BACKGROUND: Male breast cancer accounts for 1% of all breast cancers. Its low frequency leads to a lack of awareness, resulting in significant diagnostic delays. Additionally, this limits the available evidence, which primarily uses diagnostic-therapeutic algorithms based on women.
OBJECTIVE: To analyze the prevalence, clinical presentation, anatomical and pathological characteristics, and prognosis of male breast cancer using one of the largest series available. Secondarily, to compare our data with studies conducted in women.
METHODS: A multicenter, observational, descriptive, retrospective study was conducted in the autonomous community of Aragon, Spain, from 1995 to 2022 including men with a pathological diagnosis of breast cancer.
RESULTS: A total of 148 patients were included, with a prevalence of 1%. The most common clinical presentation was a palpable retroareolar mass. Invasive ductal carcinoma was the most frequent type (88.89%), and luminal B was the predominant subtype (47.76%). Surgery was the most utilized treatment; mastectomy was performed in 90.34% and AL in 46.89%. At diagnosis, 52.46% had extramammary involvement. The recurrence rate was 24.1%, and the mortality attributed to the disease was 14.6%.
CONCLUSIONS: There is a high rate of metastatic involvement at diagnosis, a high percentage of mutilating surgeries, and a high number of recurrences compared to available studies on males. Additionally, a worse prognosis is observed compared to breast cancer in women, despite these tumors having a less aggressive molecular subtype. These findings highlight the importance of conducting studies focused on men to develop specific protocols.

The gonadotropin treatment of infertile men may improve spermatogenesis and lead to sperm cell production, however, only a small fraction of treated patients positively responds to such therapy. To identify individual treatment prognostic biomarkers associated with responsiveness to gonadotropins, we compared the gene expression profiles of testicular oligobiopsies from 3 patients with non-obstructive azoospermia (NOA) who positively responded to therapy with a combination of human chorionic gonadotropin and recombinant follicle-stimulating hormone (hCG/rFSH) to those of 3 non-responders. We used Affymetrix Human Gene 1.0 ST microarrays. The results of the microarray evaluation were validated by the qPCR technique while gene variants of the HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) were subsequently sequenced. In our microarrays, we have identified most significantly 5 transcripts with different expression levels in responders versus non-responders groups. Our interest has been primarily focused on the transcript associated with the HLA-DQB1 gene. Because the expression of this gene was up-regulated in the non-responding patients and only patients with heterozygotic alleles of HLA-DQB1 turned out to be positive to gonadotropin therapy, we suggest that this gene may be a biomarker of potential significance for the gonadotropin treatment of male infertility. We also compared the testicular gene expression profile in one individual before and after gonadotropin treatment. In the re-biopsied sample, we have identified over 600 genes that showed differences in testicular expression; some of these genes are critical for spermiogenesis. Thus, we documented that the applied gonadotropins successfully stimulated the spermatogenetic wave in patients with NOA.

OBJECTIVE: Patients bearing estrogen receptor (ER)α-negative breast cancer tumors confront poor prognosis and are typically unresponsive to hormone therapy. Previous studies have shown that calcitriol, the active vitamin D metabolite, can induce ERα expression in ERα-negative cells. EB1089, a calcitriol analog with reduced calcemic effects, exhibits greater potency than calcitriol in inhibiting cancer cell growth. However, the impact of EB1089 on ERα expression in triple-negative breast cancer (TNBC) cells remains unexplored. This study aims to investigate whether EB1089 could induce functional ERα expression in TNBC cell lines, potentially enabling the antiproliferative effects of antiestrogens.
METHODS: TNBC cell lines HCC1806 and HCC1937 were treated with EB1089, and ERα expression was analyzed using real-time PCR and Western blots. The transcriptional activity of induced ERα was evaluated through a luciferase reporter assay. The antiproliferative effects of tamoxifen and fulvestrant antiestrogens were assessed using the sulforhodamine B assay in the EB1089-treated cells.
RESULTS: Our findings indicated that EB1089 significantly induced ERα mRNA and protein expression in TNBC cells. Moreover, EB1089-induced ERα exhibited transcriptional activity and effectively restored the inhibitory effects of antiestrogens, thereby suppressing cell proliferation in TNBC cells.
CONCLUSIONS: EB1089 induced the expression of functional ERα in TNBC cells, restoring the antiproliferative effects of antiestrogens. These results highlight the potential of using EB1089 as a promising strategy for re-establishment of the antiproliferative effect of antiestrogens as a possible management for TNBC. This research lays the foundation for potential advancements in TNBC treatment, offering new avenues for targeted and effective interventions.

OBJECTIVE: Hormone therapy (HT) can relieve symptoms of menopause and treat chronic diseases. Its effectiveness in treating psychological symptoms is still debated. Several progestins can be used in HT, but their effects on mood, in particular depressive symptoms, is still unclear. This systematic review evaluates the evidence from randomized clinical trials with postmenopausal women on the effect of adjunctive progestins on symptoms of depression assessed by validated questionnaires. The primary aim was to evaluate scores on the Center for Epidemiologic Studies Depression Scale (CESD). The secondary aim was to assess scores on the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAMD), and the Zung Self-Rating Depression Scale (SDS).
METHODS: A systematic review and meta-analysis were conducted to identify the most reliable evidence of the effects of progestin on depression to inform decision-making. A PICO- and PRISMA-based framework was established to formulate explicit and reasoned recommendations. The pre-/post-treatment effect was evaluated using standardized mean change (SMC).
RESULTS: We selected and analyzed 16 randomized clinical trials qualitatively and 12 studies quantitatively out of 9320 items identified. Most of the studies used medroxyprogesterone acetate as progestin. The results indicate that depressive symptoms do not increase with the addition of a progestin to estrogen HT. Depressive symptoms improved over time in the progestins-estrogen HT group, independent of progestin type (SMC CES-D -0.08 CI.95-0.10/-0.06, BDI -0.19 CI.95-0.32/-0.06, HAM-D -1.13 CI.95-1.47/-0.78, and SDS -0.11 CI.95-0.82/0.60). Yet similar effects were observed with estrogens alone and did not significantly differ from control groups on placebo. In one study, the addition of fluoxetine greatly increased the reduction of depressive symptoms observed with estrogen-progestin HT.
CONCLUSIONS: In summary, in randomized clinical trials using validated questionnaires adjunctive progestin with estrogens did not increase depressive symptoms of postmenopausal women. Overall, depressive symptoms decreased with estrogen-progestin HT but also with estrogen alone. The decrease was not so pronounced to differ from controls on placebo. HT does not hamper the clinical efficacy of fluoxetine. The scarcity of randomized studies makes it difficult to determine the exact effect on depressive symptoms of different types of progestins. Project protocol registered in PROSPERO, registration number CRD42023454099.

BACKGROUND: Increased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells.
METHODS: Various POM derivatives were synthesised and characterised by infrared spectra, powder X-ray diffraction pattern and nuclear magnetic resonance spectroscopy. Estrogen receptor (ER) positive breast cancer cells, and their counterparts, which have developed resistance to the hormone therapy tamoxifen, were treated with POMs and their consequences assessed by gel retardation and chromatin immunoprecipitation to determine SOX2 binding to DNA. Effects on proliferation, migration, invasion and tumorigenicity were monitored and quantified using microscopy, clone formation, transwell, wound healing assays, flow cytometry and in vivo chick chorioallantoic membrane (CAM) models. Generation of lentiviral stable gene silencing and gene knock-out using CRISPR-Cas9 genome editing were applied to validate the inhibitory effects of the selected POM. Cancer stem cell subpopulations were quantified by mammosphere formation assays, ALDEFLUOR activity and CD44/CD24 stainings. Flow cytometry and western blotting were used to measure reactive oxygen species (ROS) and apoptosis.
RESULTS: POMs blocked in vitro binding activity of endogenous SOX2. [P2W18O62]6- (PW) Wells-Dawson-type anion was the most effective at inhibiting proliferation in various cell line models of tamoxifen resistance. 10 µM PW also reduced cancer cell migration and invasion, as well as SNAI2 expression levels. Treatment of tamoxifen-resistant cells with PW impaired tumour formation by reducing CSC content, in a SOX2-dependent manner, which led to stem cell depletion in vivo. Mechanistically, PW induced formation of reactive oxygen species (ROS) and inhibited Bcl-2, leading to the death of tamoxifen-resistant cells. PW-treated tamoxifen-resistant cells showed restored sensitivity to tamoxifen.
CONCLUSIONS: Together, these observations highlight the potential use of PW as a SOX2 inhibitor and the therapeutic relevance of targeting SOX2 to treat tamoxifen-resistant breast cancer.

OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no (\"None\"), 6-months (\"Short\"), or 24-mo (\"Long\") ADT to study efficacy in the long term.
METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.
UNASSIGNED: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.
CONCLUSIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.

Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by the spread of uterine leiomyomas to the lungs, typically observed in premenopausal women with a history of hysterectomy or myomectomy. This report presents a unique case of a postmenopausal woman, aged 65, that emphasizes the clinical, radiological, histologic, and immunohistochemical aspects of the disease. On presentation, the patient suffered from severe pain. On imaging, a sizable lung tumor was found. Histopathological examination and immunoprofiling confirmed PBML. The patient underwent various treatments, including surgery, radiation therapy, and hormonal therapy, illustrating the challenges in managing PBML. A literature review underscores the rarity of PBML and its diverse clinical manifestations. This study provides valuable insights into the complexities of PBML.

BACKGROUND: The risk of venous thromboembolism (VTE) with gender-affirming hormone therapy (GAHT) in transgender and gender non-binary (TNB) youth is unclear.
OBJECTIVE: To identify the rate of VTE in a cohort of TNB youth followed in the transgender health clinic at Boston Children\'s Hospital, and to investigate the impact of congenital thrombophilia diagnosis on the use of GAHT.
METHODS: ICD-9 and ICD-10 codes were used to identify eligible individuals, defined as (i) having a diagnosis of gender dysphoria and (ii) venous thromboembolism (VTE). Data were abstracted from a review of medical records. A second data query assessed TNB individuals who had an associated thrombophilia diagnosis.
RESULTS: The primary analysis included 1860 individuals. Total 942 individuals (50.6%) had started GAHT at the time of data analysis. Mean age (±SD) at GAHT initiation was 16.8 (±1.9) years. Five thrombotic events were identified in three (0.13%) individuals, all in the setting of additional VTE risk factors. Only two of five thrombotic events occurred while receiving GAHT. The rate of VTE in the GAHT cohort did not statistically differ from the rate of VTE in the non-GAHT cohort (0.1% vs. 0.2%, p = .62). Of the 10 individuals diagnosed with a congenital thrombophilia, two transmasculine individuals received prophylactic anticoagulation prior to GAHT. No VTE has been reported to date in this cohort.
CONCLUSIONS: In our cohort, VTE was rare in the TNB youth and was not associated with GAHT use. TNB youth with congenital thrombophilia have not developed VTE in the setting of GAHT use to date.

UNASSIGNED: The incidence of prostate cancer is increasing worldwide. A significant proportion of patients develop metastatic disease and are initially prescribed androgen deprivation therapy (ADT). However, subsequent sequences of treatments in real-world settings that may improve overall survival remain an area of active investigation.
UNASSIGNED: Data were collected from 384 patients presenting with de novo metastatic prostate cancer from 2011 to 2015 at a tertiary cancer center. Patients were categorized into surviving (n = 232) and deceased (n = 152) groups at the end of 3 years. Modified sequence pattern mining techniques (Generalized Sequential Pattern Mining and Sequential Pattern Discovery using Equivalence Classes) were applied to determine the exact order of the most frequent sets of treatments in each group.
UNASSIGNED: Degarelix, as the initial form of ADT, was uniquely in the surviving group. The sequence of ADT followed by abiraterone and docetaxel was uniquely associated with a higher 3-year overall survival. Orchiectomy followed by fosfestrol was found to have a unique niche among surviving patients with a long duration of response to the initial ADT. Patients who received chemotherapy followed by radiotherapy and those who received radiotherapy followed by chemotherapy were found more frequently in the deceased group.
UNASSIGNED: We identified unique treatment sequences among surviving and deceased patients at the end of 3 years. Degarelix should be the preferred form of ADT. Patients who received ADT followed by abiraterone and chemotherapy showed better results. Patients requiring palliative radiation and chemotherapy in any sequence were significantly more frequent in the deceased group, identifying the need to offer such patients the most efficacious agents and to target them in clinical trial design.

BACKGROUND: Although several studies report on the suppressing effects of estrogen therapy on facial and body hair in transgender and nonbinary (TGNB) individuals, few studies have elucidated its effects on hairline stability on the scalp. In this study, we assessed the influence of estrogen therapy on forehead length.
METHODS: All TGNB patients, aged 30 years or older, assigned male at birth (AMAB) seeking facial feminization surgery were included in the study. Central and forehead lengths were collected at the initial consultation visits. Variables, including age, duration of hormone replacement therapy (HRT), presence of spironolactone, and presence of other hair treatments, such as finasteride, dutasteride, or minoxidil, that potentially influence hair growth were collected by chart review. Multivariable linear regressions were constructed with relevant predictor variables while also incorporating global health scores as a proxy for psychological effects on hair loss.
RESULTS: Overall, 171 patients were included in this study, with a median age of 36.0 (interquartile range (IQR) 32.0-46.0) years and median HRT duration of 2.0 (IQR 1.0-6.0) years. Multivariable linear regressions revealed no significant predictors for central forehead length. However, lateral forehead length was positively predicted by age (B=0.06, 95% confidence interval (CI) [0.03-0.08], p < 0.001) and hair treatment (B=0.66, 95% CI [0.14-1.18], p = 0.01), but negatively predicted by HRT duration (B=-0.07, 95% CI [-0.10 to -0.04], p < 0.001).
CONCLUSIONS: Although older age is a predictor of lateral hairline recession in TGNB AMAB individuals, lateral forehead length was also predicted to decrease by 0.07 cm with each year of feminizing hormone therapy in patients over 30 years of age.