المؤلفون: Albert Grinshpun, Douglas Russo, Wen Ma, Ana Verma, Francisco Hermida-Prado, Shira Sherman, Giorgio Gaglia, Sheheryar Kabraji, Gregory Kirkner, Melissa E. Hughes, Nancy U. Lin, Zachary Sandusky, Agostina Nardone, Cristina Guarducci, Quang-De Nguyen, Sandro Santagata, Zsuzsanna Nagy, Rinath Jeselsohn

المصدر: npj Breast Cancer, Vol 10, Iss 1, Pp 1-12 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2374-4677Test

الوصول الحر: https://doaj.org/article/7c7a103652a4404eac1f649798184d56Test

المؤلفون: Xiaoyong Fu, Resel Pereira, Chia-Chia Liu, Carmine De Angelis, Martin J. Shea, Sarmistha Nanda, Lanfang Qin, Tamika Mitchell, Maria L. Cataldo, Jamunarani Veeraraghavan, Vidyalakshmi Sethunath, Mario Giuliano, Carolina Gutierrez, Balázs Győrffy, Meghana V. Trivedi, Ofir Cohen, Nikhil Wagle, Agostina Nardone, Rinath Jeselsohn, Mothaffar F. Rimawi, C. Kent Osborne, Rachel Schiff

المصدر: Cell Reports, Vol 42, Iss 8, Pp 112821- (2023)

مصطلحات موضوعية: CP: Cancer, Biology (General), QH301-705.5

الوصف: Summary: Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near Secretome14 genes is also increased in mutant ER-expressing or mitogen-treated ER+ BC cells and in ER+ metastatic vs. primary tumors, suggesting a convergent pathway including high growth factor receptor signaling in activating pro-metastatic secretome genes. Our findings uncover H-FOXA1-induced ER reprogramming that drives EndoR and metastasis partly via an H-FOXA1/ER-dependent secretome.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S221112472300832XTest; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/9ae29d74241a427e80d1e8022dc30c52Test

المؤلفون: Arturo B. Ramirez, Raksha Bhat, Debashish Sahay, Carmine De Angelis, Hariprasad Thangavel, Sina Hedayatpour, Lacey E. Dobrolecki, Agostina Nardone, Mario Giuliano, Chandandeep Nagi, Mothaffar Rimawi, C. Kent Osborne, Michael T. Lewis, Jackie L. Stilwell, Eric P. Kaldjian, Rachel Schiff, Meghana V. Trivedi

المصدر: BMC Cancer, Vol 19, Iss 1, Pp 1-10 (2019)

مصطلحات موضوعية: Breast cancer, Circulating tumor cells, Single-cell analysis, Patient-derived xenografts, Chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Breast cancer patient-derived xenograft (BC-PDX) models represent a continuous and reproducible source of circulating tumor cells (CTCs) for studying their role in tumor biology and metastasis. We have previously shown the utility of BC-PDX models in the study of CTCs by immunohistochemistry (IHC) on serial paraffin sections and manual microscopic identification of cytokeratin-positive cells, a method that is both low-throughput and labor-intensive. We therefore aimed to identify and characterize CTCs from small volume mouse blood samples and examined its practical workflow in a study of BC-PDX mice treated with chemotherapy using an automated imaging platform, the AccuCyte®–CyteFinder® system. Methods CTC analysis was conducted using blood from non-tumor bearing SCID/Beige mice spiked with human breast cancer cells, BC-PDX-bearing mice, and BC-PDX mice treated with vehicle or chemotherapeutic agent(s). After red blood cell lysis, nucleated cells were mixed with transfer solution, processed onto microscope slides, and stained by immunofluorescence. The CyteFinder automated scanning microscope was used to identify CTCs, defined as nucleated cells that were human cytokeratin-positive, and mouse CD45-negative. Disaggregated primary BC-PDX tumors and lung metastatic nodules were processed using the same immunostaining protocol. Collective expression of breast cancer cell surface markers (EpCAM, EGFR, and HER2) using a cocktail of target-specific antibodies was assessed. CTCs and disaggregated tumor cells were individually retrieved from slides using the CytePicker® module for sequence analysis of a BC-PDX tumor-specific PIK3CA mutation. Results The recovery rate of human cancer cells spiked into murine blood was 83 ± 12%. CTC detection was not significantly different from the IHC method. One-third of CTCs did not stain positive for cell surface markers. A PIK3CA T1035A mutation present in a BC-PDX tumor was confirmed in isolated single CTCs and cells from dissociated metastatic nodules after whole genome amplification and sequencing. CTC evaluation could be simply implemented into a preclinical PDX therapeutic study setting with substantial improvements in workflow over the IHC method. Conclusions Analysis of small volume blood samples from BC-PDX-bearing mice using the AccuCyte–CyteFinder system allows investigation of the role of CTCs in tumor biology and metastasis independent of surface marker expression.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12885-019-5382-1Test; https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/cda25575e8d7448795627f419d53ae17Test

المؤلفون: Hariprasad Thangavel, Carmine De Angelis, Suhas Vasaikar, Raksha Bhat, Mohit Kumar Jolly, Chandandeep Nagi, Chad J. Creighton, Fengju Chen, Lacey E. Dobrolecki, Jason T. George, Tanya Kumar, Noor Mazin Abdulkareem, Sufeng Mao, Agostina Nardone, Mothaffar Rimawi, C. Kent Osborne, Michael T. Lewis, Herbert Levine, Bing Zhang, Rachel Schiff, Mario Giuliano, Meghana V. Trivedi

المصدر: Journal of Clinical Medicine, Vol 8, Iss 11, p 1772 (2019)

مصطلحات موضوعية: circulating tumor cells, ctc clusters, triple-negative breast cancer, patient-derived xenograft, rppa, transcriptomics, b-cell lymphoma 2, apoptosis, Medicine

الوصف: Circulating tumor cell clusters (CTCcl) have a higher metastatic potential compared to single CTCs and predict long-term outcomes in breast cancer (BC) patients. Because of the rarity of CTCcls, molecular characterization of primary tumors that give rise to CTCcl hold significant promise for better diagnosis and target discovery to combat metastatic BC. In our study, we utilized the reverse-phase protein array (RPPA) and transcriptomic (RNA-Seq) data of 10 triple-negative BC patient-derived xenograft (TNBC PDX) transplantable models with CTCs and evaluated expression of upregulated candidate protein Bcl2 (B-cell lymphoma 2) by immunohistochemistry (IHC). The sample-set consisted of six CTCcl-negative (CTCcl−) and four CTCcl-positive (CTCcl+) models. We analyzed the RPPA and transcriptomic profiles of CTCcl− and CTCcl+ TNBC PDX models. In addition, we derived a CTCcl-specific gene signature for testing if it predicted outcomes using a publicly available dataset from 360 patients with basal-like BC. The RPPA analysis of CTCcl+ vs. CTCcl− TNBC PDX tumors revealed elevated expression of Bcl2 (false discovery rate (FDR) < 0.0001, fold change (FC) = 3.5) and reduced acetyl coenzyme A carboxylase-1 (ACC1) (FDR = 0.0005, FC = 0.3) in CTCcl+ compared to CTCcl− tumors. Genome-wide transcriptomic analysis of CTCcl+ vs. CTCcl− tumors revealed 549 differentially expressed genes associated with the presence of CTCcls. Apoptosis was one of the significantly downregulated pathways (normalized enrichment score (NES) = −1.69; FDR < 0.05) in TNBC PDX tumors associated with CTCcl positivity. Two out of four CTCcl+ TNBC PDX primary tumors had high Bcl2 expression by IHC (H-score > 34); whereas, only one of six CTCcl− TNBC PDX primary tumors met this criterion. Evaluation of epithelial-mesenchymal transition (EMT)-specific signature did not show significant differences between CTCcl+ and CTCcl− tumors. However, a gene signature associated with the presence of CTCcls in TNBC PDX models was associated with worse relapse-free survival in the publicly available dataset from 360 patients with basal-like BC. In summary, we identified the multigene signature of primary PDX tumors associated with the presence of CTCcls. Evaluation of additional TNBC PDX models and patients can further illuminate cellular and molecular pathways facilitating CTCcl formation.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2077-0383/8/11/1772Test; https://doaj.org/toc/2077-0383Test

الوصول الحر: https://doaj.org/article/d8701f5db2c14c9da8230cc0d4baf25dTest

المؤلفون: Nagireddy Putluri, Suman Maity, Ramakrishna Kommagani, Chad J. Creighton, Vasanta Putluri, Fengju Chen, Sarmishta Nanda, Salil Kumar Bhowmik, Atsushi Terunuma, Tiffany Dorsey, Agostina Nardone, Xiaoyong Fu, Chad Shaw, Tapasree Roy Sarkar, Rachel Schiff, John P. Lydon, Bert W. O’Malley, Stefan Ambs, Gokul M. Das, George Michailidis, Arun Sreekumar

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 5, Pp 390-402 (2014)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2–enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S147655861400061XTest; https://doaj.org/toc/1476-5586Test

الوصول الحر: https://doaj.org/article/73ffcf9c2f0a43e69ef35d2b0b955497Test

المؤلفون: Yu-Chen Cheng, Shayna Stein, Agostina Nardone, Weihan Liu, Wen Ma, Gabriella Cohen, Cristina Guarducci, Thomas O. McDonald, Rinath Jeselsohn, Franziska Michor

مصطلحات موضوعية: Cancer, Tumor Biology, Molecular and Cellular Biology, Therapeutic Research and Development, Methods and Technology, Computational Methods, Mathematical modeling, Tumor Evolution, Breast Cancer, Small Molecule Agents, Endocrinology, Hormone signaling and inhibitors, Cell Cycle, CDKs and CDK inhibitors

الوصف: Supplementary Table S3 shows ratio of each schedule to the standard schedule at day 100 for simulated cell lines

العلاقة: https://figshare.com/articles/journal_contribution/Supplementary_Table_S3_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574045Test

الإتاحة: https://doi.org/10.1158/2767-9764.24574045.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Table_S3_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574045Test

المؤلفون: Yu-Chen Cheng, Shayna Stein, Agostina Nardone, Weihan Liu, Wen Ma, Gabriella Cohen, Cristina Guarducci, Thomas O. McDonald, Rinath Jeselsohn, Franziska Michor

مصطلحات موضوعية: Cancer, Tumor Biology, Molecular and Cellular Biology, Therapeutic Research and Development, Methods and Technology, Computational Methods, Mathematical modeling, Tumor Evolution, Breast Cancer, Small Molecule Agents, Endocrinology, Hormone signaling and inhibitors, Cell Cycle, CDKs and CDK inhibitors

الوصف: Supplementary Fig. S4 shows using LOOIC to determine number of stages m

العلاقة: https://figshare.com/articles/journal_contribution/Supplementary_Fig_S4_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574069Test

الإتاحة: https://doi.org/10.1158/2767-9764.24574069.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Fig_S4_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574069Test

المؤلفون: Yu-Chen Cheng, Shayna Stein, Agostina Nardone, Weihan Liu, Wen Ma, Gabriella Cohen, Cristina Guarducci, Thomas O. McDonald, Rinath Jeselsohn, Franziska Michor

مصطلحات موضوعية: Cancer, Tumor Biology, Molecular and Cellular Biology, Therapeutic Research and Development, Methods and Technology, Computational Methods, Mathematical modeling, Tumor Evolution, Breast Cancer, Small Molecule Agents, Endocrinology, Hormone signaling and inhibitors, Cell Cycle, CDKs and CDK inhibitors

الوصف: Supplementary Appendix S2 shows Bayesian estimation of model parameters

العلاقة: https://figshare.com/articles/journal_contribution/Supplementary_Appendix_S2_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574105Test

الإتاحة: https://doi.org/10.1158/2767-9764.24574105.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Appendix_S2_from_Mathematical_Modeling_Identifies_Optimum_Palbociclib-fulvestrant_Dose_Administration_Schedules_for_the_Treatment_of_Patients_with_Estrogen_Receptor_positive_Breast_Cancer/24574105Test

المؤلفون: Cristina Guarducci, Simona Cristea, Avery Feit, Sergey Naumenko, Agostina Nardone, Wen Ma, Douglas Russo, Gabriella Cohen Feit, Ariel Feiglin, Francisco Hermida-Prado, Shira Sherman, Myles Brown, Franziska Michor, Rinath Jeselsohn

المصدر: Cancer Research. 83:GS3-07

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Background Despite the remarkable activity of CDK4/6 inhibitors (CDK4/6i) in the treatment of estrogen receptor positive (ER+) metastatic breast cancer (BC), most patients eventually develop resistance to these drugs. The ctDNA analysis of the PALOMA-3 trial showed that the estrogen receptor (ER) mutation Y537S is a potential mechanism of acquired resistance to the combination of endocrine therapy (ET) with CDK4/6i. To date, the role of the ER mutations in the clonal evolution and the mechanisms of acquired resistance to CDK4/6i is unknown. Moreover, it is not known if the development of resistance to CDK4/6i in the presence or absence of ER mutations is due to the expansion of pre-existing resistant clones or to the de novo acquisition of resistance mechanisms. Methods To explore the clonal evolution and the mechanisms of resistance to CDK4/6i in ER-wild type (ER-WT) and ER-mutant (ER-Mut) BC, we transduced doxycycline (DOX)-inducible Y537S ER-Mut MCF7 cells with the ClonTracer library, a high-complexity DNA barcode library, and cultured the barcoded cells without DOX (MCF7), or with DOX to induce the expression of the Y537S ER mutation (MCF7-YS). To develop Palbociclib (Palbo)-resistant (PDR) and Abemaciclib (Abema)-resistant (ABR) cell models, the barcoded MCF7 and MCF7-YS cells were passaged in culture with increasing concentrations of Palbo and Abema until the acquisition of resistance. The clonal dynamics and the molecular characteristics of the PDR and ABR models were investigated by barcode sequencing, whole-exome sequencing (WES), bulk and single cell RNA sequencing (RNAseq) and protein analyses. Finally, using an ER-Mut barcoded mice model, we compared the in vitro clonal evolution of ER-Mut CDK4/6i-resistant cells with the in vivo clonal evolution of ER-Mut metastases. Results The analysis of the barcodes revealed that during the acquisition of resistance to either Palbo or Abema there is a strong clonal selection of pre-existing resistant clones. The PDR clones were different in the presence of the Y537S mutation versus WT-ER. In contrast, the clones enriched in the ABR cells were comparable between WT and mutant ER. Furthermore, the ER mutations led to decreased diversity of the enriched clones in the PDR but not in the ABR cells. Interestingly, the barcodes enriched in the PDR and ABR models did not overlap. Unsupervised analyses showed that the samples clustering based on the barcodes fractions and the mutations were similar, suggesting that the clonal selection was driven by cellular populations with specific mutational landscapes. All the ER-WT and ER-Mut resistant models had different transcriptional profiles and by single-cell RNAseq showed various degrees of intra-sample heterogeneity. At the protein level, the PDR and the ABR cells displayed downregulation of ER, Rb and p27 and upregulation of p21. In the ER-Mut conditions Cyclin D1 was upregulated in the PDR cells, while Cyclin E was upregulated in the ABR cells. Finally, the barcode sequencing of the mice metastases revealed that the clonal selection in ER-Mut metastases and in ER-Mut CDK4/6i-resistant cells is different. Conclusion Our study suggests that the development of resistance to CDK4/6i is due to the selection of pre-existing resistant clones. We also demonstrate that the expression of the Y537S ER mutation impacts the clonal evolution and the mechanisms of acquired resistance to Palbo but not to Abema. Finally, we show that the clonal evolution and mechanisms are disparate in Palbo and Abema resistance. These results support the addition of a third drug to CDK4/6i and ET, early in treatment, to delay the selection of pre-existing resistant clones and prolong the response to treatment and highlight differences between Palbo and Abema. Citation Format: Cristina Guarducci, Simona Cristea, Avery Feit, Sergey Naumenko, Agostina Nardone, Wen Ma, Douglas Russo, Gabriella Cohen Feit, Ariel Feiglin, Francisco Hermida-Prado, Shira Sherman, Myles Brown, Franziska Michor, Rinath Jeselsohn. GS3-07 Clonal evolution and mechanisms of acquired resistance to CDK4/6 inhibitors in ER-wild type and ER-mutant breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-07.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::db8d5a2fcd983f93aa03bb004d3f5efeTest
https://doi.org/10.1158/1538-7445.sabcs22-gs3-07Test

المؤلفون: Junko Tsuji, Tianyu Li, Albert Grinshpun, Tim Coorens, Douglas Russo, Leilani Anderson, Rebecca Rees, Agostina Nardone, Candace Patterson, Niall J. Lennon, Carrie Cibulskis, Ignaty Leshchiner, Nabihah Tayob, Sara M. Tolaney, Nadine Tung, Donald P. McDonnell, Ian E. Krop, Eric P. Winer, Chip Stewart, Gad Getz, Rinath Jeselsohn

المصدر: Clin Cancer Res

مصطلحات موضوعية: Cancer Research, Treatment Outcome, Receptors, Estrogen, Oncology, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols, Exome Sequencing, Liquid Biopsy, Humans, Female, Breast Neoplasms, Article

الوصف: Purpose: Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated. Patients and Methods: We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2− advanced breast cancer who progressed on prior ET (N = 36; NCT02448771). Results: The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0–7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5–13; P = 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES; N = 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment. Conclusions: The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2− breast cancer. These results merit continued investigation of bazedoxifene in breast cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da4a380680b3c39ba86a4b9cb2d2845eTest
https://doi.org/10.1158/1078-0432.ccr-22-2305Test