HR positive

We observed significant positive patient-level correlations between DFS and OS, IDFS and OS, and DDFS and OS in early-stage HER2- BC. Our IDFS and DDFS findings advance the understanding of the role of these DFS endpoints as predictors of OS, and their potential utility as surrogate endpoints in clinical trials of early-stage HER2- BC, given additional validation in trial-level meta-analyses.

The PFS benefit was more pronounced in those individuals who received abemaciclib or ribociclib as second CDK4/6i. Continuation of CDK4/6 inhibition was associated with higher rates of grade 3 and 4 neutropenia (range: 25-40%) and anemia (range: 1.7-11%). In conclusion, switching CDK4/6i and ET conferred a statistically significant improvement of PFS in comparison to ET alone in patients with progression or recurrence on prior CDK4/6i-containing therapy.

We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/ Protein Kinase B (AKT)/ mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

P3; NHB women had worse clinical outcomes compared to NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors.

This research is corroborated by an in-house cohort showing lower survival rates in TNBC patients with higher cholesterol production gene activity. This suggests a new treatment approach for TNBC by simultaneously targeting CDK4/6 and CDK7, warranting additional clinical trials.

Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2-, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting...Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.

8 vs. 141.1 months; HR: 1.95; 95% CI: 1.28-2.98; p = 0.002) and OS (median, 169 vs. 261.1 months; HR: 2.56; 95% CI: 1.6-4.12; p < 0.001) in stage 2 and shorter OS (median, 65 vs. 183.1 months; HR: 3.25; 95% CI: 1.19-8.83; p = 0.021) in stage 3. Elevated postoperative CEA indicates worse DFS and OS in patients with HR-positive/HER2-negative early breast cancer.

We report a case of a 61-year-old female with HR+HER2- metastatic breast cancer (MBC) who developed resistance to fulvestrant and subsequent chemotherapy but achieved a durable partial response (PR) lasting more than 22.5 months following ESG401 treatment. Furthermore, the patient's exceptionally long clinical benefit distinguishes her from other patients receiving ESG401 treatment. Further exploration of the use of ESG401 in HR+HER2- MBC patients, as well as a deeper understanding of the characteristics of patients that may impact sustained efficacy, in expanded clinical trials is warranted.

Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.

Patients with oligoprogressive mBC, especially with HR+/HER2- disease and non-visceral OPD after a durable pre-OPD PFS, benefit from OPD-directed SBRT while maintaining the same systemic treatment, suggesting its broader implementation in clinical practice.

Dosing schedules other than the standard 3/1 schedule can be used to continue palbociclib with HR+/HER2-MBC while ensuring therapeutic efficacy. Alternative dosing schedules look promising and need further research (preferably, prospective studies) with a larger sample size and longer follow-up to validate treatment efficacy.

P=N/A, N=30, Recruiting, Emory University | Trial completion date: May 2025 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Feb 2026

P2, N=20, Active, not recruiting, Yuan Yuan | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2026 --> Oct 2024

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.

Interestingly, full-time employment was associated with improved breast cancer DFS. These findings highlight the importance of considering genetic ancestry beyond self-reported race and accounting for social determinants of health, in efforts to improve survival outcomes among Black women with breast cancer.

This study elucidates the immunosuppressive role of ER signaling in breast cancer, highlighting a complex interplay between cancer, stromal, and immune cells and reveals potential approaches to enhance immunogenicity in HR+ breast cancer. These findings offer crucial insights into immune evasion in breast cancer and identify strategies to enhance T cell abundance.

Patients with HR+/HER2-negative BC and TNBC recurrence incurred higher monthly all-cause (cost difference &lsqb;CD]: $3,988 and $4,651) and BC-related healthcare costs (CD: $3,743 and $5,819). Our findings highlight the considerable economic burden of recurrence in early-stage HER2-negative BC and underscore the unmet need for optimization of therapies that reduce recurrence in this population.

Pseudo-Scr elevation appears to be a class effect of CDK4/6i, with similar rates of Scr elevation observed across the three agents currently FDA approved.

P=N/A, N=15, Active, not recruiting, HealthPartners Institute | Recruiting --> Active, not recruiting

Research on the potential role of immunotherapy, particularly programmed cell death protein 1/programmed cell death ligand 1 inhibitors, is rapidly expanding in both the early and metastatic settings with some preliminary evidence suggesting benefit when used as part of combination therapy. Several ongoing phase 3 studies should help define their future role in treating these patients.

The study revealed proteomic signatures of patients with luminal A breast cancer, identified multiple differential proteins, and identified three plasma proteins as potential diagnostic biomarkers for breast cancer. It provides a reference for the screening of biomarkers for breast cancer.

BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.

Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly...In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. ClinicalTrials.gov Identifier: NCT05325632.

It is used for the treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with at least one alteration on PIK3CA/AKT1/PTEN. In this short perspective, Capivasertib's physicochemical properties, synthesis, mechanism of action, binding mode, pharmacokinetics, drug interaction studies, and treatment-emergent adverse events are discussed.

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.

P=N/A, N=41, Completed, University of Saskatchewan | Active, not recruiting --> Completed

At its current price, our analysis suggests that the addition of capivasertib to fulvestrant as a second line treatment is not cost effective versus fulvestrant alone at a willingness-to-pay threshold of $100,000/QALY. The price of capivasertib will need to be reduced by nearly 70% (to $7000 per cycle) for it to become cost effective.

P1, N=100, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2024 --> Apr 2025

P=N/A, N=104, Active, not recruiting, University of Arkansas | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P1, N=890, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Recruiting --> Active, not recruiting

FDG PET/CT SUV-LN effectively predicts ALN metastasis in HER2-positive and TNBC subtypes. Hormone receptor-positive breast cancers show lower FDG uptake in metastatic ALNs, reducing diagnostic accuracy. This finding may aid in selecting the most appropriate diagnostic modality based on tumor characteristics in the era of personalized medicine.

However, the incidence of early-stage breast cancer (stages 0 and I) continued to increase, accounting for 65.6% of newly diagnosed cases in 2021. Our results showed that the overall survival rate for patients with breast cancer has improved, primarily due to a rise in early-stage diagnoses and advancements in treatment.

RSClinN+ provides improved estimates of prognosis and absolute CET benefit for individual patients compared with RS or with clinical data alone and could be used in patient counseling.

P=N/A, N=32, Active, not recruiting, Spanish Breast Cancer Research Group | Trial completion date: Jul 2024 --> Jan 2026 | Trial primary completion date: Jul 2024 --> Sep 2025

P=N/A, N=16, Recruiting, Rutgers, The State University of New Jersey | Not yet recruiting --> Recruiting

While some benefit, albeit modest, has been observed from switching to a different CDK4/6i after progression (e.g. ribociclib after palbociclib in the MAINTAIN trial and abemaciclib after both palbociclib and ribociclib in the postMONARCH trial), the current evidence (mainly with palbociclib) clearly argues against maintaining the same CDK4/6i. However, selected patients with indolent disease, prolonged exposure to previous CDK4/6i treatment (especially palbociclib) and without actionable molecular alterations, may be suitable for suchmaintenance strategy beyond progression. In this challenging and rapidly evolving treatment landscape, ongoing studies can refine the optimal approach and identify clinical and molecular factors to select the best treatment for the right patient.

This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.

Multivariate logistic analysis showed that the CRP level was a significant independent predictor of pCR (OR = 5.882, 95% CI: 1.470-28.57, P = .017). High CRP levels were found to be associated with a higher pCR rate, indicating their independent predictive value in determining the efficacy of neoadjuvant chemotherapy in hormone receptor-positive BC patients.

Currently, there are three ADCs available for use in breast cancer: trastuzumab emtansine for HER2 positive breast cancer (early stage and metastatic), trastuzumab deruxtecan for HER2 positive and HER2 low breast cancer (metastatic) and sacituzumab govitecan for triple negative and hormone receptor positive (HR +), HER2 negative breast cancer(metastatic). The future of this class of compounds is very exciting. This field is rapidly evolving with new ADCs being investigated and clinical trials looking at the use of known ADCs in earlier stage disease.

Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.

Discrepancy in the HER2 status of the metastases and of CTCs was observed in approximately one third of patients. Measuring HER2 on CTCs could potentially offer a means to longitudinally monitor HER2 status during therapy and simultaneously address challenges such as tumor heterogeneity. Therefore, the predictive value of HER2 on CTCs should be further investigated in clinical trials.

NACT was more effective in the molecular and dimensional tumor 'downstaging' than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.