Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Differential effects of oral contraceptives on lymph node metastasis in breast cancer: role of tumor size as an effect modifier.","authors":"Yang Saimei, Su Qiu, Xie Baodong","doi":"10.1007/s10911-026-09615-w","DOIUrl":"10.1007/s10911-026-09615-w","url":null,"abstract":"<p><strong>Objective: </strong>Lymph node metastasis (LNM) is a critical determinant of breast cancer prognosis. While oral contraceptives (OC) are associated with breast cancer risk, their relationship with LNM-particularly in understudied populations like Morocco-remains unclear. This study investigates whether tumor size modifies OC-LNM associations in Moroccan patients.</p><p><strong>Methods: </strong>We analyzed 356 breast cancer cases from Morocco's National Institute of Oncology(2009). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for OC-LNM associations were estimated using multivariable logistic regression, stratified by tumor size (≤ 2 cm vs. > 2 cm). Multiplicative and additive interactions between OC use and tumor size were assessed.</p><p><strong>Results: </strong>After full adjustment for clinicopathological factors, OCs use was associated with reduced LNM risk in tumors ≤ 2 cm (OR = 0.08, 95% CI: 0.02-0.47, P = 0.005) but increased risk in tumors > 2 cm (OR = 1.97, 95%CI: 1.04-3.76, P = 0.039). Significant multiplicative interaction (P = 0.047) and evidence of additive interaction (RERI = 1.72, AP = 0.69) suggest tumor size acts as an effect modifier, though the precision of the additive interaction estimate is limited (AP 95% CI: 0.30-1.07).</p><p><strong>Conclusion: </strong>Tumor size critically modifies OC-LNM relationships, with protective effects in small tumors and risk-promoting effects in large tumors. This heterogeneity underscores the need for size-stratified assessments in breast cancer management.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COX-2- and IDO-associated immunomodulatory functions of stage II carcinoma-associated fibroblasts in breast cancer.","authors":"Ladan Langroudi, Zuhair M Hasan, Masoud Soleimani, Seyed Mahmoud Hashemi","doi":"10.1007/s10911-026-09613-y","DOIUrl":"10.1007/s10911-026-09613-y","url":null,"abstract":"<p><p>The immune response against cancer is influenced by the tumor stroma. Carcinoma-associated fibroblasts (CAFs), a significant part of the stroma, are important modulators of the tumour microenvironment (TME). The current study examined the immunomodulatory properties of CAFs isolated from a stage II mouse model of mammary invasive ductal cancer. Based on the expression of surface markers, we described Stage II CAFs and assessed their effects on cytokine release, nitric oxide (NO) generation, and splenocyte proliferation in direct co-culture systems. Class II MHC molecules (I-Ad/I-Ed), FAP-1, CD29, CD90, and CD105 were all expressed by isolated CAFs, indicating the possibility of direct immunological contact. In direct co-culture, CAFs demonstrated two distinct functions: their conditioned medium (CM) had immunosuppressive effects, whereas direct cell interactions promoted splenocyte growth. Additionally, CAFs changed the cytokine milieu, particularly by secreting high levels of TGF-β and PGE₂, and dramatically reduced splenocyte NO generation. COX-2, IDO, and MMP2 were significantly upregulated in CAFs, according to gene expression data. Our results emphasize the potential of Stage II CAFs as a therapeutic target in breast cancer by demonstrating their complex immunomodulatory character, which includes the ability to both stimulate and repress immune responses through cellular contact and soluble factors.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preserving RNA quality when freezing of human milk samples must occur before extraction: Validation of methods utilized in a multi-center cohort study.","authors":"Haijing Sun, Margaret Rabotnick, Sofia Nicastro, Daniel Robinson, Jami Josefson, Karyna Caal, Aika Noguchi, Lindsay Ellsworth, Dave Bridges, Brigid Gregg","doi":"10.1007/s10911-026-09611-0","DOIUrl":"10.1007/s10911-026-09611-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Recent multicenter studies aim to define the effects of mothers' blood glucose levels during pregnancy on mammary gland function and breast milk composition. Gene expression measured in cells in milk can serve as a liquid biopsy to evaluate the molecular biology of the mammary gland. Critical to this aim is reproducible and high-quality extraction of RNA from milk and harmonized collection protocols from across centers. To address this, we performed a study to optimize milk RNA quality metrics where samples are collected at multiple centers and shipped to a central laboratory for processing and analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Lactating mothers provided breast milk following informed consent. The treatments of the samples were as follows: (1) 200 µL of fresh, never frozen milk used as control (FRESH); (2) 1.7 or 5 mL of milk frozen and thawed on ice before adding TRIzol (FRZ); (3) 200 µL of milk frozen and thawed after adding TRIzol (FRZ 200); and (4) 200 µL of milk with 20 µL of RNA preservative added, frozen and thawed after adding TRIzol (FRZ + INH). In all scenarios, RNA was extracted using TRIzol followed by purification with a Qiagen RNeasy Mini kit. For the FRZ 200 and FRZ 200 + INH samples, TRIzol was directly added at the start of thawing, before extraction. Outcomes included RNA concentration, RNA purity (260/280 ratio), RNA fragmentation (DV 200), RNA integrity number (RIN), quantification via Qubit fluorescence-based assays, and visualization of RNA size on an Agilent TapeStation. A RIN cut-off value ≥ 7 indicated acceptable quality for transcriptomics studies. RNA quality metrics were modeled as continuous outcomes using linear mixed-effects regression models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;For FRESH milk (n = 15) the estimated marginal mean (EMM) RIN was 7.48 (SE 0.29). For FRZ 200, (n = 22), the EMM RIN was 6.94 (SE 0.26). Samples of FRZ 200 + INH (n = 21) had an EMM RIN of 7.81 (SE 0.26). However, FRZ (n = 19) samples demonstrated markedly reduced RNA integrity with an EMM RIN of 1.92 (SE 0.26). RIN was not significantly different in FRESH versus FRZ 200 or FRZ 200 + INH milk. FRZ 200 + INH samples showed a statistically significant improvement in RIN compared to FRZ 200 (p = 0.0038). RNA quantities were sufficient for sequencing across all treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The addition of TRIzol directly to a 200 µL aliquot of milk at the start of thawing provided the highest integrity of extracted milk RNA, as measured by RIN. Adding RNase inhibitor at the time of sample collection, prior to freezing, also enhanced RNA integrity. We have developed a method to optimize the integrity of RNA from frozen human milk samples. This is a crucial methods improvement for multi-center studies where freezing of milk samples is often required prior to RNA extraction and analysis. These results can inform reproducible research protocols for evaluating the use of breastmilk as a liquid bi","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Model of Milking Pulses and Stretching Cycles: Assessing Mechanical Effects on Bovine Mammary Cells.","authors":"Guy Dabby, Yael German, Liron Nomi Toledano, Nir Zaharoni, Enav Bar-Shira, Eduard Belausov, Yifat Brill-Karniely","doi":"10.1007/s10911-026-09610-1","DOIUrl":"10.1007/s10911-026-09610-1","url":null,"abstract":"<p><p>Culture models of mammary glands can be significantly enhanced by simulating physical forces, including those experienced by the tissue during milking or nursing. In particular, in vitro biophysical studies of bovine mammary cells can provide novel insights into the effects of milking pulses on cellular function, which are currently not well understood. We introduce here a system for modeling uniaxial stretching cycles in culture such as those exerted by vacuum pulses during milking. Bovine mammary epithelial cells (MECs) were cultured under several conditions in stretchable silicone chambers and monitored before and after applying various protocols of stretching pulses. Image processing was conducted for detailed analysis of thousands of MECs in each condition. In the stretchable chambers and upon stretching pulses the bovine MECs maintained high viability, normal proliferation and expression of fat globules, indicating that this system is suitable for tracing functional aspects. We demonstrated usage of the stretching pulses methodology in two possible fields of interest. The first is the fundamental study of the reaction of isolated bovine MECs to stretching cycles, in which we observed cell rounding under various stretching protocols, while maintaining surface adherence and high viability. In the second branch we imitated physiological conditions of mammary epithelium under milking pulses and found that morphological homeostasis was maintained as well as high production of lipid globules with preserved size distribution. Furthermore, our analysis suggests that in collagen-coated chambers and differentiation medium, milking pulses enhance the extracellular release of fat globules. Collectively, the data in this section reflected the ability of mammary epithelium to maintain structural integrity, function effectively, and potentially enhance functionality under milking pulses.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Looking in the Rear-View Mirror: How Lineage Tracing Experiments Redefined Cell Hierarchy in the Mammary Gland.","authors":"Alexandra Van Keymeulen","doi":"10.1007/s10911-026-09609-8","DOIUrl":"10.1007/s10911-026-09609-8","url":null,"abstract":"<p><p>Understanding the cell hierarchy of the mammary gland has been a major focus of research for several decades. This review retraces the key advances enabled by lineage tracing approaches to study stem cells and cell hierarchy in the mammary gland. Although not exhaustive, this review highlights the paradigm shifts brought about by lineage tracing studies, which have, in the author's view, profoundly reshaped our understanding of mammary epithelial organization. In particular, these studies have challenged traditional models of cell hierarchy and the concept of terminally differentiated cells in the mammary gland.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Estrogen Receptor Alpha and Ki-67 in Synchronous Canine Mammary Tumors.","authors":"Nina Hansen, Ingrid M Moberg, Monica Hongrø Solbakken, Gjermund Gunnes, Kaja Sverdrup Borge, Ellen Frøysadal Arnet, Ole Albert Guttersrud, Helga Bergholtz, Frode Lingaas","doi":"10.1007/s10911-026-09608-9","DOIUrl":"10.1007/s10911-026-09608-9","url":null,"abstract":"<p><p>Mammary tumors are the most common cancer in female dogs. Many dogs develop synchronous tumors, i.e. tumors occurring simultaneously or within a short time period in the same or different mammary gland. Whether synchronous canine mammary tumors are more biologically similar than random tumors due to shared genetic and environmental factors remains uncertain. Estrogen receptor alpha (ER) and Ki-67 are important biomarkers in human breast cancer but less studied in canine mammary tumors (CMTs). To assess tumor similarity and intratumoral heterogeneity, this study examined ER and Ki-67 expression in 72 synchronous CMTs from 36 dogs using immunohistochemistry (IHC), and the expression of the PAM50 gene set in a subset of tumors. Across all tumors, benign tumors exhibited higher ER Allred scores, whereas malignant tumors had higher Ki-67 indices. Malignant tumors displayed greater intratumoral Ki-67 heterogeneity, while intratumoral ER heterogeneity remained consistent across tumor types. For synchronous tumors, Ki-67 index demonstrated moderate to high concordance across most comparisons, with highest concordance in malignant pairs. In contrast, ER Allred score exhibited a moderate similarity only in pairs with identical histopathological diagnosis. Malignant-benign pairs showed poor similarity for both markers. The poorer intradog correlation of the ER Allred score compared to the Ki‑67 index suggests that ER expression is largely tumor‑specific. Analysis of PAM50 gene expression revealed molecular patterns resembling human breast cancer subtypes across the cohort. Expression of PAM50 genes was highly correlated in benign-benign pairs, while variable in pairs with malignant tumors. These findings highlight the complexity of CMTs, emphasizing the need for individualized tumor evaluation and complete tumor removal in dogs with multiple tumors.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13260167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A-to-I RNA Editing Endows miR-3664-5p with Carcinogenicity in Breast Cancer Through Modulating LONP2 Mediated Glycolysis.","authors":"Yajing Han, Xueli Wei, Xuesen Zhang, Jianjun Wu, Fan Wang","doi":"10.1007/s10911-026-09602-1","DOIUrl":"10.1007/s10911-026-09602-1","url":null,"abstract":"<p><p>Breast cancer has become the main cause threatening women's health. RNA editing is one of the most important mechanisms for modifying genetic information. This study explained the relationship between A-to-I RNA edited miR-3664-5p and malignant phenotype of breast cancer. The results showed that high editing level of miR-3664-5p in breast cancer, which was related to tumor stage, recurrence and prognosis of breast cancer patients. ADAR perturbation experiments demonstrated that ADAR1 is the key enzyme regulating miR-3664-5p editing in breast cancer. A series of in vitro assays revealed that miR-3664-5p functioned as a tumor suppressor in breast cancer, but ed-miR-3664-5p promoted breast cancer development. Mechanically, dual-luciferase reporter assay confirmed that ed-miR-3664-5p directly targets LONP2, yet wt-miR-3664-5p loss this binding site. ChIP assay proved that PKM2 was enriched in the transcriptional regulatory region of LONP2 gene. Seahorse XFe analysis showed that LONP2 knockdown strengthened glycolysis in breast cancer. Xenograft assay also demonstrated that edited miR-3664-5p affected glycolysis in breast cancer through the regulation of LONP2. In conclusion, A-to-I RNA editing endows miR-3664-5p with carcinogenicity in breast cancer through modulating LONP2 mediated glycolysis.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular and Genomic Landscape of the Dark Agouti Rat Mammary Adenocarcinoma: Preliminary Insights for Triple-Negative Breast Cancer Modeling.","authors":"Ifeoma J Dikeocha, Adrien Oliva, Emma Bateman, Hannah R Wardill, Joanne M Bowen","doi":"10.1007/s10911-026-09606-x","DOIUrl":"10.1007/s10911-026-09606-x","url":null,"abstract":"<p><p>The isogenic, tumor-bearing Dark Agouti Mammary Adenocarcinoma (DAMA) model is commonly utilized in breast cancer research to evaluate mechanisms of, and interventions for chemotherapy-induced toxicity and tumor response. However, the biological subtype, immune landscape, and genomic profile of DAMA have remained uncharacterized. In this study, we comprehensively evaluated DAMA tumors naïve and exposed to methotrexate, assessing their histopathological, molecular, and genomic features. Our findings reveal that the DAMA model presents a platform to model the human triple-negative breast cancer (TNBC), as it exhibits substantial macrophage infiltration, the tumors display dysregulation of oncogenes Bcl2, Egfr, and potentially Myc, suggesting apoptotic resistance as a key mechanism driving growth. These characteristics position the DAMA model as a potential preclinical model for investigating TNBC biology, therapeutic responses, and drug toxicity.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological Stress Increases the Expression of Milk-Derived miR-210-5p.","authors":"Takeshi Chiba, Miho Fujisawa, Tomoji Maeda","doi":"10.1007/s10911-026-09607-w","DOIUrl":"10.1007/s10911-026-09607-w","url":null,"abstract":"<p><p>Psychological stress during lactation decreases β-casein concentration in milk. Smoking-induced increases in miR-210 expression also decrease β-casein concentration in milk and inhibits its synthesis in mammary epithelial cells. However, the relationship between stress and miR-210 expression in the mammary epithelium has remained uninvestigated. Here, we investigated the association between stress and miR-210-5p (miR-210) expression in the mammary epithelium and evaluated whether miR-210 is involved in stress-induced suppression of β-casein content in breast milk. miR-210 expression in the milk and mammary epithelium of restraint-stressed mice was significantly higher than that in control mice. Additionally, β-casein mRNA expression and the protein levels of signal transducer and activator of transcription 5 (STAT5) and phosphorylated STAT5 were significantly lower than those in control mice. In clinical investigation, a significant positive correlation was observed between miR-210 levels in breast milk and the total mood disturbance (TMD) score determined using the Profile of Mood State 2nd Edition–Adult Short questionnaire. In contrast, the positive mood scale vigor–activity on the TMD subscale and the positive mood scale friendliness exhibited a significant negative correlation with miR-210 levels in breast milk. These results indicate that miR-210 levels in breast milk may be increased in nursing mothers with a strong negative mood. In conclusion, psychological stress during lactation may induce miR-210 expression in the mammary epithelium, resulting in increased miR-210 levels in breast milk. Additionally, stress-induced suppression of β-casein concentration in breast milk might be related to the induction of miR-210 expression in the mammary epithelium.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell RNA-sequencing reveals that testosterone reduces estrogen signaling in the healthy human mammary gland.","authors":"Kiet T Phong, Siyou Song, Esther A Kim, Daniel N Conrad, Zev J Gartner","doi":"10.1007/s10911-026-09605-y","DOIUrl":"10.1007/s10911-026-09605-y","url":null,"abstract":"<p><p>Testosterone is the most studied androgen in hormone replacement therapy in postmenopausal women. Many transgender men also receive long-term testosterone replacement therapy (TRT) and have high serum testosterone levels compared to the low levels seen in cisgender women. Compared to other sex hormones such as estrogen and progesterone, the effects of testosterone on the mammary gland have been relatively understudied and there is little data regarding the long term safety of this treatment. Comparison of mammary glands from transgender men on TRT and cisgender women can reveal the effects of testosterone treatment on mammary gland biology and provide critical information regarding the long-term effects of TRT on patient health and disease outcomes. In this study, we performed single-cell RNA sequencing of breast tissues from a demographics-matched cohort of cisgender women and transgender men on TRT. Participants on TRT had unchanged plasma levels of estradiol compared to controls. However, TRT treatment was associated with dramatically reduced expression of genes downstream of estrogen signaling pathways in hormone receptor positive (HR+) luminal epithelial cells, as well as a decreased overall menstrual cycle-related hormone signaling. We confirmed this finding experimentally by showing reduced expression of progesterone receptor a/b, a prominent marker of estrogen signaling, in donors on TRT. Our results support the hypothesis that high levels of testosterone in transgender men on TRT suppress sex hormone signaling in the breast as seen by their impact on HR+ mammary epithelial cells, with implications for TRT as an antagonist of estrogen signaling and protection against breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}