Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study.

BACKGROUND AND PURPOSE: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. MATERIALS AND METHODS: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. RESULTS: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. INTERPRETATION: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Adjuvant anti-PD1 immunotherapy of resected skin melanoma: an example of non-personalized medicine with no overall survival benefit.

Randomized clinical trials demonstrated a recurrence-free survival benefit with adjuvant anti-programmed death-1 (anti-PD1) inhibitors of resected stage IIB-IV melanoma. However, no improvement in overall survival has been observed thus far. Furthermore, there are no predictive markers for immunotherapy response in melanoma, therefore adjuvant treatment is offered to all comers based exclusively on the pathological and clinical stages. Additionally, one year of treatment duration and the risk of chronic immune-related adverse effects may negatively impact patients´ quality of life. In this review, we will try to answer whether the currently available data on adjuvant anti-PD1 therapy of stage IIB-IV resected melanoma is sufficient to make this strategy available to all patients. We will also discuss the economic impact of this therapy on healthcare system budgets. Recent studies suggest that the high cost of cancer drugs may affect access to these agents globally by raising questions of sustainability for patients and society.

Cisplatin Monotherapy as a Treatment Option for Patients with HER-2 Negative Breast Cancer Experiencing Hepatic Visceral Crisis or Impending Visceral Crisis.

INTRODUCTION: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. METHODS: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m2, every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. RESULTS: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. CONCLUSION: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.

Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer.

INTRODUCTION: The advent of immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the management of mismatch repair deficient (MMR-d)/microsatellite instability-high (MSI-H) endometrial cancer (EC). Initially investigated as monotherapy in phase I-II clinical trials for recurrent disease, immunotherapy demonstrated remarkable activity, yielding overall response rates (ORR) ranging from 27% to 58%. Based on these promising findings, phase III trials have explored the integration of immunotherapy into first-line treatment regimens for advanced/recurrent EC in combination with chemotherapy or other agents such as tyrosine kinase inhibitors (TKIs), resulting in improved ORR, progression-free survival, and overall survival compared to the standard chemotherapy regimen of paclitaxel and carboplatin. As a result, the incorporation of ICIs with standard platinum-based chemotherapy is becoming a new standard of care in MMR-d/MSI-H EC. AREAS COVERED: This review synthesizes literature from PubMed, Embase databases, and recent congress abstracts on gynecological cancers. It covers MMR-d/MSI-H EC incidence, molecular diagnostics, clinical trial outcomes, predictive biomarkers for ICIs, patient profiles likely to benefit, resistance mechanisms, and the future of immunotherapy in this setting. EXPERT OPINION: By offering a comprehensive overview, this review delineates the pivotal role of ICIs in the management of MMR-d/MSI-H EC.

Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

Breast cancer (BC) is a heterogenous disease, with prognosis and treatment options depending on Estrogen, Progesterone receptor, and Human Epidermal Growth Factor Receptor-2 (HER-2) status. HER-2 negative, endocrine-independent BC presents a significant clinical challenge with limited treatment options. To date, promising strategies like immune checkpoint inhibitors have not yielded breakthroughs in patient prognosis. Despite being considered archaic, agents derived from natural sources, mainly plants, remain backbone of current treatment. In this context, we critically analyze novel naturally-derived drug candidates, elucidate their intricate mechanisms of action, and evaluate their pre-clinical in vitro and in vivo activity in endocrine-independent HER-2 negative BC. Since pre-clinical research success often does not directly correlate with drug approval, we focus on ongoing clinical trials to uncover current trends. Finally, we demonstrate the potential of combining cutting-edge technologies, such as antibody-drug conjugates or nanomedicine, with naturally-derived agents, offering new opportunities that utilize both traditional cytotoxic agents and new metabolites.

Antibody-drug conjugates in HER-2 negative breast cancers with poor prognosis.

Antibody drug conjugates (ADCs) comprise a rapidly growing class of targeted drugs that selectively deliver a cytotoxic agent to cancer cells, reducing the side effects associated with conventional chemotherapy. Breast cancer (BC) is a heterogeneous entity. The need for effective therapies for HER-2 negative BCs with poor prognosis, such as triple-negative or endocrine-resistant BC, remains unmet due to the lack of potential targets for treatments. These BC subtypes are not candidates for hormonal or anti-HER-2 agents. However, ongoing clinical trials exploring the use of ADCs with a wide range of targets have shown potential for this treatment modality. In this review, we present the current state of knowledge regarding the role of ADC and speculate on novel approaches including ADC combination therapies, new molecular targets, and the role of other subclasses of ADCs (bicycle drug conjugates, bispecific ADCs, immune modulating ADCs) in this clinical scenario.

Immune Checkpoint Inhibitor Related Rheumatological Complications: Cooperation between Rheumatologists and Oncologists.

In cancer, immune checkpoint inhibitors (ICIs) improve patient survival but may lead to severe immune-related adverse events (irAEs). Rheumatic irAEs are a distinct entity that are much more common in a real-life than in clinical trial reports due to their unspecific symptoms and them being a rare cause of hospitalization. This review focuses on an interdisciplinary approach to the management of rheumatic irAEs, including cooperation between oncologists, rheumatologists, and immunologists. We discuss the immunological background of rheumatic irAEs, as well as their unique clinical characteristics, differentiation from other irAEs, and treatment strategies. Importantly, steroids are not the basis of therapy, and nonsteroidal anti-inflammatory drugs should be administered in the front line with other antirheumatic agents. We also address whether patients with pre-existing rheumatic autoimmune diseases can receive ICIs and how antirheumatic agents can interfere with ICIs. Interestingly, there is a preclinical rationale for combining ICIs with immunosuppressants, particularly tumor necrosis factor α and interleukin 6 inhibitors. Regardless of the data, the mainstay in managing irAEs is interdisciplinary cooperation between oncologists and other medical specialties.

Cancer care for Ukrainian refugees during the first 6 weeks of 2022 Russian invasion - An experience of a cancer reference centre in Poland.

BACKGROUND: On 24th of February 2022, Ukrainian cancer patients had to face a new war. Here we describe an experience of the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow in providing cancer care for Ukrainian refugees during the initial 6 weeks of war. We present patients' characteristic, point out the main challenges and share initiatives undertaken. MATERIALS AND METHODS: For this cross-sectional analysis, we have gathered demographic and clinical data together with date of crossing the Polish-Ukrainian border for 112 Ukrainian refugees with cancer who had their first-time oncology consultation between 24th February and 8th April 2022. We have also implemented national guidelines and created local procedures, interventions and policies to manage this situation. RESULTS: The peak of patient inflow was the third week of War and refugees accounted for 13% of all first-time patients within that period of time. The majority of refugees were women (86%), treated radically (57%) with breast cancer (43%). Most of the patients required systemic treatment (67%). Amongst the main challenges at the time were differences in the reimbursement system, communication issues, lack of patients' documentation or tissue samples, prolonged diagnostic or treatment interruptions, increased risk of COVID-19 infections, chemotherapy side effects, and lack of procedures. Legal, procedural and organizational steps implemented at the local and national level were described. CONCLUSIONS: The Russian invasion on Ukraine forced an unexpectedly high number of Ukrainian cancer patients to seek help abroad, leading to the straining of the health care system in Poland.

Discrepancy between Tumor Size Assessed by Full-Field Digital Mammography or Ultrasonography (cT) and Pathology (pT) in a Multicenter Series of Breast Metaplastic Carcinoma Patients.

Metaplastic breast cancer (BC-Mp) presents diagnostic and therapeutic complexities, with scant literature available. Correct assessment of tumor size by ultrasound (US) and full-field digital mammography (FFDM) is crucial for treatment planning. METHODS: A retrospective cohort study was conducted on databases encompassing records of BC patients (2012-2022) at the National Research Institutes of Oncology (Warsaw, Gliwice and Krakow Branches). Inclusion criteria comprised confirmed diagnosis in postsurgical pathology reports with tumor size details (pT) and availability of tumor size from preoperative US and/or FFDM. Patients subjected to neoadjuvant systemic treatment were excluded. Demographics and clinicopathological data were gathered. RESULTS: Forty-five females were included. A total of 86.7% were triple-negative. The median age was 66 years (range: 33-89). The median pT was 41.63 mm (6-130), and eight patients were N-positive. Median tumor size assessed by US and FFDM was 31.81 mm (9-100) and 34.14 mm (0-120), respectively. Neither technique demonstrated superiority (p > 0.05), but they both underestimated the tumor size (p = 0.002 for US and p = 0.018 for FFDM). Smaller tumors (pT1-2) were statistically more accurately assessed by any technique (p < 0.001). Only pT correlated with overall survival. CONCLUSION: The risk of underestimation in tumor size assessment with US and FFDM has to be taken into consideration while planning surgical procedures for BC-Mp.

An ocean of possibilities: a review of marine organisms as sources of nanoparticles for cancer care.

Seas and oceans have been explored for the last 70 years in search of new compounds that can support the battle against cancer. Marine polysaccharides can act as nanomaterials for medical applications and marine-derived bioactive compounds can be applied for the biosynthesis of metallic and nonmetallic nanoparticles. Nanooncology can be used in numerous fields including diagnostics, serving as drug carriers or acting as drugs. This review focuses on marine-derived nanoparticles with potential oncological applications. It classifies organisms used for nanoparticle production, explains the production process, presents different types of nanoparticles with prospective applications in oncology, describes the molecular pathways responsible for numerous nanomedicine applications, tags areas of nanoparticle implementation in oncology and speculates about future directions.

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience.

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.

Development of an EORTC Item Bank for Computer-Adaptive Testing of Nausea and Vomiting.

OBJECTIVES: Nausea and vomiting (NV) remain common cancer symptoms and frequent side effects of anticancer therapies despite available antiemetics. They can lead to treatment disruption and discontinuation. NV is an important patient reported outcome in oncology. This study aimed to build an item bank for computer-adaptive testing (CAT) based on NV questions in the European Organisation for Research for Treatment of Cancer, Quality of Life for Cancer Patients (EORTC QLQ-C30) questionnaire and complete the first three phases of development as described in the EORTC Quality of Life Group guidelines. DATA SOURCES: The development followed a standard procedure. The three phases include conceptualization and literature search (phase 1); item classification, selection, formulation and rating, and expert evaluations (phase 2); and patient pretesting (phase 3). The literature search resulted in a preliminary list of 115 items. Following classification, formulation, and rating, 21 candidate items adhered to the QLQ-C30 format. Evaluation by experts (n = 11) from five countries and patients (n = 31) pretesting in Denmark, Poland, and the UK lead to a final list of 20 items. CONCLUSION: The selection, development, and refining of NV items have been described. The nature of this testing ensures an initial CAT item bank that after field testing (phase 4) and psychometric analysis is expected to provide a precise and efficient NV measurement while still being comparable to the original QLQ-C30 scale. IMPLICATIONS FOR NURSING PRACTICE: Access to reliable tools that facilitate NV comprehensive assessment is an important issue for nurses caring for patients with cancer. This CAT item bank is meant to support clinical decisions when all phases of testing are completed.

Medical students' perception of e-learning approach (MeSPeLA) - a mixed method research.

There is a discrepancy between the research exploring e-learning at medical universities in Central/Eastern and Western European countries. The aim of the MeSPeLA study was to explore the understanding, experience and expectations of Polish medical students in terms of e-learning. Questionnaire containing open-ended and closed questions supplemented by focus group discussion was validated and performed among 204 medical students in Poland before COVID-19 pandemia. Several domains: understanding of e-learning definitions; students' experience, preferences, expectations and perceptions of e-learning usefulness, advantages and disadvantages were addressed. The qualitative data were analyzed using an inductive approach. 46.0% of students chose a communication-oriented definition as the most appropriate. 7.4% claimed not to have any experience with e-learning. 76.8% of respondents indicated they had contact with e-learning. The main reported e-learning advantages were time saving and easier time management. The most common drawback was limited social interactions. The acceptance of the usage of e-learning was high. Medical undergraduates in Poland regardless of the year of studies, gender or choice of future specialization showed positive attitudes towards e-learning. Students with advanced IT skills showed a better understanding of the e-learning definition and perceived e-learning to be a more useful approach. The expectations and perceptions about e-learning in Polish medical schools seems similar to some extent to that in Western European and the United States so we can be more confident about applying some lessons from these research to Poland or other post-communist countries. Such application has been accelerated due to COVID-19 pandemia.

Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population.

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Look Into My Onco-forest - Review of Plant Natural Products with Anticancer Activity.

Cancer is a multistage process that numerous modalities including systemic treatment can treat. About half of the molecules that have been approved in the last few decades count for plant derivatives. This review presents the application of tree/shrub-derived biologically active compounds as anticancer agents. Different parts of trees/shrubs - wood, bark, branches, roots, leaves, needles, fruits, flowers, etc. - contain a wide variety of primary and secondary metabolites that demonstrate anticancer properties. Special attention was paid to phenolics (phenolic acids and polyphenols, including flavonoids and non-flavonoids (tannins, lignans, stilbenes)), essential oils, and their main constituents such as terpenes/terpenoids, phytosterols, alkaloids, and many others. The anticancer properties of these compounds are mainly attributed to their strong antioxidant properties. In vitro experiments on various cancer cell lines revealed a cytotoxic effect of tree-derived extracts. Mechanisms of anticancer action of the extracts are also listed. Examples of drugs that successfully underwent clinical trials with well-established positions in the guidelines created by oncological societies are provided. The review also focuses on directions for the future in the development of anticancer agents derived from trees/shrubs. Applying biologically active compounds derived from trees and shrubs as anticancer agents continuously seems promising in treating systemic cancer.

Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer.

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain and Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Systematic Review.

Transcutaneous electrical nerve stimulation (TENS) is the usage of a mild electrical current through electrodes that stimulate nerves. Patients with malignancies experience pain and chemotherapy-induced peripheral neuropathy. A systematic review was performed to find research evaluating the effect of TENS on these two common symptoms decreasing the quality of life in cancer patients. PubMed, the Cochrane Central Register of Controlled Trials and EMBASE were searched. Original studies, namely randomized controlled trials, quasi-randomized controlled trials and controlled clinical trials, published between April 2007 and May 2020, were considered. The quality of the selected studies was assessed. Seven papers were incorporated in a qualitative synthesis, with 260 patients in total. The studies varied in terms of design, populations, endpoints, quality, treatment duration, procedures and follow-up period. Based on the results, no strict recommendations concerning TENS usage in the cancer patient population could be issued. However, the existing evidence allows us to state that TENS is a safe procedure that may be self-administered by the patients with malignancy in an attempt to relieve different types of pain. There is a need for multi-center, randomized clinical trials with a good methodological design and adequate sample size.

Adjuvant combined therapy with trastuzumab in patients with HER2­ positive breast cancer and cardiac alterations: implications for optimal cardio­oncology care.

INTRODUCTION: Recently, the prognosis of patients with HER2­positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity. OBJECTIVES: We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2­positive BC. PATIENTS AND METHODS: We enrolled 251 patients with HER2­positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters. RESULTS: Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation. CONCLUSIONS: Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer follow­up is necessary to confirm this hypothesis. Patients with HER2­positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decision­making.