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Paraneoplastic pemphigus is an autoimmune skin and mucosal disorder, rarely associated with solid malignancies, with devastating impact.

Anastasios Kyriazoglou, 1 Konstantinos Koutsoukos, 1 Flora Zagouri, 1 Michalis Liontos, 1 Efthimios Dimitriadis, 2 Dina Tiniakos, 3, 4 Meletios Athanasios Dimopoulos 1 1Department of Clinical Therapeutics, General Hospital Alexandra, Athens, Greece; 2Department of Genetics, Agios Savvas Hospital, Athens, Greece; 3Department of Pathology Aretaion Hospital, National & Kapodistrian University of Athens, Athens, Greece; 4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UKCorrespondence: Anastasios Kyriazoglou Vasilisis Sofias 80, Athens 11528, GreeceTel +302132162545Fax +302132162511Email tassoskyr@gmail.comAbstract: Epithelioid hemangioendothelioma (EHE) is a rare vascular malignant tumor with indolent course. Liver transplantation for local disease is the treatment of choice. In the metastatic setting there is no consensus regarding the appropriate systemic treatment. We present two cases of metastatic hepatic epithelioid hemangioendothelioma (hEHE) treated with the combination of Doxorubicin and Olaratumab. Both patients showed Stable Disease (SD) as a response, after the completion of six cycles of this combination therapy.Keywords: Olaratumab and Doxorubicin, metastatic hepatic epithelioid hemangioendothelioma, 1st line treatment

Bromodomain and extraterminal domain (BET) proteins are epigenetic molecules that regulate the expression of multiple genes involved in carcinogenesis. Breast cancer is an heterogenous disease emerging from aberrant gene expression and epigenetic alteration patterns. Amplification or overexpression of BET proteins has been identified in breast tumors highlighting their clinical significance. Development of BET inhibitors that disrupt BET protein binding to acetylated lysine residues of chromatin and suppress transcription of various oncogenes has shown promising results in breast cancer cells and xenograft models. Currently, Phase I/II clinical trials explore safety and efficacy of BET inhibitors in solid tumors and breast cancer. Treatment-emergent toxicities have been reported, including thrombocytopenia and gastrointestinal disorders. Preliminary results demonstrated greater response rates to BET inhibitors in combination with already approved anticancer agents. Consistently, BET inhibition sensitized breast tumors to chemotherapy drugs, hormone therapy and PI3K inhibitors in vitro. This article aims to review all existing preclinical and clinical evidence regarding BET inhibitors in breast cancer. • BET proteins are epigenetic readers that regulate transcription of multiple cancer-associated genes. • BET inhibitors attenuate BET protein association to chromatin suppressing oncogene pathways. • Preclinical studies have shown promising efficacy of BET inhibitors in breast cancer murine xenografts and cell lines. • BET inhibitors provided an additive effect to widely used anticancer agents, including chemotherapy drugs, hormone therapy and tyrosine kinase inhibitors. • Ongoing Phase I/II trials revealed a potent BETi antitumor efficacy and safety limitations due to hematologic and gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

Background: The emphasis on aesthetic outcomes and quality of life after breast cancer surgery has motivated breast surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of these techniques. This systematic review aims to assess oncological and cosmetic outcomes of OPS. Methods: After a strict selection process with precise inclusion and exclusion criteria, oncologic and aesthetic outcomes of oncoplastic surgery were searched, using the MEDLINE database up to September 30th, 2017. Available published literature was classified in levels of evidence. After a thorough screening process, only studies with the best level of evidence were included on selection. Systematic reviews and meta-analyses were not included for methodological reasons. Results: Titles and abstracts of 2.854 citations were identified and after screening 15 prospective studies including 1.391 patients were reviewed and scored in detail. Local relapse was found in 2.8% of cases with a wide range of follow-up (from 6 to 74 months). Close margins were retrieved in 11% of cases and positive margins in 9.4% of cases. Mastectomy was implemented in 6.9% of breast cancer patients to whom OPS was performed. Good cosmetic outcomes were detected in 90.2% of patients undergoing OPS, leaving open issues for who should perform cosmetic evaluation and which method should be used. Conclusion: Tumor margins, mastectomy rates, and cosmetic outcomes of OPS have to be further improved by standardizing various aspects of OPS. Research efforts should focus on level I evidence assessing both oncological and aesthetic outcomes of OPS and survival rates. [ABSTRACT FROM AUTHOR]

The article discusses the learning curve of breast lesion excision system: Balancing patient's safety and surgical training. Topics include operative time for removing the sample and time for clip were significantly decreased from 2014 to 2015 for doctors of all levels of experience jointly; and the learning curve shows that doctors can learn the procedure through a "live" training model without compromise in the quality of patient care..

Background:Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce.Methods:In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated.Results:Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted.Conclusion:Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients. [ABSTRACT FROM AUTHOR]

Background:The mesenchymal-epithelial transition (MET) pathway is frequently altered in tumours. The purpose of our study was to determine the prognostic value of tumour MET expression levels in patients with triple-negative breast cancer (TNBC), in order to strengthen the rationale for targeted therapy of TNBC using MET inhibitors.Methods:We determined expression of MET in formalin-fixed paraffin-embedded surgical specimens of TNBC by immunohistochemistry. Recurrence-free and overall survival was analysed with Cox models adjusted for clinical and pathological factors.Results:Immunostaining for MET was classified as high in 89 of 170 (52%) tumours. MET expression was more frequently observed in G3 carcinomas (P=0.02) but was not significantly associated to any of the other clinical or pathological parameters. High MET expression predicted shorter survival of the patients. Multivariate Cox proportional hazards regression analyses identified MET to be an independent prognostic factor for recurrence (adjusted hazard ratio (HR) for recurrence 3.43; 95% confidence interval (CI) 1.65-7.12; P=0.001) and death (adjusted HR for death 3.74; 95% CI 1.65-8.46; P=0.002).Conclusion:These results provide further evidence that the MET pathway could be exploited as a target for TNBC. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer is the most common solid carcinoma diagnosed during pregnancy; obviously, pregnancy adds complexity to treatment recommendations. We synthesized all available data and evaluated the efficacy and safety of the administration of platinum derivatives during pregnancy in cervical cancer.Data Sources: Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases for the period up to September 7, 2012; the algorithm comprised a predefined combination of the terms "cervical," "cancer," "cisplatin," carboplatin," and "pregnancy."Methods Of Study Selection: Two investigators, working independently, searched the literature and extracted data from all studies that examined the efficacy and safety of platinum derivatives administered during pregnancy in cervical cancer. All cases in which therapeutic abortion was scheduled were excluded. Moreover, quantitative synthesis of the published articles was performed.Tabulation, Integration, and Results: Overall, 24 studies (48 pregnancies, 48 newborns [one twin pregnancy and one miscarriage]) were eligible. In relation to cisplatin, 47 pregnancies were identified, whereas regarding carboplatin administration, only one pregnancy was retrieved. Cisplatin was administered either as monotherapy or combined with bleomycin, 5-fluorouracil, paclitaxel, vincristine, and bleomycin, whereas carboplatin was given in combination with paclitaxel. In most cases (67.4%), a completely healthy neonate was born; all children were healthy with a median follow-up of 12.5 months. The mean delivery weight of newborns was 2,213 g. Complete and partial response was achieved in 10% and 63.4% of patients with cervical cancer, respectively, whereas stabilization and progression of the disease occurred in 23.3% and 3.3% of women in the case group. In the majority of women in the case group, chemotherapy was well tolerated. The median progression-free survival was 48.5 months.Conclusion: Cisplatin may play a significant role in the management of patients with cervical cancer during the second and third trimesters. [ABSTRACT FROM AUTHOR]

The article examines the role of molecular markings on the development of epithelial ovarian cancer. It presents an analysis on the potential usefulness and function of molecular markers, which include the ras proteins, endothelin, and metalloproteinase, in ovarian cancer. It also suggests the need for accurate and efficient prognosis of cancer and the awareness of the physicians in molecular biology to make them capable treating every patient according to their risk factors and tumour markers.

The article reports on the disentanglement of different adjuvant modes of advanced stage uterine sarcomas, especially its pathological subtype. It states that carcinocarcomas, leiomyosarcomas (LMS), and endometrial stromal sarcoma (ESS) are most common pathological types of uterine sarcomas. It mentions the prognosis, molecular markers, surgery, and therapies of these pathological types. It suggests that patients diagnosed with uterine sarcoma should be encouraged to enter clinical tests.

Background: A matter of substantial concern regarding all needle biopsy techniques is seeding along the biopsy needle tract. Purpose: To assess cell seeding along the needle tract of vacuum-assisted breast biopsy (VABB). Material and Methods: The study included 21 patients with ductal carcinoma in situ (DCIS) and 10 patients with invasive ductal carcinoma (IDC) diagnosed by VABB for nonpalpable mammographic lesions. VABB (11G, on a Fischer table) was performed, and the duration of the procedure was measured. After surgery, the whole needle tract was embedded in paraffin blocks, stained with hematoxylin-eosin, and examined by a pathologist. Results: Cases with dissemination of cancer cells in the needle tract were not observed (one-sided 97.5% CI 0-10.0%). In 2/31 (6.5%) cases (95% CI 0.8-21.4%), benign epithelial cell displacement was observed, and the duration of VABB was significantly longer in these two cases (52.5±3.5 min vs. 42.0±4.4 min for cases without benign cell displacement; P = 0.018, Mann-Whitney-Wilcoxon test for independent samples). Conclusion: No displacement of malignant cells within the 11G needle tract was documented. Benign cell displacement was associated with longer VABB duration. The phenomenon of tumor cell dissemination along the needle tract is of questionable clinical significance when the treatment guidelines are followed. [ABSTRACT FROM AUTHOR]

The article presents case studies of a 36-year-old woman who underwent laparascopic surgery due to uterine leimyoma and a 47-year-old woman who presented with lower abdominal pain and was diagnosed with a well circumscribed intramural tumor. Both patients showed peritomeal dissemination after laparoscopic excision of endometrial stromal tumors. The article also discusses the alternative treatment of uterine leiomyomas and the implant of endometrial stromal tissue into the abdominal cavity.

In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; P = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data. Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts. Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the Table). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were < 10.0 events per 100 person-months of exposure during any period. Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase. [ABSTRACT FROM AUTHOR]

Background: Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).Methods: Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC.Results: Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC.Conclusion: The above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to vacuum-assisted breast biopsy.

A letter to the editor is presented which inquires about the role of vacuum-assisted breast biopsy (VABB) in sentinel lymph node assessment.

Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast.~Background~Background~Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.~Methods~Methods~Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 +/- 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 +/- 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 +/- 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 +/- 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 +/- 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 +/- 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage.~Results~Results~Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]