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."

Many of the genes that we identified warrant further research to elucidate the more specific molecular mechanisms of Letrozole resistance in this patient population and could potentially be used as prognostic markers with further wet lab validation. We anticipate that these findings could contribute to improved detection and therapeutic outcomes in aromatase-resistant ER+ breast cancer patients.

The primary hypothesis of predictive ability of MP on DR was not confirmed. However, the secondary outcomes demonstrated MP was predictive of ELT response and identified a subset of patients with early-stage hormone receptor-positive BC (MP-LR) with improved outcomes from ELT. These data could have important clinical implications in patient selection beyond clinical risk assessment for EET.

Herein, we present the first case ever reported, concerning a female patient with de novo metastatic breast NEC who received hormonal therapy, a combination of a CDK4/6 inhibitor palbociclib with letrozole and triptorelin, as first-line treatment with significant clinical and radiological response. As most NECs are estrogen receptor and/or progesterone receptor positive and HER-2 negative, we suggest that hormonal therapy may play a leading role even in the first-line setting. The present report provides a new treatment strategy by incorporating CDK4/6 inhibitors in the therapeutic armamentarium of breast NECs.

It has been detailed how different reported AIs were designed, their SAR investigations, in silico analysis, and biological evaluations. Various AIs from multiple origins, such as synthetic and semi-synthetic, have also been discussed.

P2, N=21, Completed, Mayo Clinic | Recruiting --> Completed | N=50 --> 21 | Trial completion date: Jun 2025 --> Sep 2023 | Trial primary completion date: Jun 2024 --> Sep 2023

Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

After surgery, she underwent irradiation of the remaining breast (50Gy) and took tamoxifen orally for 10 years...After surgery, the patient was scheduled to receive four courses of TC therapy followed by oral anastrozole for 10 years...However, there is debate about performing 2nd SNB and additional treatment when metastasis is found. In this study, we performed 2nd SNB using the RI method + dye method, and experienced a case in which an SN was identified in the contralateral axilla, and we will discuss this case based on a literature review

Two cases refused chemotherapy, but all cases received endocrine therapy (tamoxifen in 13 cases, anastrozole in 10 cases, and letrozole in 2 cases). The median age was 52 (36-75) years, 11 patients (44%) were aged 50 years or younger, 14 patients (56%) were over 50 years old, 13 patients (52%) were premenopausal, and 12 patients (48%) were postmenopausal. Five patients (20%) had pT3 or greater infiltration size, five patients (20%) had nuclear grade 2 or greater, three patients (12%) had lymphatic invasion, 14 patients (56%) had high Ki-67 (>20), and 18 patients (72%) had positive lymph nodes. RS was low in 4 cases (36%), mid in 5 cases (46%), and high in 2 cases (18%), LR in 12 cases (86%), and HR in 2 cases (14%), all of which were aged 50 years or less.

The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.

Our findings highlight Quercetin 3-gentiobioside as a standout candidate, demonstrating superior binding affinity (-10 kcal/mol) and an estimated Ki of 46.77 nM compared to letrozole and other okra compounds. Molecular dynamic analysis confirms the stability of Quercetin 3-gentiobioside binding in terms of H-bonds and conformational integrity. In conclusion, our computational investigation identifies Quercetin 3-gentiobioside, along with Quercetin 3-O-rutinoside and Hyperin, as promising candidates for preclinical studies in the pursuit of potential Aromatase inhibitors.Communicated by Ramaswamy H. Sarma.

Further investigations led to bilateral invasive lobular breast carcinoma diagnosis. Epirubicin cycophosphamide was prescribed after progression under letrozole ribocilib therapy.This case aims to raise awareness among clinicians about the importance of ruling out breast cancer in patients with peritoneal carcinosis and paying attention to digestive symptoms in breast cancer patients with careful gastric endoscopic examination to avoid misdiagnosis.

Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.