HR positive + HER-2 negative

This case highlights the need for awareness of acute, severe hyperglycemia as a potential adverse effect of capivasertib and similar oncologic agents. Clinicians should ensure at least twice weekly blood glucose monitoring for any degree of capivasertib-induced hyperglycemia, and have high suspicion for this contributing factor in cases of severe hyperglycemia.

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

In hormone receptor-positive, HER2-negative breast cancers, a growing number of revolutionized personalized therapies are in clinical use or on trials, such as CDK4/6 inhibitors and immune checkpoint inhibitors in adjuvant and neoadjuvant settings, and PIK3CA inhibitors in metastatic disease. In this review, we focus on biomarkers associated with those new therapeutic targets and molecular applications for genetic alterations associated with drug resistance or interaction from a pathology perspective for selecting and optimizing breast cancer treatment.

CT-defined low SMD predicts poor treatment outcomes in patients with ABC undergoing first-line treatment with aromatase inhibitors and CDK4/6i.

By analyzing clinical evidence, commercial presence, reimbursement mechanisms, guideline recommendations, regulatory pathways, and local experiences, this study reveals the complex factors that influence the adoption of personalized medicine technologies. By highlighting these challenges, this article offers valuable insights into strategies to facilitate the integration of innovative diagnostic tools into clinical practice across Europe, ultimately leading to improved treatment decision-making for cancer patients.

This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.

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.

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.

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

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.

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.

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.

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

P2, N=40, Recruiting, Rutgers, The State University of New Jersey | Not yet recruiting --> Recruiting

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

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.

Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information.

Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.

Both tumor subtypes displayed varied IC compositions based on PD-L1 status. In conclusion, IC composition and spatial distribution in high-TIL TNBC and HR + HER2-BC significantly differ, influenced by PD-L1 status.

This retrospective study included 193 patients who received either ribociclib or palbociclib in combination with first-line ET. Multivariate analysis identified the symptomatic disease and liver metastasis as independent predictors of shorter mPFS (HR; 1.835, 95% CI; 1.146-2.939 and HR; 2.433, 95% CI; 1.329-4.454, respectively). Our analysis revealed that although symptomatic individuals who underwent CDK4/6 inhibitor plus ET experienced a significant reduction in mPFS durations compared to asymptomatic patients, the 22-month mPFS indicated that CDK4/6 inhibitor plus ET is an effective treatment option.

CCND1 amplification is a recurring event in breast cancer, occurring most frequently in luminal B-like and HER2-amplified subtypes. A trend toward less favorable outcomes was observed among CCND1-amplified HR-positive, HER2-negative tumors.

Concomitant use of PPIs with ribociclib or palbociclib did not affect the efficacy of either CDK4/6 inhibitor. PPIs can be administered alongside these medications when clinically indicated.

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).

Trophoblast cell-surface antigen 2 (TROP2), a transmembrane receptor expressed in many carcinomas, is a target for novel antibody-drug conjugates such as sacituzumab govitecan...In metastases, the interobserver variability was similar for both methods. Our observations support the application of the HER2 ASCO/CAP guidelines for semi-quantitative evaluation of membranous TROP2 protein expression, as this method strongly correlates with the H-score and is less prone to interobserver variability in post-NAC breast resections. Future studies should investigate the association between the TROP2 membrane score and response to TROP2-targeted therapy.

Greater familiarity of healthcare professionals with the overall clinical and pathological findings in PHTS and the validated Cleveland Clinic PTEN calculator (http://www.lerner.ccf.org/gmi/ccscore) would improve the recognition of female PHTS individuals with breast cancer. Earlier identification of their cancer predisposition syndrome would benefit these patients and their families who are at high risk of a range of cancers.

In conclusion, HR+/MP-H2 cancers closely resemble TN breast cancers in transcriptional and clinical features and benefit from similar treatment strategies.

Several Trop-2-targeted ADCs, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-DXd), have demonstrated significant antitumor activity in clinical trials for both triple-negative breast cancer (TNBC) and hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Notably, Trop-2-targeted ADCs have shown promise in reprogramming the tumor microenvironment through multiple signaling pathways, potentially enhancing antitumor immunity. This review aims to provide new insights and research directions for the development of innovative breast cancer therapies, offering potential solutions to improve treatment outcomes and quality of life for breast cancer patients.

Outcomes analyses in this high-risk, HER2-negative eBC population suggest a continued unmet clinical need.

Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.

Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

Dose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.

This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings.

NOLUS positivity was observed in 20.43% of patients aged 22-50, compared to 8.93% in those over 50, though this difference was not statistically significant. NOLUS exhibits potential in predicting pCR in HR+/HER2- breast cancer, serving as a cost-effective substitute for genomic tests.

P=N/A, N=200, Not yet recruiting, AstraZeneca

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Pts with HR+ HER2- aBC from a phase II trial of an alternative schedule of palbociclib (palbo alt dosing trial NCT 3007979) and from a retrospective CDK4/6i study were included in this analysis...The majority of these pts received palbo (10/10) paired with letrozole (8/10) and did not have recurrence on adjuvant endocrine therapy (8/10)... Early progression on CDK4/6i is associated with a particularly poor prognosis; however, there are patients with exceptional response to CDK4/6i who may remain on therapy for an extended time. There were variations in the mutation profiles between the two cohorts, though this data set was limited in size. Additional analysis of genomic variants is needed to identify profiles of patients who may significantly benefit from CDK4/6i.

Before Oncotype DX results, clinician recommended CT for 60.1% of pts, with docetaxel-cyclophosphamide (59.1%) as the preferred chemotherapy regimen. Without Oncotype DX results, the agreement in treatment recommendations between GTP-4o and clinicians was modest, and this discordancy deserve deeper investigation. Pre-test indications provided by GPT-4o were less impacted by the multigene assay results, maybe due to the capability of AI to better approximate Oncotype DX results. After Oncotype DX results, the agreement between AI and clinicians was extremely high indicating the key role of multigene testing in guiding treatment decisions.

Conclusions Our highly integrated infrastructure allows us to collect and integrate unprecedented longitudinal multiomic molecular data from HR+/HER2- mBC patients. A combination of genomic, transcriptomic, and epigenetic analyses will provide a more accurate characterization of primary and acquired resistance mechanisms to CDK4/6i.