Compounds 1-6 showed a significant aromatase inhibition with IC50 values in the range of 2.01-3.13 μM as compared to the standard drug, exemestane (IC50 = 0.21 ± 0.16 μM)...Moreover, compounds 1-6 were found as non-cytotoxic to BJ (Human fibroblast) normal cell line. Hence, these molecules can be further studied for optimization as potential aromatase inhibitors against breast cancer.

No abstract available

P1, N=53, Completed, Rovi Pharmaceuticals Laboratories | Active, not recruiting --> Completed | N=120 --> 53

Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

To determine the test's utility in identifying which patients with EBC in the IDEAL (Investigation on the Duration of Extended Adjuvant Letrozole) trial could benefit from 5-year vs 2.5-year letrozole treatment...These findings suggest that this gene expression assay could go beyond guiding neoadjuvant and adjuvant chemotherapy decisions to informing the optimal duration of adjuvant endocrine therapy. EU Clinical Trials Register Eudra CT: 2006-003958-16.

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.

Promising derivatives revealing low damage to healthy cells were subject to enzymatic inhibitory assessment against ARO and EGFR and their activities compared to letrozole and erlotinib respectively...Eventually, molecular docking analysis revealed that hit compounds 3c, 4c, 4d, and 6a could bind favorably to the proposed in silico models of various protein-ligand interactions. Therefore, our promising top candidates, by demonstrating appreciable anti-breast cancer activities, present valuable prospects for optimization, potency enhancement and future application.

Introduction The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. Conclusion The INGE-B trial demonstrated good efficacy and tolerability of PAL with letrozole (1L) or fulvestrant (first and later line) in accordance with the PALOMA-trials. In addition, the so far lacking proof of efficacy and safety of PAL in combination with anastrozole or exemestane in 1L and with letrozole in later line was provided by INGE-B.

Spatial analysis reveals frequent gene expression and copy number heterogeneity in ER+ HER2- BC. Work aiming to quantify gene expression differences between subclones is ongoing.

57.14% (4/7) received adjuvant Letrozole for a minimum of 5 years. The patient with a recurrence score of 24 received adjuvant chemotherapy and developed metastatic 4 years post diagnosis while on Tamoxifen...Genomic tests have resulted in a significant reduction in the number of patients receiving adjuvant chemotherapy. However, a more multifacted approach may be required to tailor treatment decisions incorporating genomic testing, clinicopathological features and individual characteristics with the aim of improving outcomes for patients with hormone receptor positive early breast cancer.

Eligible pts (n=81) will undergo baseline (BL) breast MRI and tumor/blood collection, followed by a 28-day cycle of anastrozole (ana) (+/- 14 days, C1), during which BC risk category will be determined based on BL tumor Ki67 and study-funded Prosigna(R) PAM50 subtype...If responses are observed in ≥16 pts among 23 ORR evaluable pts, the trial claims preliminary efficacy. The study is actively enrolling pts at Siteman Cancer Center.

This is a retrospective study of paired samples from patients (pts) with hormone receptor-positive and HER2-negative (HR+/HER2-) EBC treated at Hospital Clinic of Barcelona between 2014 and 2023 and from the letrozole arm of SOLTI-1501 VENTANA trial (Adamo et al...All pts received POET for 2 to 12 weeks prior to surgery, with tamoxifen or aromatase inhibitors (AI), administered according to menopausal status... POET is a simple and secure treatment that can be administrated before surgery in HR+/HER2- EBC. The molecular profiling and dynamic evaluation of biological changes induced by POET could offer opportunities for a better understanding of the tumor´s sensitivity to endocrine therapy and could help guide and optimize treatment strategies in HR+/HER2- EBC.

P2, N=20, Completed, Helsinki University Central Hospital

P2, N=137, Recruiting, Dartmouth-Hitchcock Medical Center | Trial completion date: Sep 2024 --> Aug 2029 | Trial primary completion date: Sep 2024 --> Feb 2026

In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2- mBC and CVD.

P1, N=31, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jul 2024

In addition, the proportion of developing granulomas decreased and that of mature granulomas increased in the liver, while there was no significant change in organ architecture in the spleen. Based on these data, repositioning of LET may be promising for the treatment of visceral leishmaniasis in humans.

In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content...Pharmacological inhibition of complex I suppressed the tumor-forming potential of persisters and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts...Endocrine-tolerant persister cancer cells that survive endocrine therapy can cause recurrent disease. Persister cells exhibit increased energetic dependence upon mitochondria for survival and tumor re-growth potential.

Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.

P2; Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009.

This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination.

On rare occasions, PBL can preoperatively mimic TNBC. While this case did not lead to serious consequences, because surgery was eventually selected as the first therapy, clinicians should be aware that the diagnosis of PBL is challenging using only a core-needle biopsy and can often be misdiagnosed as TNBC.

The patient was treated with letrozole and adjuvant radiotherapy...Although glucocorticoid treatment has also been widely used for NICTH, few reports have demonstrated efficacy for NICTH secondary to phyllodes tumor. We report a rare case of malignant phyllodes tumor of the breast resulting in NICTH and demonstrated good response to glucocorticoids as a bridge to definitive surgery.

In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.

The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.

In vivo, the probe effectively targeted neoangiogenesis and Pancreatic Intraepithelial Neoplasias (PanINs) in various PDAC models, including the orthotopic, ectopic, spontaneous, and tamoxifen-induced tumors. Furthermore, multiple LTZi-MHI148 administrations attenuated PanINs to PDAC progression, suggesting its potential as a therapeutic intervention. These findings underscore the translational potential of LTZi-MHI148 for the early detection and targeted therapy of PDAC, utilizing NIR-I/II imaging to monitor RhoJ overexpression in precancerous ductal neoplasia associated with neoangiogenesis.

From molecular docking and analysis of interactions with the amino acid residues of the binding cavity, it was found that the amino acid residues interacting with the non-steroidal inhibitors exhibited π-stacking interactions with PHE134, PHE 221, and TRP 224, while the steroidal drug exemestane lacked π-stacking interactions...Additionally, anthraquinone compounds with minor structural modification can also serve to be potential aromatase inhibitors. The in silico protocol utilised can be useful in the drug discovery process for development of new leads from structurally diverse set of natural products that are comparable to the drugs used clinically in breast cancer therapy.

P=N/A, N=168, Recruiting, University of Oklahoma | Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Jun 2025

P2, N=65, Active, not recruiting, University of California, San Francisco | Trial completion date: Jul 2024 --> Jan 2025

P2, N=74, Completed, GOG Foundation | Active, not recruiting --> Completed

These findings, supported by molecular docking scores and MM-PBSA binding energies, advocate for their potential superior inhibitory capability against the AKT1 enzyme. Nevertheless, it is crucial to validate these computational predictions through in vitro and in vivo studies to thoroughly evaluate the therapeutic potential and viability of these compounds for AKT1-targeted breast cancer treatment.

There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC.

No abstract available

P2, N=30, Recruiting, University of Pennsylvania | Not yet recruiting --> Recruiting

P2, N=201, Completed, Priscilla McAuliffe | Active, not recruiting --> Completed

In vivo, we chemically induced breast cancer using DMBA (50 mg/kg BW) in Wistar rats, then treated them with oligandrin (1 mg/kg BW) or standards (tamoxifen 3.3 mg/kg; letrozole 1 mg/kg) for 20 weeks. Oligandrin prevented high-grade adenocarcinomas according to SBR stratification and significantly reduced pro-inflammatory cytokine levels (IL-6, IL-12) while increasing anti-inflammatory cytokine levels (INF-γ). Oligandrin is reported for the first time to protect against breast cancer onset and this effect seems to be at least in part attributable to its immune-boosting capacity.

These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.

In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in non-malignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy.

P=N/A, N=90, Recruiting, University of Maryland, Baltimore | Trial primary completion date: Mar 2024 --> Jul 2024

P3 | N=3966 | "Agendia, Inc. today announced that the NSABP B-42 study evaluating the MammaPrint assay in predicting the benefit of extended endocrine therapy (EET) in early-stage breast cancer patients was published in the July issue of Journal of Clinical Oncology.... The data revealed that only MammaPrint Low (non-UltraLow) Risk tumors showed a statistically significant 10-year EET benefit of 9.5% for disease-free survival (DFS) and 7.9% for breast cancer-free interval (BCFI). Conversely, MammaPrint UltraLow and High Risk tumors did not derive statistically significant EET benefit."