Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review.

Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.

Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma.

OBJECTIVES: This study aimed to explore the practical organisational aspects and difficulties in the implementation of the molecular classification of endometrial carcinoma (EC), and to demonstrate its potential impact in prognostic risk group classification. METHODS: We conducted a multicentre, retrospective cohort study of 230 patients with EC diagnosed between 2019 and 2022. Sample processing, clinicopathological, treatment and follow-up data were collected. Molecular classification was obtained by p53 and mismatch repair proteins immunohistochemistry, and POLE next-generation sequencing. RESULTS: Implementation was achieved through centralization of molecular analysis. In practice, it was possible to optimise turnaround times of complete integrative reports for hysterectomy specimens to a median time of 18 workdays. If genetic study was started in endometrial biopsies before surgery, 82.0% were available at the time of multidisciplinary tumour board, compared to 8.4% if performed in hysterectomy. ECs were classified as follows: 37.8% no specific molecular profile, 31.7% p53 abnormal, 24.3% mismatch repair deficient, and 6.1% POLE mutant. Integration of these results with traditional clinicopathologic factors led to a change in prognostic risk group in 15 (6.5%) patients, most being initially allocated to high-intermediate (n = 8) and low (n = 5) risk groups. Eight patients changed to a higher risk, and 7 to a lower risk group, whereas 2 remained in the same group. CONCLUSIONS: Centralization of EC molecular classification is a feasible option for countries with limited resources. Optimization of workflows may be achieved by earlier analysis in biopsies and prioritisation of patients whose results imply changes in risk group classification.

Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers -systematic review and meta-analysis.

BACKGROUND: Triple negative breast cancers (TNBC) are associated with an aggressive clinical course, earlier recurrence and short survival. BRCA - mutated tumours represent up to 25% of all TNBC. BRCA status is being studied as a predictive biomarker of response to platinum agents. However, the predictive role of BRCA status is still uncertain in this setting. Since TNBC is a very heterogeneous group of diseases, it is important to identify subsets of TNBC patients that may benefit from platinum-based therapy. This study aims to establish if the presence of a germline BRCA mutation in women with TNBC improves the pathologic complete response (pCR) after neoadjuvant chemotherapy with platinum compounds. METHODS: An extensive literature search was performed in MEDLINE, EMBASE and LILACS databases, WHO (WHO International Clinical Trials Registry Platform) and the Cochrane Controlled Trials Register Database, for online trial registries and conference proceedings. The measurement of pCR was assessed by pathology review of breast specimen and lymph nodes. RESULTS: The overall OR was computed using random effects models.Seven studies were included, comprising a total of 808 TNBC patients, among which 159 were BRCA mutated. Among mutated TNBC patients, 93 (93/159; 58.4%) achieved pCR, while 410 wildtype patients (410/808; 50.7%) showed pCR (OR 1.459 CI 95% [0.953-2.34] p = 0.082) although this result did not reach statistical significance. CONCLUSIONS: This meta-analysis shows that the addition of platinum to chemotherapy regimens in the neoadjuvant setting increases pCR rate in BRCA - mutated as compared to wild-type TNBC patients. However, this trend did not achieve statistical significance. TRIAL REGISTRATION: CRD42018092341.

Neoadjuvant chemotherapy in advanced vulvar cancer.

INTRODUCTION: Locally advanced tumors of the vulva represent approximately one third of all vulvar cancers. Therapeutic options include chemoradiation, radiotherapy, and neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: Analysis of 3 NACT schemes, bleomicine, paclitaxel, and 5-fluorouracil/cisplatin, used in patients with locally advanced vulvar tumors in a 12-year period. The following parameters were evaluated and compared between regimens: age, initial tumor size, inguinal involvement, histological type, toxicities, response to treatment, surgery performed after NACT, and overall survival. RESULTS: Of the 25 patients included, 10 underwent an NACT regimen with bleomicine (Group A); 5, with paclitaxel (Group B); and 10, with a combination of 5-fluorouracil/cisplatin (Group C). In Group A, there was a 60% response rate. Mortality was 70%, with an overall survival rate of 70%, 40%, and 30% at 12, 24, and 60 months, respectively. The mean (SD) survival was 46.7 (15.4) months. In Group B, the response rate was 40%, with an 80% mortality rate and a survival rate of 60% and 20% at 12 and 24 months, respectively. The mean (SD) survival was 17.0 (3.8) months. In Group C, 20% of the responses were observed and the mortality was 90%, with an overall survival rate of 10% at 12 and 24 months and a mean (SD) survival of 7.6 (2.0) months. CONCLUSION: The best response and overall survival rates were achieved in Group A with the NACT scheme of bleomicine.

A remarkable case of cutaneous metastatic breast carcinoma.

We describe a 50-year-old woman with a 5-month history of multiple asymptomatic papulonodular lesions on the left chest area. Biopsy was consistent with cutaneous metastases from a ductal breast carcinoma. No distant metastatic lesions were detected. The patient was referred to the Gynecologic Oncology Department. Treatment included chemotherapy, radiotherapy and surgery. At present the patient is well with no signs of recurrence. This case reports a clinically remarkable cutaneous metastatic breast carcinoma.

[Dysmenorrhea in adolescents and young adults: prevalence, related factors and limitations in daily living]. / Dismenorreia em adolescentes e jovens adultas: prevalência, factores associados e limitações na vida diária.

OBJECTIVE: To determine the prevalence of dysmenorrhea, limitations in daily living and health care use due to menstrual pain. MATERIAL AND METHODS: Observational transversal study of 274 adolescents and young adults (age ≤ 26) who had menstruated in the six months prior to the study, assisted at a Primary Health Care Center. Data were obtained by a 24-item anonymous questionnaire, which included questions about socio-demographic variables, menstrual cycle, presence, duration, severity, treatment and limitations of dysmenorrhea. RESULTS: One hundred and seventy-two (62.8%) subjects experienced menstrual pain. Of these, 65.7% reported having limitations in their daily activities due to dysmenorrhea. The prevalence of limitations in daily living was influenced by the presence of additional symptoms (r=0.331; p <0.001), pain intensity (r=0.281; p <0.001) and pain duration (r=0.172; p=0.027). The most commonly mentioned limitation was anxiety/depression (42.5%). Fourteen of the subjects reported missing school or work due to dysmenorrhea. A total of 48 respondents sought medical help and 135 reported using therapeutic measures to ease their pain. The most common treatments reported for pain treatment included NSAID's (38.5%) and oral pills (37.0%). The existence of additional symptoms (r=0.247; p=0.001) and the intensity of pain (r=0.160; p=0.039) led to the search for health care. CONCLUSIONS: Dysmenorrhea is highly prevalent among this sample of adolescents and young adults and is related to absenteeism. Thus, health care providers should regularly screen for dysmenorrhea and offer appropriate treatment.