scholarly journals In vitro validation of the immunogenicity of the predicted neoepitopes from high-risk estrogen receptor-positive breast cancer

2021 ◽  
Author(s):  
Yun-jeong Choe ◽  
Eunyoung Kim ◽  
Jooyeon Oh ◽  
Miran Jang ◽  
Weixan Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Rna Seq ◽  
Lung Cancers ◽  
Luminal B ◽  
Mutation Burden ◽  
Estrogen Receptor Positive ◽  
Ifn Γ ◽  
Donor Pbmcs

Abstract Whether estrogen receptor-positive (ER+) breast cancer (BC) can be a target for therapeutic neoepitope vaccination is not clear due to its low mutation burden. We tested the immunogenicity of predicted neoepitopes from exome and RNA-seq data from three ER+/luminal B subtype BC samples using IFN-γ ELISpot assays of HLA-matched donor PBMCs. As a control, three ER- BC and three lung cancers were tested. The ensemble of Neopepsee and pVACseq pipelines predicted 93 neoepitopes from 299 SNVs in three ER+ BCs. Among them, 90 could be tested with ELISpot, and 14 (15.6%) were immunogenic (1, 5, and 10 for each tumor). In three ER- BC samples, 52 neoepitopes were predicted from 271 SNVs, and 12 (25.0%) of 48 tested were immunogenic (2, 4, and 8 for each tumor). Of the three lung cancers, 53 of 72 predicted neoepitope candidates were tested, and 10 of them were immunogenic (18.9%) (0, 1, and 11 for each tumor). These differences were not statistically significant. We conclude that luminal B subtype BCs express neoepitopes and can be a candidate for therapeutic neoepitope vaccination.

scholarly journals Estrogen receptor regulates hormone-induced growth arrest in a luminal A like breast cancer model

2018 ◽  
Author(s):  
Lacey Haddon ◽  
Sunny Hu ◽  
Hosna Jabbari ◽  
Brittney Loney ◽  
Zelda-Saidman Lichtensztejn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Model ◽  
Dna Looping ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Estrogen Receptor Positive ◽  
Er Expression

Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and luminal B, which differ in their ER expression and response to hormone therapy. The absence of luminal A cell lines means the extensive amount of in vitro work studying the response to hormones in ER+ breast cancers is biased for the luminal B subtype. We have developed a luminal A like cell model by increasing the ER expression in the MCF-7 cell line. Our results show that increased ER expression promotes an anti-proliferative response to estrogen through regulation of genes involved in the G1/S-phase transition of the cell cycle. Furthermore, increased ER expression increases ER-DNA binding in the absence of estrogen and regulates basal gene transcription by promoting DNA looping. These results provide novel evidence that the characteristic increased ER expression of luminal A tumors may promote a novel chromatin configuration that enables growth of these tumors in the absence of estrogen and enables gene repression in the presence of hormones.

scholarly journals Virtual screening of natural compounds as combinatorial agents from indian medicinal plants against estrogen positive breast cancer

2020 ◽  
Vol 3 (10) ◽  
pp. 266-275
Author(s):  
Shaleen Jain ◽  
Dr. Asmita Das
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Virtual Screening ◽  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Common Amino Acid ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Facing worldwide challenges associated with multifactorial etiology of breast cancer, designing of combinatorial therapies using natural compounds is currently the emergent way of treating several cancers including breast cancer in a synergistic way, which may mitigate several problems associated with multiple receptor targeting. In this research, Estrogen receptor positive breast cancer was taken as prototype and several key receptors associated with this particular disease were targeted by virtual screening of natural compounds found in Indian originated medicinal plants using Computer aided Drug Designing (CADD) strategies. We found the combination of Carpusin, Paulownin Cornigerine, Nororientaline, Oryzalexin B, Romucosine H and Colchicine as effective against six potential receptors i.e. FGFR2, ESR1, PIK3CA, PIK3CB, PIK3CD and AR in Estrogen receptor positive breast cancer with their binding energies in the range of ∆G ≤ -8.0 Kcal/mol as well as significant number of common amino acid binding residues as compared with binding sites of receptors. Thus this research holds significant implications for the designing of combinatorial therapeutic agents against breast cancer which can be further tested in-vitro and in-vivo to prove their synergistic efficiency.

scholarly journals Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

2016 ◽  
Vol 34 (17) ◽  
pp. 1987-1994 ◽  
Author(s):  
Peter Schmid ◽  
Sarah E. Pinder ◽  
Duncan Wheatley ◽  
Jane Macaskill ◽  
Charles Zammit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Geometric Mean ◽  
Tumor Cell Proliferation ◽  
Geometric Mean Ratio ◽  
Ki 67 ◽  
Luminal B ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Purpose Preclinical data support a key role for the PI3K pathway in estrogen receptor–positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer.

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