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.

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.

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.

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.

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.

Clinical and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Multicenter Retrospective Cohort Study of Tertiary Centers.

BACKGROUND: The term uterine smooth muscle tumor of uncertain malignant potential (STUMP) indicates a rare, equivocal entity between benign leiomyomas and leiomyosarcomas. In the present study, we evaluated a comprehensive range of clinical, surgical, and pathological features in a large multicenter series of patients with STUMP to identify risk factors for recurrence. METHODS: This is a retrospective study performed by collecting consecutive cases diagnosed between January 2000 and December 2020 in five tertiary centers. Associations between STUMP recurrence and clinicopathological characteristics as well as surgical treatment modality were investigated. RESULTS: Eighty-seven patients affected by STUMP were considered. Of them, 18 cases (20.7%) recurred: 11 as leiomyosarcoma (LMS) and 7 as STUMP. The mean time to recurrence was 79 months. We found that fragmentation/morcellation, epithelioid features, high mitotic count, Ki-67 value > 20%, progesterone receptor (PR) < 83%, and p16 diffuse expression were associated with higher risk of recurrence and shorter recurrence-free survival (RFS). Furthermore, morcellation/fragmentation and mitotic count remained independent risk factors for recurrence and shorter RFS after multivariate analysis, while the presence of epithelioid features was an independent risk factor for recurrence only. CONCLUSIONS: Our results suggest that morcellation is associated with risk of recurrence and shorter RFS, thus it should be avoided if a STUMP is suspected preoperatively. Epithelioid features, high proliferation activity, low PR expression, and diffuse p16 expression are also unfavorable prognostic factors, so patients presenting these features should be closely followed up.

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

OBJECTIVE: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma. METHODS: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy. RESULTS: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months. CONCLUSION: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

OBJECTIVES: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS: A multi-institutional retrospective study was conducted within the MITO Group. RESULTS: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.

Fractional CO2 vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors.

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO2 vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO2 laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO2 vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Endometrial thickness in the evaluation of clinical response to medical treatment for deep infiltrating endometriosis: a retrospective study.

PURPOSE: Deep infiltrating endometriosis (DIE) is associated with severe pelvic pain and functional impairment of bowel, urinary, and sexual functions. Though hormone therapy with progestins, either as single agents or combined with estrogens, is effective in managing symptoms, some patients may experience a suboptimal response. Endometrial thickness assessed by transvaginal ultrasound examination, reflecting the overall estrogen stimulation, may correlate with the clinical response to hormonal treatments. METHODS: A retrospective study was carried out on 61 women with DIE affecting the bowel or the recto-vaginal septum, undergoing hormone treatment. The symptoms of patients were evaluated at the baseline and after 12 months of therapy, calculating a global Visual Analogue Scale score (gVAS) encompassing dysmenorrhea, dyspareunia, chronic pelvic pain, dyschezia, abdominal pain and dysuria. Patients were divided into two subgroups using, as a calculated cut-off value, the mean endometrial thickness in our population at 12 months. The change in gVAS score during the 12 months of treatment was then compared between the two groups. RESULTS: Women with a thinner endometrium (< 3.3 mm) showed a better response to treatment in terms of symptoms control as compared to patients with a thicker endometrium (mean gVAS score reduction 9.2 ± 1.3 vs. 5.2 ± 1.3, p = 0.036). The correlation between endometrial thickness and symptomatic response was also confirmed (p = 0.041) on multivariate linear regression analysis including as covariates age, size of lesions of DIE, presence of uterine adenomyosis, ovarian endometriosis and type of medical treatment. CONCLUSION: Endometrial thickness on ultrasound transvaginal examination is correlated with better response rates to hormone therapy in terms of symptoms control. A thinner endometrium, probably resulting from a more efficient suppression of estrogen stimulation, is associated with improved symptoms. These results may aid clinicians in monitoring and tailoring hormonal treatments during follow-up of women with symptomatic DIE.

Vulvovaginal atrophy (VVA) in breast cancer survivors (BCS) is still an unmet medical need: results of an Italian Delphi Panel.

PURPOSE: VVA is a common disease, with approximately 50% of all postmenopausal women having related symptoms. VVA has a significant impact on the personal and sexual lives and on many aspects of women's self-esteem and emotional well-being. It is particularly frequent and severe in patients treated for BC, where it originates significant economic and social costs. Given the lack of published evidence on this subject, a Delphi Panel was carried out to evaluate:The epidemiology of VVA and of its risk-factors/comorbidities in ItalyThe present standard of care and unmet medical needsThe comparison between recent US epidemiological data and the Italian situationThe health resources used in VVA BC The burden of illnessDespite the considerable negative impact on quality of life, a disparity between the high prevalence of this condition and the infrequent clinical diagnosis is documented in medical practice and in surveys. This inaccuracy is thought to be primarily a consequence of patients' unwillingness and/or reluctance to report symptoms in the clinical setting and of health-care professional's difficulty in approaching this sensitive topic during routine consultations. METHODS: A Delphi Panel methodology was used: a first round of written questionnaires, followed by a plenary meeting with a facilitator and by two additional rounds of telephone interviews. RESULTS: The prevalence of the condition in Italy can be estimated in 115,000 cases out of 380,000 BC survivors. The Panel confirmed that the epidemiological findings of a recent pharmacoeconomic analysis of a US claims database can be applied to Italian patient population. The Panel confirmed also an estimate of 4.25 additional cases/100/yr of UTI (urinary tract infection) in VVA BC patients (vs. a non-VVA-matched population), of 3.68 additional cases of vulvovaginitis, of 6.97 cases of climacteric symptoms, and of 3.64 cases of bone and joint disorders. As far as the resource use is concerned, in the VVA BC populations, 33.4 additional gynecological visits/100/year can be expected, along with 22.8 additional cancer screenings, 7.07 additional outpatient visits and 5.04 screenings for HPV. CONCLUSIONS: Even in Italy, a diagnosis of VVA, especially in a BC population, is associated with a relevant increase in the burden of illness and social costs, compared to a control population matched for age without VVA. This is due essentially to an increase in comorbidities and resource utilization with the consequence that an adequate treatment could reduce the impact of the condition.

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines.

Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

Predictors of response after a second attempt of pharmacological labor induction: a retrospective study.

PURPOSE: The aim of our study was to assess the outcomes of a prolonged induction carried out with a second sequential cycle of pharmacological stimulation after unsatisfactory response to a first attempt, and to highlight variables correlated with higher response rates. METHODS: A retrospective study was carried out on 157 women who underwent a two-step labor induction by vaginal prostaglandins followed by a second cycle of prostaglandins or intravenous oxytocin. Outcomes assessed were mode of delivery and maternal and neonatal morbidity. Main variables of pregnancy and delivery were collected to identify factors predicting the mode of delivery. RESULTS: Among 157 patients, 63 (40.1%) achieved a vaginal delivery, whereas 94 (59.9%) underwent Cesarean section, 9 women (5.7%) had postpartum hemorrhage; in 2 cases (1.3%), an Apgar score < 7 at 5 min from birth was reported. Higher risk of Cesarean section was observed with advanced maternal age (OR 1.13 for additional year, CI 1.04-1.22) and nulliparity (OR 8.84, CI 2.69-29.06), whereas the response rates were better in carriers of group B streptococcus colonization (OR 0.38, CI 0.17-0.84) and in women with favorable cervical status after the first stimulation (OR 0.81 for additional point of Bishop score, CI 0.70-0.94). CONCLUSION: Labor induction with two cycles of pharmacological stimulation is a procedure with fairly good success rates and a low risk of maternal and neonatal complications. Factors predicting its success encompass younger age, parity, a positive recto-vaginal swab for group B streptococcus and a favorable cervix following the first cycle of stimulation.

ERα upregulates the expression of long non-coding RNA LINC00472 which suppresses the phosphorylation of NF-κB in breast cancer.

PURPOSE: Low expression of long intergenic non-coding RNA LINC00472 in breast cancer is associated with aggressive tumors and unfavorable disease outcomes in multiple clinical datasets, but the reasons for these associations were unknown. METHODS: To study the mechanisms underlying the lncRNA's connection to breast cancer, we investigated the molecular targets and regulation of LINC00472 in breast cancer cells, and analyzed relevant molecular features in relation to patient survival. Gene expression profiles of breast cancer cells overexpressing LINC00472 were analyzed for its regulatory pathways and downstream targets. Effects of LINC00472 overexpression on cell behaviors were evaluated in vitro and in vivo. Meta-analysis was performed using online datasets and our own study. RESULTS: Analysis of LINC00472 transcriptome revealed ERα upregulation of LINC00472 expression, and an ERα-binding site in the LINC00472 promoter was identified. Evaluation of LINC00472 overexpression also indicated a possible link between LINC00472 and NF-κB. Cell experiments confirmed that LINC00472 suppressed the phosphorylation of p65 and IκBα through binding to IKKß, inhibiting its phosphorylation. High LINC00472 expression inhibited tumor growth both in vitro and in vivo and suppressed aggressive tumor cell behaviors in vitro. Suppressing LINC00472 expression in ER-positive tumor cells increased cell aggressive behaviors. Tamoxifen treatment of ER-positive cells inhibited ERα and LINC00472 expression and increased p65 and IκBα phosphorylation. Meta-analysis showed that LINC00472 expression were higher in ER-positive than ER-negative tumors and that high expression was associated with better disease outcomes in ER-positive patients. CONCLUSIONS: The study demonstrates that ERα upregulates LINC00472 which suppresses the phosphorylation of NF-κB, and suggests that endocrine treatment may lower LINC00472 and increase NF-κB activities, leading to tumor progression and disease recurrence.

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy.

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women's Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT's effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65-0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07-10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56-0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42-0.87). Data about ovarian and cervical cancer are still controversial.

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival.

PURPOSE: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a prognostic marker for the metastasis of early-stage non-small cell lung cancer (NSCLCs). We studied MALAT1 expression in breast cancer in relation to disease features and patient survival. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure MALAT1 expression in tumor samples of 509 breast cancer patients. Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between MALAT1 expression and breast cancer survival using the Cox proportional hazards regression model, and the analysis was adjusted for age at surgery, tumor grade, disease stage, and hormone receptor status. Meta-analysis of multiple microarray datasets from online databases and our own study was performed to evaluate the association of MALAT1 with breast cancer survival. RESULTS: Patients with low-grade or ER-positive tumors had higher expression of MALAT1 compared to those with high-grade (p = 0.013) or ER-negative (p = 0.0002) tumors. Patients with PR-positive tumors also had higher MALAT1 expression than those with PR-negative tumors (p < 0.0001). In patients with positive hormone receptors or low tumor grade, tumors with high MALAT1 expression were more likely to recur. Survival analysis showed that patients with high expression of MALAT1 had a twofold increase in risk of relapse (p = 0.0083) compared to those with low expression. This association remained significant after adjustment for age at surgery, disease stage, tumor grade, and hormone receptor status. Meta-analysis showed that high MALAT1 expression was associated with poor relapse-free survival in patients with hormone receptor-positive tumors (HR 1.44, 95% CI 1.08-1.92). CONCLUSIONS: High expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

Unexpected uterine leiomyosarcoma in a woman with multiple myomas treated with ulipristal acetate: case report and literature review.

Ulipristal acetate (UPA) has been recognized as an alternative strategy to surgery in the management of symptomatic women with uterine fibroids. We present a case report on a woman with hereditary fibrinogen deficiency exclusively treated with UPA for myoma-related menorrhagia and abdominal pain, who subsequently underwent a hysterectomy because of clinical worsening. A FIGO IB uterine leiomyosarcoma was found among multiple myomas. A review of the literature found two other cases of uterine leiomyosarcoma in patients treated with UPA: clinical data are reported. The aim of this case report is to increase clinicians' awareness that, although rare, leiomyosarcoma can develop in a uterus with multiple myomas and no reliable diagnostic tools exist yet. Thus, a clinical and instrumental careful reevaluation and patient counseling should be a priority when planning to repeat UPA treatment cycles.