ER positive

P2/3, N=849, Active, not recruiting, Immutep S.A.S. | Recruiting --> Active, not recruiting

Five-profile classification provides a more accurate idea about the rate of potential change in treating BC in the metastatic setting.

The Random Forest classifier emerged as the top performer, achieving an AUC of 0.95 and an accuracy of 93%. These results suggest that ML has great promise for identifying specific metabolites linked to ER expression, paving the development of a novel analytical tool that can minimize current challenges in identifying ER status, and improve the precision of breast cancer subtyping.

This review describes how sex steroid hormones, particularly estrogens and androgens, affect stromal cells in the breast cancer microenvironment. We summarize recent findings focusing on the effects of ER/AR signaling in breast cancer cells on stromal cells, as well as the direct effects of ER/AR signaling in stromal cells.

Adjusting treatment strategies based on BMI across different menopausal statuses and tumor subtypes could improve outcome for patients with ER-positive/PR-positive tumors.

We tested whether this HR dysfunction could indeed be exploited using PARP inhibition and found that talazoparib treatment produced a durable growth suppression in vitro and in multiple ILC xenografts in vivo...ILC are rarely associated with biomarkers of HR deficiency, and as such patients are rarely eligible for treatment with PARP inhibitors. Our work suggests ILC present with a previously unappreciated form of HR dysfunction, linked to ILC-specific genomic activity of ER and MDC1, which imparts sensitivity to PARP inhibition.

P3, N=812, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2032 --> Dec 2030 | Trial primary completion date: Aug 2026 --> Mar 2027

Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged ≥ 65 years with low-risk, ER-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.

Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028

However, results were based on few distinct study populations and generally had low precision, underscoring the need for replication. In conclusion, prostate cancer with TMPRSS2:ERG fusion is an etiologically distinct subtype that may be, in part, preventable by addressing modifiable and hormonally acting etiologic factors that align with the established mechanistic role of TMPRSS2:ERG in androgen, insulin, antioxidant, and growth factor pathways.

Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).

These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned.

SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynaecologic carcinoma, a potential diagnostic pitfall. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations, without specific genetic underpinnings identified. Additional studies are warranted to further evaluate the clinical behaviour of these tumours.

Neither ERG-positive nor PTEN loss were associated with upgrading during AS. ERG and PTEN biomarkers, despite commonly studied in advanced PCa, have yet no defined role in very low-risk PCa under AS. PI-RADS score was an independent predictor of GS upgrading and extreme upgrading during AS.

LicA targets SREBP1, a central regulator of lipogenesis and immune response, reducing pro-tumorigenic aberrations in lipid homeostasis and inflammation. It is a promising non-endocrine candidate for BC prevention.

Therefore, we suggest that there is an underappreciated association between the HER2-low subtype and endocrine resistance. In this perspective piece, we explore the evidence linking the HER2-low subtype with the various pathways to endocrine resistance and suggest that there are signaling networks in HER2-low tumors that intersect endocrine resistance and can be effectively targeted.

Considering the estrogen receptor positive invasive breast cancer of no special type cases, we showed that TSR had a positive prognostic value with an optimal threshold of 10 %. This study is one of the first to show inverse correlations between tumoural stroma amount and intra- and peritumoural lymphocyte percentages, which supports the hypothesis that tumoural stroma can prevent the recruitment of lymphocytes around and within the tumour.

These results suggest that, compared with continuing consumption, alcohol cessation may reduce ER + but not ER- breast cancer risk. However, research that considers duration of cessation is warranted.

P2, N=169, Completed, Melissa K Accordino | Active, not recruiting --> Completed

Given low rates of genomic testing uptake nationally, image-based methods may help identify ER+/HER2-patients who could benefit from testing.

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.

P2, N=65, Active, not recruiting, Jules Bordet Institute | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2024 --> Jan 2025

Mechanistically, increased p110α levels result from inhibited degradation by E3 ubiquitin ligase NEDD4L. These findings suggest N6AMT1 as a potential luminal breast cancer biomarker and highlight the N6AMT1-p110α pathway as a therapeutic target to sensitize cells to tamoxifen.

Black patients face more frequent delays throughout the care continuum, likely stemming from different types of access barriers at key junctures. Improving breast cancer care access will require intervention on multiple aspects of SES and healthcare access.

Further, IGFBP-3 expression was increased by treatment with the GPER1 agonist G-1 and attenuated upon treatment with P17, a YAP/TAZ inhibitor. These data suggest that IGFBP-3 modulates breast cancer cells and is a mediator of breast cancer cell response to fulvestrant and tamoxifen.

We term this method SAM-DNMT3A and show that induction of global DNA methylation is a unique vulnerability in ER-positive breast cancer suggesting a therapeutic approach. Our findings highlight the need of caution when using CRISPR based approaches for inducing DNA methylation and demonstrate a method for global induction of DNA methylation.

P2, N=333, Completed, Queen Mary University of London | Unknown status --> Completed

P1, N=214, Active, not recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting

P=N/A, N=45, Not yet recruiting, Monash University

Racial/ethnic differences exist in ductal carcinoma in situ tumor biology and treatment, both of which may contribute to poorer outcomes in disparate groups.

A total of 94% of patients >74 years with T1a/b, ER positive HER2 negative breast cancer were node negative. Nodal status significantly influences adjuvant treatment in this patient group and therefore, we recommend clinicians consider tumour factors and patient fitness in their decision making about SLN biopsy in the elderly population with hormone receptor positive early breast cancer.

Based on real-world data analysis, in ER-positive, HER2-negative post-menopausal women with early breast cancer in Taiwan, the use of tamoxifen compared to AIs is associated with a lower risk of recurrence. Improved adherence to medication can break the cycle of recurrence and improve health outcomes.

The epithelial alternatively spliced FGFR2 IIIb isoform was significantly enriched in ER+ breast cancer, while the mesenchymal FGFR2 IIIc isoform was significantly prevalent in HER2+ cancer. Increased levels of FGFR2 and IIIb splice isoforms are associated with less aggressive breast cancer phenotypes, while decreased levels of FGFR2 and increased IIIc splice isoform are associated with more aggressive phenotypes.

Using proximity ligation assays, we showed that VPC-260724 disrupts the interaction between ER-AF2 and the coactivator SRC-3 and reduces the expression of ER target genes in various breast cancer models including the tamoxifen resistant cell line TamR3. In conclusion, we developed a novel ER-AF2 binder, VPC-260724, which shows antiproliferative activity in ER-positive breast cancer models. The use of an ER-AF2 inhibitor in combination with current treatments may provide a novel complementary therapeutic approach to target treatment resistance in ER-positive breast cancer.

LTP in layer 4 to layer 2/3 synapses in the somatosensory cortex was also reduced in slices from letrozole-treated mice, showing deficits in structural and functional plasticity resulting from aromatase inhibition. Ovariectomized mice performed worse than intact control mice in the novel object recognition test but, surprisingly, letrozole treatment rescued this deficit.

We provide the evidence that CDK4/6 inhibitor LY2835219 plus BRD4 inhibitor OTX-015 synergistically inhibits both ER positive and triple-negative breast cancer cells growth in vitro and in vivo. This instability of BRD4 protein in turn enhances the anti-tumor effect of CDK4/6 inhibitor by suppressing transcription of DNA damage repair gene RAD51, and synergistically promotes γ-H2AX accumulation and DNA double-strand breaks. Overall, we demonstrated the potential combined therapeutic value of CDK4/6 and BRD4 inhibitors and elucidated the mechanisms, which may provide a new rational approach for breast cancer patients.

Phenotypic analysis of macrophages cocultured with T47D cancer cells following S100A11 knockdown revealed lower expression of the immunosuppressive marker CD206, further underscoring the role of S100A11 as a paracrine regulator of pro-tumorigenic cancer-macrophage crosstalk. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.

Our study suggests that RS results can refine treatment decisions for patients with EBC exhibiting uncertain biological behavior initially recommended or considered for CT. (250/250).

ERD-12310A achieved a DC50 value of 47 pM and is 10 times more potent than ARV-471...Importantly, ERD-12310A achieved strong tumor growth inhibition in MCF-7 xenograft tumors harboring the clinically relevant ESR1Y537S mutation, which confers resistance to traditional antiestrogens. Our data position ERD-12310A as a promising candidate for further development as a potential therapy for ER+ breast cancer.