Original research publications

Although cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are already approved for advanced hormone receptor-positive, HER2-negative breast cancer (HR+/HER2- BC), their efficacy and safety in elderly patients remain incompletely defined. We therefore sought to synthesize the evidence on the efficacy and safety of palbociclib (a CDK4/6i) in elderly HR+/HER2- BC patients. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for studies reporting OS, PFS, and AEs in elderly patients (≥65 years) with HR+/HER2- advanced breast cancer treated with palbociclib. Eligibility criteria included randomized and observational studies with age-specific data. Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. No funding was received. Registration: PROSPERO (CRD42025648485). A p-value of <0.05 denoted statistical significance. We included 3,954 elderly patients treated with palbociclib, of whom 929 (43.2%) had visceral metastases. Palbociclib therapy conferred a significant OS benefit (HR 0.7727; 95% CI 0.6104-0.9780; p = 0.032 and a prolonged PFS (HR 0.6802; 95% CI 0.5452-0.8486; p < 0.001). The most frequent adverse events were neutropenia (RR 5.18; 95% CI 2.65-10.11), decreased white blood cell count (RR 4.80; 95% CI 2.38-9.70), thrombocytopenia (RR 2.57; 95% CI 1.30-5.07), anemia (RR 1.71; 95% CI 1.13-2.58), fatigue (RR 1.06; 95% CI 0.83-1.35), and diarrhea (RR 0.71; 95% CI 0.41-1.24). Palbociclib is associated with significant improvements in both OS and PFS in elderly patients with advanced HR+/HER2- BC. www.crd.york.ac.uk/prospero identifier is CRD42025648485.

Adenomyosis remains challenging to diagnose due to its unclear pathogenesis and clinical overlap with conditions such as endometriosis and uterine fibroids. While non-invasive imaging techniques like transvaginal ultrasound and magnetic resonance imaging have improved adenomyosis detection, histopathological examination remains the gold standard. As this typically requires hysterectomy, it limits fertility-preserving diagnostic options. Therefore, the search for potential biomarkers is essential to improve the diagnosis of adenomyosis. This review summarises current evidence on genomic, transcriptomic, proteomic, metabolomic and microbiome biomarkers identified using conventional molecular techniques and high-throughput multi-omics approaches in eutopic endometrium, blood, urine, faeces, cervicovaginal lavage and vaginal swab samples with potential clinical applicability, enhancing diagnostic accuracy, and enabling early detection and monitoring. In addition, describing adenomyosis biomarkers may enhance the understanding of adenomyosis pathogenesis and help identify new therapeutic approaches. Although numerous candidate biomarkers have shown promising results (e.g. STEAP1, TOMM20, GLT8D2, and NME5, hsa_circ_008959/hsa-miR-124-3p/SLC15A4 + VAS score, miR-92a-3p or Weissella confusa, and Lactobacillus zeae), the current evidence remains insufficient for their implementation in routine clinical practice owing to the lack of external validation, standardised methodologies, and large multicentre studies.

Adenomyosis is an oestrogen-driven, inflammatory uterine disorder characterised by endometrial glands and stroma in the myometrium resulting in abnormal bleeding, pain, and poor reproductive outcomes. Multiple contributors to its pathogenesis and pathophysiology have been identified over the years using a variety of experimental approaches and technologies, with gaps in integrating these approaches into a comprehensive paradigm of adenomyosis pathobiology. This review provides integrative insights from recent studies focused on genetics, multiomics, and advanced computational approaches. These demonstrate that select genes are causally linked to adenomyosis and that genomic and epigenetic mechanisms promote the enhanced oestrogen and diminished progesterone signalling and associated inflammation that are pathognomonic of the disorder, supported by orthogonal validation including novel 3D in vitro cell models. In addition, advanced computational tools, including AI-driven platforms that integrate multiomics data, reveal promising therapeutic candidates for mitigating disease progression and symptoms and improving fertility and pregnancy success.

Vertical transmission of HIV remains a significant challenge to maternal and child health in high burden settings. Early identification of maternal HIV status enables timely antiretroviral therapy initiation and helps prevent transmission during pregnancy, childbirth, and breastfeeding. This study explored barriers to HIV testing uptake among pregnant and postpartum women attending antenatal care (ANC) services in Soweto, Johannesburg. A qualitative research design was employed, involving in-depth interviews with ten adult women who accessed ANC services. Data were analysed thematically using Atlas.ti 23 software. Findings revealed multilevel barriers across the socio-ecological spectrum. At the individual level, fear of HIV testing and its potential outcomes discouraged uptake. Interpersonal factors, particularly partner and family influences, shaped women's testing decisions. Institutional barriers included negative healthcare providers attitudes, inadequate privacy, and insufficient counselling. At the community level, stigma amd discrimination discouraged HIV testing, while systematic barriers included gaps in implementing and enforcing HIV testing policies. These findings highlight the need for intergrated interventions addressing individual, interpersonal, community, institutional and systemic barriers. Strengthening confidentiality, improving healthcare provider communications, reducing stigma and enhancing policy implementation may improve HIV testing uptake among pregnant and postpartum women and streghthen maternal HIV prevention services.

The use of plant, algal, microbial or biomolecule based reducing and capping agents to synthesize gold nanoparticles (AuNPs) has paved the way for the use of these materials as versatile candidates for breast-cancer nanomedicine. In addition to being a more sustainable synthetic pathway, the biological elements attached to the surface of AuNP can have an impact on the formation process, the stability of AuNP in solution, the interaction with cells and the therapeutic activity of the particles. This review critically assesses the recent advances of biogenic AuNPs for application in breast cancer, ranging from direct phytogenic anticancer formulations, engineered drug delivery system, HER2 associated biosensing platform, photoresponsive therapies, and multimodal theranostic constructs. Preclinical reported mechanisms are increased cellular uptake, increased oxidative stress, mitochondrial dysfunction, increased DNA damage, cell-cycle arrest, and apoptosis. Additionally, Biogenic AuNPs offer flexible surfaces for the conjugation of chemotherapeutics, phytochemicals, nucleic acids, antibodies, photosensitizers and tumour-targeting ligands, thus providing opportunities for subtype-specific strategies for HER2-positive disease and triple-negative breast cancer. Currently however, in vitro studies dominate the evidence base, and many of these studies make use of limited models of cell lines. Although the bioinorganic nature of Biogenic AuNPs is scientifically interesting, their clinical applicability will rely on the development of reproducible synthesis procedures, characterization in biological environments, validation for the respective sub-type, quantitative biodistribution and clinically representative preclinical models.

Vaginal microenvironment disorder is related to cervical lesion development, and neutrophil extracellular traps (NETs) participate in tumour progression. Whether vaginal microecology indicators are associated with NET markers in vaginal secretions has not been examined. To quantify the association between vaginal microecology indicators and vaginal secretion NET marker levels across cervical lesion grades. Two hundred women formed control, cervicitis, low-grade and high-grade squamous intraepithelial lesion groups (n = 50, 50, 51, 49). Thirteen vaginal microecology indicators and HPV genotype were recorded. In 35 stratified vaginal secretion supernatants, myeloperoxidase-DNA (MPO-DNA), citrullinated histone H3 (CitH3) and cell-free DNA (cfDNA) were measured. Spearman correlation and linear regression were applied. NET scores in GSE63514 and GSE7803 were derived by ssGSEA. Individual microecology indicators did not differ across groups after false discovery rate (FDR) correction. MPO-DNA and Cit-H3 were elevated in HPV-positive groups versus controls (P ≤ 0.003) without differing among lesion groups. Leukocyte esterase correlated with MPO-DNA (rho = 0.528, FDR = 0.037) and Cit-H3 (rho = 0.455, FDR = 0.049), and remained associated with MPO-DNA after adjustment for leukocyte grade (partial rho = 0.441, P = 0.009). In GSE63514, NET score increased with lesion grade (P = 0.003) and correlated with neutrophil infiltration (rho = 0.547, P < 0.001), which was not replicated in GSE7803 (trend P = 0.623). Vaginal inflammatory indicators, particularly leukocyte esterase, are positively associated with vaginal secretion MPO-DNA levels, reflecting local neutrophil-related inflammation rather than a mediating link in cervical lesion progression.

Cellular and gene-based therapies are being investigated as potential strategies to address current treatment limitations in breast cancer. Adoptive cell therapies, such as CAR-T, TCR-T, TILs and NK cell-based therapies, are currently under investigation for their ability to selectively target tumor-associated antigens. Also, CRISPR/Cas9-mediated genome editing is being investigated as a strategy to enhance T cell persistence, improve tumor infiltration, and increase resistance to immunosuppressive signaling. Although cellular and gene-based therapies have transformed the treatment of hematologic malignancies, their application in breast cancer remains limited by antigen heterogeneity, immune exclusion, and the immunosuppressive tumor microenvironment. Among current approaches, TIL-based therapies have provided some of the clearest evidence of clinical activity selected patients, whereas the clinical efficacy of CAR-T and gene-editing strategies as standalone interventions remains uncertain. Future progress may depend on biomarker-guided, combinatorial approaches rather than single-modality therapies. This review examines the current applications, clinical evidence, and limitations of these approaches in breast cancer.

Obesity is a well-established risk factor for increased incidence and mortality in multiple cancers, including breast cancer. However, the key molecular mechanisms linking obesity to breast cancer progression remain incompletely understood. In this study, using several high-fat diet-induced obesity models, we demonstrate that obesity promotes breast cancer lung metastasis through elevated levels of adipocyte-derived circulating FABP4. Mechanistically, circulating FABP4 directly binds to a subset of breast cancer cells via the membrane lipid PIP2. This FABP4/PIP2 interaction activates PKC signaling and enhances mitochondrial ROS production, driving cancer cell migration. Genetic deletion of FABP4, either globally or specifically in adipocytes, markedly reduces obesity-associated metastasis. Moreover, therapeutic targeting of circulating FABP4 using a distinctive neutralizing monoclonal antibody significantly suppresses breast cancer metastasis in multiple preclinical models. Together, these findings identify the FABP4/PIP2 axis as a key mechanism underlying obesity-driven breast cancer and highlight it as a promising therapeutic target for treating metastatic breast cancer.

Globally, polycystic ovary metabolic syndrome (PMOS) affects 5% to 20% of women of childbearing age. Despite the high burden of ambient air pollution in the Middle East, epidemiological evidence linking long-term exposure to PMOS remains limited. This cross-sectional study examined associations between long-term residential exposure to criteria air pollutants and PMOS prevalence in Arak, Iran. We enrolled 301 women (153 PMOS cases, 148 non-PMOS controls) from gynecology clinics (April 2024-March 2025). Long-term (365-day) residential exposures were estimated using inverse distance weighting (IDW) interpolation from three fixed monitoring stations. Modified Poisson regression was prioritized to estimate prevalence ratios (PRs), given the high prevalence of the outcome. Robustness was assessed via alternative exposure windows (90-day, 30-day), extreme value exclusion, and propensity score matching. Women with PMOS had significantly higher exposures to PM 2 . 5 (mean difference: 3.00 μg/m 3 ), PM 10 (7.50 μg/m 3 ), NO 2 (2.96 ppb), and SO 2 (11.35 ppb) (all p ≤ 0.025). Per 1-SD increase, adjusted PRs were: PM 2 . 5 = 1.22 (95% CI: 1.09-1.35; p = 0.001); PM 10 = 1.23 (95% CI: 1.09-1.36; p = 0.001); NO 2 = 1.21 (95% CI: 1.07-1.33; p = 0.003); and SO 2 = 1.15 (95% CI: 1.01-1.28; p = 0.032). All sensitivity analyses supported the robustness of these associations. Exploratory analyses suggested specificity to menstrual/ovulatory dysfunction. This first Middle Eastern study reports statistical associations between long-term PM 2 . 5 , PM 10 , NO 2 , and SO 2 exposure and PMOS prevalence in a high-pollution industrial setting. Because of the cross-sectional design, these findings cannot establish causality and are strictly hypothesis-generating, highlighting the urgent need for prospective cohort studies.

Follow-up care after a positive human papillomavirus (HPV) screening result is essential for cervical cancer prevention, yet many individuals do not complete diagnostic evaluation or treatment. We conducted a systematic review to synthesize barriers to follow-up care after a positive HPV screening result across diverse international settings. The protocol was registered in PROSPERO (CRD420251062691). We searched MEDLINE, Embase, Scopus, and Web of Science for English language studies published from 2015 to 2025. Two reviewers independently screened studies, and findings were narratively synthesized. Fifteen studies met inclusion criteria, and were conducted across 12 locations in Africa, Europe, North America, and South America. Five barrier groups emerged: health system barriers (lack of local treatment, long wait times, limited follow-up capacity), knowledge and communication barriers (confusion about HPV results and next steps), psychological and emotional barriers (fear of treatment, stigma surrounding HPV, distrust in medical systems), social and relational barriers (partner influence, gender roles, lack of peer support), and structural and logistical barriers (transportation, costs, work conflicts). Across settings, missed follow-up after positive HPV screening appeared more strongly linked to health-system and structural barriers than lack of motivation. Strengthening referral pathways, patient tracking systems, communication of results, navigation support, and timely treatment access may improve follow-up completion and enhance the effectiveness of HPV-based screening programs.

Magrolimab blocks CD47, a molecule that mediates cancer immune evasion from phagocytes. The ELEVATE TNBC study evaluated magrolimab plus standard-of-care therapies in advanced/metastatic triple-negative breast cancer (mTNBC). Two cohorts were enrolled in the safety run-in (SRI) and phase II portions. Phase II cohort 1 randomly assigned 28 patients with untreated, programmed death-ligand 1-negative mTNBC to receive nab-paclitaxel or paclitaxel with/without magrolimab. Phase II cohort 2 enrolled 43 patients with mTNBC (one to two prior lines of treatment in the metastatic setting) to receive magrolimab with sacituzumab govitecan. Primary endpoints were adverse event (AE) incidence (SRIs), investigator-assessed progression-free survival (PFS; phase II cohort 1), and objective response rate (ORR; phase II cohort 2). No dose-limiting toxicities occurred. In phase II cohort 1, median PFS was 13.9 and 10.0 months (hazard ratio 0.456, 95% confidence interval 0.147-1.409) and ORRs were 35.7% and 21.4% for magrolimab-taxane and taxane therapy, respectively. In phase II cohort 2, ORR was 38.1%, and median PFS was 5.5 months. Early study closure limited interpretation of efficacy; PFS/ORR values should be considered descriptive. AE rates were consistent with known profiles for each agent, with no new safety signals or fatal AEs. Magrolimab plus standard of care was manageable. Further studies are needed to determine the role of anti-CD47 therapies in mTNBC.

Many young women treated for gynecological cancer are assumed to experience long-term concerns about fertility and pregnancy, and psychological distress. However, evidence on patients' post-treatment reproductive concerns, decisions to pursue pregnancy, and oncofertility needs is limited. This study aims to provide insight into the perspectives of women treated with fertility-sparing surgery (FSS) for gynecological cancer and their partners. Women and their partners were selected for semi-structured interviews from our previously performed questionnaire study through purposive sampling based on self-reported reproductive concerns and pregnancy attempts. Interviews were coded and analyzed using a framework approach until data saturation was reached. Data saturation was achieved after 32 interviews with 24 participants and eight partners. Three participants did not pursue pregnancy and decided not to in the future. Participants expressed reproductive concerns and encounter post-treatment challenges, including a sense of time pressure, fear of cancer recurrence, and a common need for assisted reproductive techniques. Nearly all participants expressed their need for post-operative fertility counseling, although the preferred timing for this support varied. Partners considered their primary role as providing support throughout the treatment (decision) process, deciding to conceive and pursuing pregnancy. Some partners emphasized the importance, but lack of partner support. Women treated with FSS for gynecological cancer and their partners face persistent uncertainty regarding fertility and pregnancy, yet most women remain motivated to pursue pregnancy. Partners play a supportive role, but also have unmet needs. These findings highlight that reproductive issues should be systematically incorporated into routine clinical care pathways.

Neonatal opioid withdrawal syndrome (NOWS) severity is influenced by several clinical factors; however, the association with infant sex is poorly understood. We examined the association between infant sex and NOWS severity in a cohort of buprenorphine-exposed infants. This was a secondary analysis of the MOMS clinical trial (NCT03918850). Regression models evaluated the association between infant sex and NOWS severity measures, including (1) receipt of any pharmacologic treatment, (2) opioid treatment days, (3) adjunctive medication treatment, (4) length of hospital stay (LOS), and (5) LOS related to NOWS. There were 135 infants (67 male, 68 female). There were no significant differences in demographics or medical comorbidities by infant sex. Methamphetamine and phencyclidine exposures were positively associated with receipt of any pharmacologic treatment, and phencyclidine with longer LOS. Breastfeeding was associated with decreased receipt of any pharmacologic treatment and shorter total LOS, and preterm delivery and NICU admission with longer total LOS. In final regression models, NOWS severity did not differ by infant sex. Infant sex was not statistically associated with NOWS severity measures within this buprenorphine-exposed cohort. Meta-analyses are needed to better understand the relationship between infant sex and NOWS.

Germline data from African populations remain sparse, limiting characterization of population-specific BRCA1/2 pathogenic variants (PV). In a study of 175 Rwandan women with breast cancer, 7 unrelated carriers (4% of cases; 22% of PV carriers) harbored the same BRCA1 frameshift PVs, c.4065_4068del (p.Asn1355Lysfs*10), which is extremely rare in gnomAD yet recurrent in European, Asian, and Middle Eastern cohorts. Whole-exome sequencing and haplotype analysis of all 7 carriers revealed a shared ancestral block of approximately 581 kb surrounding the variant, and extended haplotype homozygosity and network analyses confirmed a common founder origin. Coalescent-based age estimation placed the founder event approximately 4,000--10,000 years ago. Comparison with 1000 Genomes Project data showed the founder haplotype is absent or exceedingly rare outside African and South Asian populations. These findings strongly suggest the c.4065_4068del variant as a pre-historical BRCA1 founder variant in Rwanda, with implications for targeted genetic testing, cascade screening, and cancer prevention in the region.

Radiotherapy is the mainstay for locally advanced cervical cancer, but its efficacy is compromised by radioresistance. Dysregulated lipid metabolism contributes to therapeutic resistance, offering a promising strategy to improve radiosensitivity. This study aimed to explore the effect and mechanism of baicalein in enhancing radiosensitivity of cervical cancer cells. In vitro experiments were performed to assess the radiosensitizing effect of baicalein, while potential targets were identified through bioinformatics and network pharmacology. The key target was further validated by gene knockdown, and in vivo experiments were conducted to confirm the effects of baicalein combined with radiotherapy. ALOX15 was identified as a key target of baicalein, and high ALOX15 expression was associated with poor prognosis in cervical cancer. Both baicalein treatment and ALOX15 suppression enhanced radiosensitivity, reduced lipid droplet accumulation, and downregulated the SREBP1/FASN/ACC protein expression. In vivo , baicalein combined with radiotherapy reduced lipid accumulation and serum lipid levels, with effects comparable to those of the ALOX15 inhibitor AA861. Collectively, these findings suggest that baicalein enhances radiosensitivity in cervical cancer by targeting ALOX15 and modulating lipid metabolism via the SREBP1/FASN/ACC pathway. ALOX15 may be a potential regulator of radioresistance, and baicalein warrants further investigation as a potential radiosensitizer.

Parenthood and pregnancy are important life goals for many individuals, including those with CKD. However, fertility concerns and their impact on quality of life (QoL) are often overlooked in people with complex medical needs. The Fertility QoL (FertiQoL) questionnaire is a validated tool that assesses fertility-related QoL across six domains. This study aimed to assess FertiQoL in women with CKD compared to healthy control women of reproductive age. We conducted a case-control study including 102 women with CKD and 84 healthy controls. Participants completed the FertiQoL survey during a study visit. Domain and total scores were compared between groups, with subgroup analyses among women with prior fertility treatment, those actively trying to conceive, and nulliparous women. Findings were reviewed with an independent expert patient group of women with CKD to evaluate result interpretation and co-develop recommendations. Women with CKD and controls were similar in age, BMI, parity and history of conception attempts. Median total scaled FertiQoL score was significantly higher in women with CKD than healthy controls (66.2 [IQR 54.8-77.8] vs. 56.6 [IQR 50.5-64.1]; p < 0.001). Women with CKD also had significantly higher scores in emotional, mind-body and social domains. However, among women with prior fertility treatment or those actively trying to conceive, fertility-related QOL did not differ significantly by CKD status. The expert patient group suggested these findings were an adaptation to the demands of long-term ill health rather than any underlying differences in reproductive aspirations. This is the first study to assess fertility-related QoL in CKD. Women with CKD reported comparable or better fertility-related quality of life than controls, likely reflecting adaptation to chronic illness. Fertility remains a key priority for women with CKD, highlighting the need for proactive, multidisciplinary fertility counselling and access to reproductive care.

Adjuvant endocrine therapy (AET) reduces recurrence and mortality for women with early-stage hormone receptor-positive breast cancer, yet long-term adherence is suboptimal, largely due to treatment-related symptoms. Remote patient monitoring (RPM) is a potential strategy to improve symptom management, but evidence of its cost-effectiveness is limited. To evaluate the cost-effectiveness of RPM for women prescribed AET for early-stage breast cancer. This economic evaluation used data from the THRIVE trial, which randomized adult women initiating AET to an application (app), the app with tailored feedback, or enhanced usual care (EUC) at a large cancer center with 14 clinics from November 15, 2018, to June 11, 2021. The intervention lasted 6 months, and participants were followed up for 12 months (completed September 19, 2022). Each of the 2 interventions was compared with EUC, with uncertainty assessed using probabilistic sensitivity analyses. Data analyses were performed from February 1, 2025, to September 2, 2026. Primary outcomes included costs, which were captured during the 12-month study period from a societal perspective, including medical costs, patient time and travel costs, clinician time costs responding to alerts, and app costs; quality-adjusted life years (QALYs), derived from patient-reported 12-item Short Form Health Survey scores; incremental cost-effectiveness ratios; and incremental net monetary benefit. Of 304 participants randomized, 214 had complete data. The mean (SD) age was 58.9 (10.8) years. Mean (SD) total costs were highest for the EUC arm ($11 596.10 [$30 231.95]) compared with the app arm ($6682.15 [$12 963.34]; difference, -$4913.95 [95% CI, -$12 864.27 to $3036.37]) and app plus feedback arm ($11 407.85 [$47 068.42]; difference, -$188.25 [95% CI, -$12 830.16 to $12 453.66]). The mean (SD) estimated QALYs were similar across arms (app, 0.79 [012]; app plus feedback, 0.78 [0.13]; EUC, 0.78 [0.12]). This results in an incremental net monetary benefit of $5813.95 (95% uncertainty interval [UI], -$1860.00 to $16 492.58) for app group and $88.25 (95% UI, -$14 781.73 to $13 849.34) for the app plus feedback group at $100 000 per QALY. Probabilistic sensitivity analyses suggest that the app intervention had a 68.2% to 78.1% probability of being cost-effective compared with EUC across a willingness-to-pay threshold of $0 to $200 000 per QALY, while the app plus feedback intervention had a 53.6% to 70.8% probability of being cost-effective. In this economic evaluation of RPM for women receiving AET, app-only RPM showed lower costs with similar QALY compared with EUC. Its simpler design may also be more readily scalable than the app plus feedback intervention, supporting its potential as a pragmatic, value-based supportive care strategy in oncology.

Although surveillance mammography is commonly performed among older women, whether this practice improves clinical outcomes in this population is uncertain. To evaluate the association between surveillance mammography and second primary breast cancer stage at diagnosis among older women with a history of breast cancer. This retrospective longitudinal cohort study used Surveillance, Epidemiology, and End Results Program-Medicare data. Women with nonmetastatic breast cancer that was diagnosed from 2004 to 2008 at 67 years or older who had a surveillance mammogram at approximately 5 years after diagnosis were included. Analyses used cause-specific hazard models with inverse probability of treatment weighting to estimate the risk of stage-specific second primary breast cancer among women who continued surveillance mammography and those who did not. Analyses were stratified by hormone receptor (HR) status of the initial breast cancer. Follow-up continued until second breast cancer diagnosis, death, or end of the study (December 2021). Analyses were performed between November 2025 and August 2026. Continued surveillance mammography more than 5 years after initial diagnosis. Stage-specific cumulative incidence of a second primary breast cancer, categorized as in situ, localized, or advanced (regional or distant). Among 9888 women (mean [SD] age, 81.1 [5.5] years; 387 Hispanic [3.9%], 514 non-Hispanic Black [5.1%], and 8514 White individuals [86.1%]), 8055 (81.4%) had in situ or localized disease and 7621 (76.9%) had HR-positive tumors at initial diagnosis. Overall, 7940 women (80.3%) continued surveillance at cohort entry. Advanced second primary breast cancer was rare, and incidence did not differ among those who continued surveillance and those who did not (cumulative incidence, 1.65% vs 2.15%; hazard ratio, 0.76; 95% CI, 0.46-1.26). Results were similar in subgroups of women with initial HR-positive and HR-negative breast cancer. The results of this cohort study suggest that among older survivors of breast cancer, continued surveillance mammography was not associated with a reduced risk of advanced second primary breast cancer. The absolute risk of advanced cancer was low, and surveillance decisions should be individualized given the potential burdens of continued surveillance.

Little is known about neurodevelopmental outcomes of children exposed to SARS-CoV-2 messenger RNA (mRNA) vaccine during pregnancy. Evidence on long-term offspring outcomes after in utero exposure to SARS-CoV-2 mRNA vaccination is needed to inform vaccine recommendations in pregnancy. To evaluate whether there is an association between SARS-CoV-2 vaccination during or shortly before pregnancy and offspring neurodevelopmental measures. This multicenter, prospective, cohort study of 18- to 30-month-old children was conducted at 14 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 2024 through 2025. Women who received a SARS-CoV-2 mRNA vaccine during or within 30 days prior to pregnancy (exposed) were matched with women who did not (unexposed) by delivery site, delivery date, insurance status, and race and ethnicity. These data were analyzed from June 2025 to May 2026. Maternal receipt of at least 1 dose of an mRNA SARS-CoV-2 vaccine during, or within 30 days prior to, the index pregnancy vs no SARS-CoV-2 vaccination during pregnancy or within 30 days prior. The primary outcome was Ages and Stages Questionnaire version 3 (ASQ-3) total score, which was deemed to be equivalent between the exposed and unexposed groups if the 90% CI of the median difference was between -10 and 10. Secondary outcomes included domain-specific ASQ-3 scores, the Child Behavior Checklist, Modified Checklist for Autism in Toddlers, and Early Childhood Behavior Questionnaire scores. Of 3956 screened, 271 exposed and 240 unexposed children were enrolled. Matching on all characteristics was possible in 217 pairs. Of the 434 children enrolled, 258 (59.4%) were Non-Hispanic White, 96 (22.1%) Non-Hispanic Black, 52 (12.0%) Hispanic, and 28 (6.5%) were not represented by any of the above racial or ethnic groups. Median age at assessment was 25.8 [24.6 to 28.3] months, 221 were female (50.9%), and 213 were male (49.1%). Exposed mothers were more likely to be nulliparous; their children were slightly younger at assessment and more likely to have been vaccinated against SARS-CoV-2. The primary outcome of ASQ-3 score was equivalent between the exposed and unexposed groups (255 vs 260, adjusted median difference, -3.4; 90% CI, -9.8 to 3.0). There were no significant differences in secondary outcomes. In this multicenter cohort study, ASQ-3 scores were equivalent between 18- to 30-month-old children whose mothers did or did not receive mRNA SARS-CoV-2 vaccination during or immediately prior to pregnancy. These findings support continued recommendations for SARS-CoV-2 mRNA vaccination during pregnancy.

Accurate breast cancer molecular subtype classification is important for treatment planning, but immunohistochemical assessment may be affected by intratumoral heterogeneity and requires invasive tissue sampling. We hypothesize that segmentation-guided learning of tumor-core and peritumoral microenvironment (PTM) MRI features would improve molecular subtype discrimination over tumor-core-only analysis. A transformer-based segmentation network integrates cross-modal and multi-scale features to delineate tumors, after which the predicted masks are used to construct tumor-core and peritumoral inputs for an energy-regularized classification network. On the test cohort, the retrospective single-center study includes 381 patients with histopathologically confirmed breast cancer and corresponding DCE, DWI, T1WI, and T2WI images. The proposed method achieves a Dice coefficient of 88.29%, a Jaccard index of 79.80%, a precision of 91.98%, and a 95HD of 4.03 pixels for tumor segmentation. For molecular subtype classification, it achieves an accuracy of 84.0%, a macro-averaged sensitivity of 85.7%, a macro-averaged specificity of 94.8%, and a macro-averaged F1 score of 83.9%, providing the best overall performance among the evaluated methods. These findings support further evaluation of segmentation-guided multimodal MRI analysis for preoperative molecular subtype assessment.

Postoperative recurrence remains a major cause of treatment failure in breast cancer, largely because microscopic residual disease persists within a biologically active surgical niche characterized by inflammation, immune suppression, and spatially irregular tumor beds. In this review, we critically evaluate whether combining a precisely defined platelet-derived module, an injectable hydrogel, and CAR-T cells can provide nonredundant advantages over standard treatment and simpler local or pairwise alternatives in postoperative breast cancer. Platelet-inspired delivery systems exploit endogenous injury-homing and adhesion biology to improve localization to damaged vasculature and disease-relevant tissue, while hydrogels provide cavity-conformal retention, prolonged local release, and spatial control of therapeutic exposure within irregular surgical beds. CAR-T cells confer antigen-directed cytotoxicity to eliminate residual malignant cells that survive surgery and conventional adjuvant treatment. Importantly, the supporting evidence is tiered rather than uniform. Most studies have evaluated individual modules or selected pairwise combinations that directly support functions such as injury-associated localization, local retention, or antigen-directed cytotoxicity. Direct evidence of postoperative breast cancer is currently limited to intact platelet-B7-H3 CAR-T conjugates, a pairwise product that contains neither an injectable hydrogel nor a platelet-membrane-coated nanocarrier. The closest three-component precedent used a hyaluronic acid hydrogel to co-deliver CSPG4-directed CAR-T cells, IL-15-loaded polymer nanoparticles, and intact anti-PD-L1-conjugated platelets after resection of subcutaneous human melanoma in NSG mice. No published study has directly tested this defined platelet-membrane-coated nanocarrier-hydrogel-CAR-T product in postoperative breast cancer; therefore, interpret the construct discussed here as a hypothesis-driven, critical design perspective rather than a validated, disease-specific platform. We further discuss the potential of this integrated approach to improve control of microscopic disease within or immediately adjacent to the surgical bed and to remodel the local postoperative immune microenvironment. However, effects on regional nodal or distant relapse remain unproven and would require integration with regional radiotherapy and subtype-directed systemic therapy. Finally, we highlight the major barriers that must be resolved before clinical translation, including platelet-associated thrombogenicity, off-target biodistribution, CAR-T trafficking and persistence, antigen heterogeneity, manufacturability, and the need for predictive biomarker-guided patient selection. Collectively, this review reframes the postoperative breast cancer bed as a programmable therapeutic microenvironment and outlines a rational roadmap for next-generation adjuvant immunoengineering.

To evaluate the clinical phenotype and interpretability of TEX15 gene variants in a real-world cohort of patients with primary testicular disease. We conducted a retrospective single-center study including patients with primary testicular dysfunction. Patients carrying isolated TEX15 gene variants (n = 7) were compared with a pathological control group (n = 145) from a cohort of infertile patients with primary testicular failure without identifiable genetic alterations. Clinical, hormonal, and seminal parameters were analyzed using non-parametric tests. Effect size was estimated using Cliff's delta. TEX15 gene variants were identified in 0.9% of the cohort. No pathogenic biallelic variants were identified. Compared to pathological controls, TEX15-positive patients showed lower FSH concentrations (p = 0.031), higher sperm concentration (p = 0.002), and higher total sperm count (p = 0.002). Azoospermia was absent among TEX15 cases but present in 62.1% of controls (p = 0.002). No significant differences were observed in LH, testosterone levels, estradiol concentrations, or testicular volume. Sensitivity analyses excluding biologically atypical subjects attenuated most observed differences. Overall, TEX15-positive patients showed heterogeneous clinical presentations with limited phenotypic specificity compared to other forms of primary testicular dysfunction. Our findings indicate that TEX15 gene variants, particularly in heterozygous state, have limited clinical interpretability and do not define a clearly distinguishable clinical phenotype. These findings suggest that isolated TEX15 variants, particularly in heterozygous state, should be interpreted cautiously in routine male infertility diagnostics pending further functional validation.

Breast cancer surgery is generally considered to be low risk for venous thromboembolism (VTE). However, when VTE occurs, it may lead to severe complications and increased mortality. This study aimed to determine the incidence, predictors, and clinical impact of postoperative VTE following breast cancer surgery using a large, multicenter surgical database. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2023) was queried to identify female patients undergoing surgery for breast cancer without concurrent reconstruction. Patients were stratified according to postoperative VTE occurrence. Demographics, comorbidities, laboratory values, operative characteristics, and 30-day outcomes were compared. Multivariable logistic regression was used to identify independent predictors of VTE and to construct a predictive model, which was internally validated using bootstrap resampling. Among 270,564 patients included, 465 (0.2%) developed postoperative VTE. Of these, 247 (53.1%) had deep vein thrombosis, 177 (38.1%) pulmonary embolism, and 41 (8.8%) both. Patients who developed VTE were older, had higher body mass index (BMI), greater comorbidity burden, and longer operative times (all p < 0.001). They also demonstrated lower preoperative serum albumin, hematocrit, prothrombin time, and albumin-to-creatinine ratio. VTE was associated with significantly longer hospital stays, increased rates of reoperation and readmission, and a more than 20-fold higher crude 30-day mortality (1.9% vs. 0.1%) (all p < 0.001). In multivariable analysis, increasing age (OR 1.26 per 10 years), BMI (OR 1.17 per 5 kg/m²), congestive heart failure (OR 2.43), metastatic cancer (OR 2.05), lower serum albumin (OR 0.63 per 1 g/dL), and longer operative duration (OR 1.09 per 30 min) were independently associated with postoperative VTE. Compared with partial mastectomy, total mastectomy (OR 2.58), modified radical mastectomy (OR 2.22), and radical mastectomy (OR 2.80) were associated with significantly higher odds of postoperative VTE. The predictive model demonstrated acceptable discrimination (AUC 0.717; optimism-corrected 0.700) and good calibration. Age, BMI, congestive heart failure, metastatic cancer, mastectomy and operative time remained associated with VTE in all sensitivity analyses. Postoperative VTE following breast cancer surgery is uncommon but associated with substantial morbidity and mortality. Advanced age, obesity, cardiac comorbidity, metastatic disease, hypoalbuminemia, longer operative duration, and greater surgical extent were independently associated with increased thromboembolic risk. Awareness of these risk factors may support individualized perioperative risk assessment and thromboprophylaxis decisions, as recommended by current consensus guidance, and facilitate earlier recognition of postoperative VTE. Not applicable.

Black women with breast cancer in the US experience worse survival and lower quality of life. Addressing information needs and providing emotional and social support may improve survivorship experiences. This study evaluated feasibility and acceptability of an intervention to support Black breast cancer patients. English-speaking, Black, female breast cancer survivors diagnosed with stage I-III breast cancer within five years were invited to participate in a six-week group intervention (virtual or in-person). The intervention was adapted from the PAVING the Path to Wellness program based on a prior qualitative study. Primary endpoints were feasibility and acceptability. Exploratory endpoints included unmet information needs and well-being. Exit interviews with a subset of participants described experiences with, and benefits from, the intervention. 20 women with a mean age of 59.1 years (SD 8.2) and predominantly diagnosed at stage I (n = 11; 55%) participated. Most participants (n = 15; 88.3%) reported high levels of satisfaction and that the program provided new information relevant to their needs and helped motivate lifestyle changes. Nearly all participants (n = 15; 88.3%) expressed that it is important for other Black breast cancer survivors to receive a similar intervention. This study demonstrates proof of concept and provides insights into participant preferences. Broader-scale testing is needed to assess generalizability. NCT05700396, Registration Date: 2023-01 -17.

Hypertensive disorders of pregnancy are risk factors for later cardiovascular and chronic kidney disease. Early postpartum trajectories of blood pressure and metabolic recovery in this high-risk population are still insufficiently defined. A prospective, single-center, observational cohort study was conducted in the Cardiovascular-Kidney-Metabolic Women's Healthcare Prevention Program (PreCareFem) at the University Hospital St. Pölten, Austria. Participants were enrolled on presentation between 1 June 2023, and 31 March 2025. Cardiovascular and metabolic surrogate parameters, including automated blood pressure measurement, anthropometric evaluation, cardiovascular, kidney and metabolic parameters, lifestyle assessment following the components of the "Life's Essential 8", and urine albumin-creatinine ratio were assessed peripartum and at 3-6 and 12 months postpartum. A total of 91 women with preeclampsia (PE; n = 66) and gestational hypertension (GH; n = 25) were enrolled. At 12 months postpartum, 31% met the diagnostic criteria for arterial hypertension (PE 29%, GH 36%), 18% for prediabetes and 3% for diabetes. More than half (52%) had LDL levels > 100 mg/dL and 32% had low HDL levels. Obesity was diagnosed in 24% of participants, 8% of women were diagnosed with CKD 12 months postpartum. Low-grade albuminuria (uACR 10-30 mg/g) was observed in 21% of women with PE compared to 8% in women with GH. A significant number of women were diagnosed with arterial hypertension, early kidney impairment and/or metabolic abnormalities 1 year following hypertensive disorders of pregnancy. These findings highlight the need for a structured, multidisciplinary postpartum follow-up to address an underutilized opportunity for prevention of cardiovascular and chronic kidney disease.

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative tumors are the most common types of breast cancer. Mutation of ESR1 complicates their therapy. On September 04, 2026, camizestrant (Etcamah ® ) received approval for HR-positive and HER2-negative, locally advanced or metastatic breast cancer after detecting ESR1 mutation during medication with aromatase and CDK4/6 inhibitors. The mutation was identified through circulating tumor deoxyribonucleic acid, thus representing its first interventional use to guide a therapy switch as part of a clinical study. Camizestrant is a selective estrogen receptor degrader (SERD) and complete antagonist of the estrogen receptor. A dose of 75 mg is taken by mouth once daily concomitantly with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. In a drug regimen comprising an aromatase inhibitor along with a CDK4/6 inhibitor, a significant improvement in progression-free survival was achieved when the aromatase inhibitor was exchanged for camizestrant. This makes camizestrant a next-generation oral SERD for treating advanced breast cancer. The image identifies three chemical groups within the camizestrant molecule and associates each with a specific functional role: one group controls the degradation profile, another regulates basicity and lipophilicity, and a third influences solubility and protein binding. Additionally, the image includes a pink ribbon labeled with the breast cancer classifications ESR1, HR-positive, and HER2-negative.

To evaluate the clinical and economic impact of a structured breast cancer early detection initiative incorporating active recall and nurse navigation within a private healthcare cooperative in Brazil's supplemental health sector. A 2-year initiative was implemented across a cooperative serving 140 000 beneficiaries. Active recall and nurse navigation were combined to improve screening adherence. Real-world administrative claims data captured direct medical costs across the continuum of care. A Markov state-transition model compared costs and outcomes between the early detection scenario and a metastatic counterfactual. A complementary cost-only analysis expressed outcomes in monetary terms. Over 2 years, 1999 mammograms increased screening coverage from 52% to 66%, generating appropriate downstream procedures and identifying 2 breast cancer cases. Total expenditures for screening and early-stage treatment reached R$702 485.00. The HER2-positive case identified was estimated to have incurred R$1 653 704.00 in metastatic treatment costs without early detection. Avoided expenditures resulted in net savings of R$951 219.00 and a 135% return on investment. The early detection strategy demonstrated economic dominance, with lower costs and greater expected health benefit. A coordinated model combining active recall and nurse navigation demonstrated feasibility, scalability, and meaningful clinical and economic value in a fragmented care environment. Early detection represents a strategically dominant intervention for improving oncological outcomes and enhancing financial sustainability in Brazil's supplemental health sector and similar hybrid systems.

Growth differentiation factor (GDF)-15 is a stress-responsive cytokine induced by mitochondrial dysfunction and genotoxic stress, mechanisms central to anthracycline cardiotoxicity. Whether early changes in GDF-15 following cancer therapy relate to subsequent cardiac dysfunction is not established. We evaluated the longitudinal trajectory of GDF-15 and its associations with changes in cardiac function and structure following cardiotoxic cancer therapy in women with breast cancer. In 366 women receiving anthracyclines and/or trastuzumab from the Penn Cardiotoxicity of Cancer Therapy prospective cohort study, associations between baseline, early-peak (maximum 0-6-month change), and longitudinal GDF-15 concentrations with quantitative echocardiographic measures of systolic, diastolic, and structural function over 36 months were evaluated using multivariable linear mixed-effects models. GDF-15 rose from a median baseline of 662 to an early-peak of 1,412 pg/mL, with trajectories differing across regimens (P = 0.004). Each doubling of the early-peak-to-baseline GDF-15 ratio was associated with a subsequent 1.5 percentage point decline in left ventricular ejection fraction (β -1.5%; 95% CI: -2.5 to -0.6; P = 0.002) and a 0.9-unit worsening in longitudinal strain (β 0.9; 95% CI: 0.4-1.4; P = 0.001). GDF-15 was not associated with diastolic outcomes, incident diastolic dysfunction, or incident cancer therapy-related cardiac dysfunction. In women receiving anthracycline- and/or trastuzumab-based breast cancer therapy, early increases in GDF-15 were associated with modest declines in left ventricular ejection fraction and worsening of longitudinal strain, without associations with diastolic measures. These findings support mechanistic investigation of GDF-15 in anthracycline-related cardiotoxicity. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341).

To assess the current state of Department of War (DoW)-funded women's health research by analyzing the distribution of funded projects across major clinical and scientific domains for years 2018-2025. Portfolio analysis of DoW Women's Health Research-funded projects categorized by topic area. A narrative synthesis was conducted to characterize funding distribution, identify dominant research domains, and highlight gaps. DOW-funded research demonstrates substantial investment in several domains, with the largest funding concentration in cancer research ($118.5M), followed by reproductive and gynecological health ($19.2M) and musculoskeletal conditions (14.4M). Additional domains include menopause, mental health, and sex-based biological differences. Several areas-including cardiovascular disease, autoimmune disorders, and pain-show minimal or no recorded funding in this dataset. The portfolio reflects a strong emphasis on disease-specific and reproductive health topics, with comparatively limited investment in acute and chronic disease and implementation science. DoW-funded women's health research is concentrated in a small number of domains, particularly cancer and reproductive health. Significant gaps exist, suggesting opportunities for strategic expansion to better align with the evolving health needs of women service members.

Triple-negative breast cancer (TNBC) therapy is limited by the poor efficacy of anti-programmed death-ligand 1 (aPD-L1) monotherapy, with dysregulated lipid metabolism in the tumor microenvironment (TME) driving immunosuppression. Herein, a nanoemulsion co-loaded with berberine (BBR) and rhein (RHE) (BBR-RHE-NE), two lipid-modulating bioactives from Dahuang Huanglian Xiexin Decoction, was fabricated to remodel the immunosuppressive TME and boost aPD-L1 efficacy in TNBC. BBR-RHE-NE was characterized with a small droplet size (185.8 ± 0.44 nm), narrow polydispersity (PDI: 0.12 ± 0.02), and good stability. In orthotopic 4T1Fluc TNBC mouse models, BBR-RHE-NE monotherapy inhibited tumor growth, and its combination with aPD-L1 exerted robust synergistic anti-tumor activity. Flow cytometry revealed that BBR-RHE-NE, as a monotherapy or in combination with aPD-L1, enhanced effector immune cell infiltration and reduced immunosuppressive subsets in both tumor tissues and spleens. Lipidomic analysis, Oil Red O staining, and enzymatic assays confirmed BBR-RHE-NE reduced intratumoral lipid droplet accumulation and downregulated intratumoral triacylglycerols and fatty acids (FAs) levels both in vitro and in vivo. Mechanistically, RNA sequencing and functional validation experiments demonstrated that BBR-RHE-NE potentiated aPD-L1 efficacy via PPARγ/FABP4-mediated lipid metabolic remodeling, a process that promoted dendritic cell maturation and was attenuated by the PPARγ agonist GW1929. Moreover, BBR-RHE-NE exhibited excellent biocompatibility with no detectable organ toxicity. Collectively, these findings demonstrate that BBR-RHE-NE effectively remodels the immunosuppressive TME through lipid metabolic reprogramming, offering a promising nanomedicine-based combinatorial strategy to enhance aPD-L1 immunotherapy for TNBC.