A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

Induction of labor with repeated prostaglandin administration after failure of dinoprostone vaginal insert: a retrospective study comparing dinoprostone and misoprostol.

BACKGROUND: Induction of labor in women with unfavorable cervix can be started with cervical ripening by dinoprostone vaginal insert. In cases of unsuccessful response, management is unclear: a possible option is a repeated induction with prostaglandins. The aim of this study was to assess the results of a second induction by either dinoprostone or misoprostol, comparing those treatments. METHODS: A retrospective analysis was carried out on a cohort of 109 women with unsuccesful response to a first attempt of induction with dinoprostone vaginal insert, who required a second stimulation by either dinoprostone vaginal gel (56 patients) or oral misoprostol (53 patients). The outcomes assessed where the rates of active labor and vaginal delivery, and secondarily maternal and perinatal adverse events. RESULTS: Overall 70.6% of patients reached active labor and 62.4% had a vaginal delivery; the efficacy of the double induction was similar for dinoprostone vaginal gel and oral misoprostol, with active labor in 69.6% and 71.7% (P=0.83), and vaginal delivery in 62.5% and 62.3% of patients (P=0.99) respectively. The incidence of adverse events was low, with no perinatal complications and similar rates of maternal complications, notably major post-partum hemorrhage in 1.8% and 3.8% of patients (P=0.61) for dinoprostone and misoprostol respectively. CONCLUSIONS: Dinoprostone vaginal gel and oral misoprostol as a second cycle of induction appear to be both effective in achieving active labor and vaginal delivery after failure of dinoprostone vaginal insert, without a significant rate of adverse events.

Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

Clinical, Pathological, and Prognostic Features of Male Breast Cancer: A Multicenter Study.

Male breast cancer (BC) represents less than 1% of male tumors. Little is known about male BC characteristics, management, and survival, with many studies based on a small number of cases. Consequently, the treatment of male BC lacks specific guidelines. The aims of the study are to compare male and female breast cancer (FBC) in terms of cancer clinical and anatomopathological features and treatment approach, and to identify differences between male BC and FBC in terms of survival. Patients and methods: Data from 2006 to 2018 were retrospectively acquired. Amounts of 49 males and 680 postmenopausal females with primary non-metastatic BC who underwent breast surgery at Mauriziano Hospital or IRCCS Candiolo (TO-Italy) were included. The mean age at diagnosis for male BC was 68.6 years, and males presented a smaller tumor size than women (p < 0.05) at diagnosis. Most male BC patients received adjuvant endocrine therapy (AET) with tamoxifen (73.5%). AET drop-out rate due to side effects was 16.3% for males compared to 7.6% for women (p = 0.04). Comparing FBC and male BC, no differences have been identified in terms of DFS and OS, with a similar 10-year-relapse rate (12% male BC vs. 12.4% FBC). Propensity Score Matching by age, nodal status, pT, and molecular subtype had been performed and no differences in OS and DFS were seen between male BC and FBC. In conclusion, male BC and FBC have similar prognostic factors and survival outcomes. The drop-out rate of AET was higher in males, and side effects were the main reason for drug discontinuation.

Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients.

Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, ß-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC.

Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.

BRCA1/2 mutations account for 5 to 10% of breast and 15% of ovarian cancers. Various guidelines on BRCA1/2 genetic counseling and testing have been issued, and the criteria have evolved over the years. Oncogenetic counseling aims to inform patients about the possibility and implications of undergoing predictive testing and risk management programs. We analyzed a cohort of 50 subjects with a previous personal history of breast or ovarian cancer who had not been tested for BRCA1/2 mutations at the time of diagnosis but were found eligible according to the most recent guidelines. All patients were offered pre-test oncogenetic counseling and BRCA1/2 genetic testing. The mean time from cancer diagnosis to genetic counseling was over 10 years. We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. The offer of BRCA testing was well accepted by our study population, despite the many years since the cancer diagnosis. With the perspective of further broadening the access criteria to genetic testing, it is important to understand how to best approach pre-test counseling in long-surviving patients with a previous diagnosis of cancer.

Development and clinical application of a tool to identify frailty in elderly patients with gynecological cancers.

OBJECTIVE: Frailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have received unanimous consent or been specifically designed for women with gynecological malignancies.This study's aim was to develop a clinical application of a screening tool to identify frail patients >70 years old diagnosed with either ovarian or endometrial cancers. METHODS: A 20 item questionnaire was developed and administered to the cohort before surgery or neoadjuvant chemotherapy. A cut-off for frailty definition was determined by analyzing the correlation of questionnaire scores with the completion of treatments. The association between frailty and treatment related complications was assessed using a Chi-squared test for categorical variables and a t-test for continuous variables. RESULTS: Our study included 100 patients, 50% diagnosed with endometrial cancer and 50% with ovarian cancer. A questionnaire score of 4 was the best cut-off for frailty definition (sensitivity 77%, specificity 100%). Surgical grade III and grade IV complications were observed only in frail patients (p=0.01) and hospitalization was significantly longer in frail women affected by ovarian cancer (p=0.01). Frail patients were more exposed to chemotherapy administration delay (p=0.0005), treatment discontinuation (p=0.001) and hematological toxicities, especially anemia ≥grade 2 (p=0.009) and thrombocytopenia any grade (p=0.0001). CONCLUSION: With a cut-off score of 4, our tool can identify frail patients with significantly higher incidence of grade III-IV postoperative complications, length of stay, medical treatment discontinuation rates and hematological toxicities.

Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience.

BACKGROUND: There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status. METHODOLOGY: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. RESULTS: A total of 312 patients treated between 2010 and 2022 in four high-volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. In total, 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31-91) years. Among patients with localized disease, median RFS was 100.0 months (95% CI 59.4-140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p = 0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p = 0.039). In patients receiving platinum-based chemotherapy, no statistically significant differences in PFS (p = 0.21) or OS (p = 0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. CONCLUSIONS: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

BACKGROUND: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). METHODS: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. RESULTS: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. CONCLUSIONS: Ki67 at diagnosis did not discriminate responders to PARPi.

Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. METHODS: A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. RESULTS: Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. CONCLUSIONS: AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient-physician communication and a good-quality care network.

Bone modifying agents in postmenopausal breast cancer patients treated with aromatase inhibitors: beyond bone protection?

Estrogen-receptor positive tumours represent the majority of breast cancers in postmenopausal women. Adjuvant endocrine therapy with aromatase inhibitors (AIs), continued for up to 10 years in high-risk patients, reduces by 40% the risk of recurrence. However, this therapy, among other side effects, is burdened with a higher incidence of osteoporotic bone fractures. To date, both bisphosphonates and denosumab are recognized as first-line drugs in the primary prevention of osteoporotic fractures in patients treated with AIs. They have demonstrated their effectiveness in increasing bone mineral density and in reducing the incidence of fractures, but they have also been shown to improve disease free survival (DFS).

Straining to void at preoperative urodynamic study as a risk factor for prolapse recurrence after surgery.

OBJECTIVES: Straining to void is the need to make a muscular effort in order to initiate, maintain or improve the urinary stream, through an increase in abdominal pressure. This pattern of bladder emptying is frequently observed in women with pelvic organ prolapse causing urinary obstruction, to overcome the increased resistance to urine flow. However, frequent increases in abdominal pressure are a risk factor for developing pelvic organ prolapse, and might play a role in its recurrence after surgery. The aim of this study was to investigate the role of straining identified at urodynamic study in prolapse recurrence after surgical repair. STUDY DESIGN: This was a retrospective study on women submitted to prolapse repair by vaginal hysterectomy with modified McCall culdoplasty and anterior colporraphy. All patients underwent a preoperative urodynamic evaluation including a pressure-flow study performed after prolapse reduction by means of a vaginal pessary; straining was defined by a simultaneous and similar increase in intravesical and abdominal pressures of at least 10 cmH2O over the baseline during bladder emptying, corresponding to intermittent peaks of urine flow. Patients were divided into two groups according to the presence or absence of straining, and they were compared for surgical results at 12 months and for the rate of anterior or central recurrence over time. RESULTS: Women with straining (n = 16), compared to women with normal voiding (n = 43), showed a higher risk of anterior recurrence over time at Kaplan-Meier curves, for both stage II (p = 0.02) and stage III prolapse (p = 0.02). No difference was seen for central recurrence during the follow up period. POP-Q staging at 12 months was similar for the two groups, except for the location of the Aa point which was significantly better for women without straining (-1.6 ± 0.1 cm vs -0.8 ± 0.3 cm, p = 0.03). CONCLUSIONS: Straining to void identified in preoperative urodynamic study seems to increase the risk of anterior recurrence after surgical repair of pelvic organ prolapse.

Prescribing pattern of anticoagulants in patients with cancer associated thrombosis: Results of a survey among MITO group and AIOM society.

INTRODUCTION: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs). METHODS: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members. RESULTS: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively. CONCLUSION: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them.

Clinical, Sonographic, and Hysteroscopic Features of Endometrial Carcinoma Diagnosed after Hysterectomy in Patients with a Preoperative Diagnosis of Atypical Hyperplasia: A Single-Center Retrospective Study.

BACKGROUND: atypical endometrial hyperplasia (AEH) is a precancerous condition implying a high risk of concurrent endometrial cancer (EC), which might be occult and only diagnosed at postoperative histopathological examination after hysterectomy. Our study aimed to investigate potential differences in preoperative clinical, sonographic, and hysteroscopic characteristics in patients with AEH and postoperative diagnosis of EC. METHODS: a retrospective single-center study was carried out on a case series of 80 women with AEH undergoing diagnostic workup, including ultrasonography and hysteroscopy, with subsequent hysterectomy. Women with AEH confirmed at the histopathological examination were compared with patients with a postoperative diagnosis of EC. RESULTS: in our population, EC was diagnosed in 53 women, whereas the preoperative diagnosis of AEH was confirmed in 27 cases. At ultrasonography, women with occult EC showed greater endometrial thickness (20.3 mm vs. 10.3 mm, p 0.001) and size of the endocavitary lesion (maximum diameter 25.2 mm vs. 10.6 mm, p 0.001), and a higher prevalence of irregular endometrial-myometrial junction (40.5% vs. 6.7%, p 0.022) and endouterine vascularization at color Doppler (64.2% vs. 34.6%, p 0.017). At hysteroscopy, patients with occult EC showed a higher prevalence of necrosis (44.2% vs. 4.2%, p 0.001) and atypical vessels (70.6% vs. 33.3%, p 0.003), whereas true AEH mainly presented as a protruding intracavitary lesion (77.8% vs. 50.9%, p 0.029). In EC, subjective assessment by the operator was more frequently indicative of cancer (80.0% vs. 12.5%). No difference was found for clinical variables. CONCLUSIONS: occult EC in AEH may exhibit some differences in ultrasonographic and hysteroscopic patterns of presentation compared with real AEH, which could prompt a more significant suspect for the possible presence of concurrent EC at preoperative diagnostic workup.

The "Sandwich" Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate-High- and High-Risk Endometrial Cancer.

(1) Background: In intermediate-high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The "sandwich" schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the "sandwich" schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate-high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin-paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The "sandwich" schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate-high- and high-risk EC.

FOXA1 in Breast Cancer: A Luminal Marker with Promising Prognostic and Predictive Impact.

The present review focuses on the function of the forkhead protein FOXA1 in breast cancer (BC) in relation to steroid hormone receptors. We explored the currently available analytic approaches for FOXA1 assessment both at gene and protein levels, comparing the differences between the available techniques used for its diagnostic assessment. In addition, we elaborated on data regarding the prognostic and predictive role of this marker in BC based on several studies that evaluated its expression in relation to the outcome and/or response to therapy. FOXA1, similar to the androgen receptor (AR), may have a dual role in BC according to hormonal status. In luminal cancers, its expression contributes to a better prognosis, while in triple-negative breast cancers (TNBC), it implies an adverse outcome. Consequently, we observed that FOXA1-positive expression in a neoadjuvant setting may predict a lack of response in luminal BC as opposed to TNBC, in which FOXA1 allegedly increases its chemosensitivity. In conclusion, considering its accessible and convenient identification by immunohistochemistry, its important impact on prognosis, and its suitability to identify patients with different responses to chemotherapy, we propose that FOXA1 could be tested in routine diagnostics as an additional prognostic and predictive marker in BC.

Immunohistochemical Markers and TILs Evaluation for Endometrial Carcinoma.

OBJECTIVE: The molecular classification for endometrial cancer (EC) introduced by The Cancer Genome Atlas Research Network (TCGA) and the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) proved the existence of four molecular prognostic subtypes; however, both classifications require costly technology. We suggest a prognostic model for EC based on immunohistochemistry (IHC) and tumor-infiltrating lymphocytes (TILs). STUDY DESIGN: One hundred patients were included. We retrospectively investigated IHC prognostic parameters: mismatch repair (MMR)-deficient tumors, p53 mutation status, progesterone receptors (PgRs), and estrogen receptors (ERs). We further evaluated TILs. These parameters were related to the clinical and morphological features and to the outcome. RESULTS: We classified tumors into three groups (IHC analysis): MMR-deficient, p53-mutated, p53 wild-type. MMR-deficient tumors had a good prognosis, p53 wild-type tumors an intermediate one, and p53-mutated tumors had the poorest outcomes. Disease-free (DFS) and overall survival (OS) were significantly better among PgR+ tumors (respectively p = 0.011 and p = 0.001) and PgR expression is an independent prognostic factor for a better DFS frommultivariate analysis (OR = 0.3; CI: 0.1-0.9; p = 0.03).No significant correlation was observed between DFS and TILs. However, among MMR-deficient tumors, the mean value of TILs was higher than among the other tumors(111 versus 71, p = 0.01) Conclusions: The prognostic model based on IHC markers could potentially be a valid and applicable alternative to the TCGA one. The PgR determination could represent an additional prognostic factor for EC.

Immunonutrition in ovarian cancer: clinical and immunological impact?

OBJECTIVE: Malnutrition is frequent in ovarian cancer (OC) patients and may compromise post-operative outcomes. The aim of this study is to evaluate the impact of pre-operative immunonutrition on the surgical outcome of OC patients, and on their nutritional, inflammatory and peripheral blood immune status. METHODS: A prospective study was performed between September 2016 and April 2020. Immune-enhancing enteral nutrition was administered to 42 patients before surgery according to their nutritional status assessed by the Malnutritional Universal Screening Tool. Biochemical and hematological monitoring was performed before and after immunonutrition. Post-operative outcomes were assessed and compared with those of a similar group of patients treated without nutritional support. RESULTS: Of the 42 immune-nourished patients, 23 (54.8%) had a low, 11 (26.2%) an intermediate and 8 (19%) a high risk of malnutrition. After the immunonutritional intake, significant variations of prealbumin, creatinine and white blood cells were detected. All T cell populations had an increasing trend, in particular CD3+ T lymphocytes (p=0.020), CD3+CD8+ cytotoxic T lymphocytes (p=0.046) and lymphocyte with HLA-DR expression (p=0.012). The rate of grade II-III post-operative complications was lower (21.4% vs. 42.9%, p=0.035) and the time of hospitalization was shorter (7.5 vs. 9.2, p=0.009) in the immune-nourished group. CONCLUSION: Pre-operative immunonutrition improves the surgical outcome of OC patients. After immunonutrition, an increase of CD3+CD8+ cytotoxic T lymphocytes was observed.