Ratcliffe M, Yaghjyan L, Heng YJ, Baker GM, Rosner BA, Tamimi RM. Associations of alcohol consumption with expression of CD44, CD24, and ALDH1A1 stem cell markers in benign breast biopsy samples. Cancer Causes Control. In Press In Press.
Publications
In Press
Tesch ME, Zheng Y, Guzman-Arocho YD, Collins LC, Heng YJ, Tayob N, Rosenberg SM, Ruddy KJ, Tamimi RM, Schapira L, et al. Association of tumor-infiltrating lymphocyte subtypes with clinical characteristics and prognosis in young women with hormone receptor-positive breast cancer. Clin Cancer Res. In Press In Press.
Oh H, Heng YJ, Baker GM, Sardella BR, Mahoney MR, Murthy D, Rosner B, Tamimi RM, Yaghjyan L. Associations of adiposity and growth measures with the expression of stem cell markers among women with benign breast biopsies in the Nurses’ Health Study II. Br J Cancer. In Press In Press.
Submitted
Wang L, Sardella BR, Thavamani A, Massicott ES, Bret-Mounet VC, Baker GM, Guzman-Arocho YD, Tobias AM, Bartlett RA, Aronson EK, et al. Masculinizing Testosterone Therapy Reduces the Incidence of PIK3CA-Mutant/ER+ Breast Cancer but Not BRCA1-Associated Triple-Negative Breast Cancer. Submitted. Submitted Submitted.
Background We investigated the impact of gender-affirming testosterone therapy (TT) on breast cancer (BC) risk and tumor progression. Materials and methods We leveraged a large human breast tissue dataset (n=417) to assess TT and terminal duct lobular unit (TDLU) involution, complemented with tissue markers (ER, PR, AR, and Ki67; n=24) and transcriptome profiling (n=8). Preclinical models assessed the effect of TT on BC incidence (MMTV-Cre Pik3caf/wt n=149 and K14-Cre Brcaf/fTp53f/f n=153), murine mammary gland architecture (n=60), and tumor transcriptome (n=10). Lastly, we discuss trans masculine invasive BC cases and summarize tumor characteristics in this population (n=24). Results TT promotes TDLU involution by reducing epithelial proliferation via altered estrogen signaling and increases ER+, PR+, and Ki67+ extralobular stromal cells. In mice, TT similarly reduced mammary gland ductal branching and terminal end buds. TT decreased Pik3ca-related ER+ BC incidence by 81% compared to female controls (adj RR 0.19, 95% CI 0.08-0.45), but did not affect Brca1-related triple negative BC incidence. TT did not influence tumor progression in either model but shaped the Pik3ca-related ER+ tumor microenvironment toward a pro-tumor phenotype. Most trans masculine BC cases were ER+ (83.3%), small and node-negative, but were also moderately to poorly differentiated (70.8%). Conclusion TT reduces ER+ BC risk but does not eliminate risk, and has a negligible impact on BRCA1-related triple-negative BC risk. TT does not affect tumor growth once tumors are established but modulates the tumor microenvironment. Our work supports the need for breast cancer screening in TT users.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the National Cancer Institute (NCI) R56CA284564 (YJH and GMW), R21CA267088 (YJH and GMW), R01CA226776 (GMW), P50CA168504 SPORE Career Enhancement Program (YJH), and Columbia Innovation Grant (LCH and KC). GMW is supported by the Breast Cancer Research Foundation 24-177. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the NICHD R24HD102061.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the BIDMC Committee for Clinical Investigations (2018P000814), Columbia University IRB (AAAT0129), and BIDMC IACUC protocol (#052-2020-23). The Dana Farber/Harvard Cancer Center Office for Human Research Studies IRB determined that the medical records review of the four new invasive BC cases meets the criteria for exemption from IRB review (25-223).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesRNASeqdata are available at the National Center for Biotechnology Information Gene Expression Omnibus (GSE306236). All other data that support the findings of this study are available from Dr. Jan Heng.
Wang L, Sardella BR, Aronson EK, Liu Z, Li X, Wulf GM, Heng YJ. Simultaneous Inhibition of PARP/AKT to Intercept Nascent BRCA1/2mut Breast Tumors. Submitted. Submitted Submitted.
Yaghjyan L, Heng YJ, Guzman-Arocho YD, Colditz G, Sardella BR, Fu A, Patel K, Rosner BA, Ratcliff M, Tamimi RM. Reliability of breast stromal markers immunofluorescent staining: pathologist assessment compared to quantitative image analysis. Submitted. Submitted Submitted.
Yaghjyan L, Heng YJ, Sardella BR, Ratcliffe M, Rosner BA, Tamimi RM. Associations of oral contraceptives with expression of CD44, CD24, and ALDH1A1 stem cell markers in women with benign breast biopsies. Submitted. Submitted Submitted.
Tamimi RM, Giulianini F, Peng C, Cook NR, Heng YJ, Bret-Mounet VC, Quintana LM, Buring JE, Manson JE, Fowler E, et al. Changes in mammographic features and breast tissue gene expression associated with moderate-dose vitamin D supplementation. N/A. Submitted Submitted.
2025
Zhao S, Chen Q, Saiding Q, An S, Zhou Z, Heng YJ, Abdi, Tao W. Live bacterial chemistry in biomedicine. Chem. 2025;11(4):102436.
Kelly RL, Liu Y, Harris AR, Peng CK, Heng YJ, Baker GM, Stover DG, Tamimi RM, Kraft P. The breast tumor immune microenvironment of DNA double-strand break repair pathogenic variant carriers is enriched with tumor associated macrophages. Cancer Epidemiol Biomarkers Prev. 2025;34 (6):868–874.