is expected to worsen and to compromise the quality of care particularly in individuals and families with suspected or proven hereditary breast or ovarian cancer. Increasing educational efforts within the breast cancer caregiver community may alleviate this limitation by enabling all involved specialities to perform genetic counselling. In the therapeutic setting, for patients with a clinical suspicion of genetic susceptibility and if the results may have an immediate impact on the therapeutic strategy, the majority voted that BRCA1/2 testing should be performed after histological diagnosis of breast cancer, regardless of oestrogen receptor and human epidermal growth factor receptor 2 (HER2) status. Experts also agreed that, in the predictive and therapeutic setting, genetic testing should be limited to individuals with a personal or family history suggestive of a BRCA1/2 pathogenic variant and should also include high-risk actionable genes beyond BRCA1/2. Of high-risk actionable genes, all pathological variants (i.e. class IV and V) should be reported; class III variants of unknown significance, should be reported provided that the current lack of clinical utility of the variant is expressly stated. Genetic counselling should always address the possibility that already tested individuals might be re-contacted in case new information on a particular variant results in a re-classification.
Oxidative stress is thought to play a major role in etiology of many cancers, including breast cancer. 8-hydroxy-2'deoxyguanosine (8-OHdG) is the most abundant marker of oxidative DNA damage. The aim ...of this study was to assess the extent of oxidative DNA damage in different breast cancer molecular surrogate subtypes to investigate the prognostic relevance and role of oxidative base lesion (8-OHdG) in the etiology of breast cancer.
8-OHdG expression was immunohistochemicaly studied on tissue microarrays constructed from 152 patients with invasive breast cancer. Expression was correlated with other prognostic factors, as well as different breast cancer molecular surrogate subtypes such as luminal A, luminal B human epidermal growth factor receptor 2 (HER2) negative, luminal B (HER2 positive), HER2-enriched ad triple-negative tumors.
Triple-negative breast carcinomas (TNBCs) were more frequently 8-OHdG negative compared with non-TNBCs (P=0.036). There was no statistically significant difference between 8-OHdG expression and other breast cancer molecular subtypes.In univariate analysis, there was no significant difference between 8-OHdG expression and breast cancer-specific death, although in multivariate analysis 8-OHdG overexpression was associated with better breast cancer-specific survival (BCSS) (odds ratio=0.04, 95% confidence interval, 0.002-0.62). In Cox regression analysis, patients with moderate and strong 8-OHdG expression had 0.9 times smaller breast cancer death hazard ratio than patients with negative 8-OHdG expression.
Oxidative stress may have less impact in the pathogenesis of TNBCs compared with other surrogate breast cancer molecular subtypes. 8-OHdG may be a promising biomarker in the prediction of prognosis for breast cancer patients.
Breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2) is considered to be HER2-positive. The novel HER2-
directed antibody drug conjugate, trastuzumab deruxtecan ...(T-DXd), is formed by covalently joining the monoclonal antibody trastuzumab with the topoisomerase I inhibitor deruxtecan. It exhibits significant anti-tumor activity in previously overtreated patients.
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