HR positive + HER-2 negative

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.

No abstract available

Furthermore, the side effects were manageable and no dose reductions were necessary during treatment. These findings suggest that the combination of CDK4/6i and ET in the treatment of HR+/HER2-advanced breast cancer cannot be underestimated.

In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).

Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

P2, N=44, Recruiting, Marina N Sharifi | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

IHC3 is able to define prognostic groups in patients with node-negative, HRpos/HER2neg eBC. Node-negative patients with a high IHC3 score had the worst prognosis, which was comparable to that of node-positive patients described in recent trials. This simple and cost-effective tool could thus potentially aid in identifying patient groups for innovative therapeutic approaches.

The binding energy range for these ligands against their respective targets was calculated to be between -15 and -5 kcal/mol. Finally, based on general and common rules in medicinal chemistry, we selected 2, 3, 3, and 8 new ligands with high priority for further studies in the EGFR+HER2, ER, NF-κB, and PR classes, respectively.

CDK4/6 inhibitors with endocrine therapy are effective in elderly patients with metastatic HR+/HER2- breast cancer, though careful management is crucial to balance efficacy and minimize adverse events.

This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

Additionally, in a real-world scenario, it is more likely that CAB will be performed on CNB first. Conclusion CAB when performed on CNB samples showed high concordance with SS thus demonstrating that CNB was a suitable sample for the CanAssist Breast test. The accuracy in the low-risk category is 97.5%, which ensures that physicians can reliably use prognostic information by testing CNB to guide adjuvant therapy decisions.

When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at lower dose in clinical practice, though without evidence. The aim of the IMPORTANT-trial, a pragmatic, multinational, open-label, partly decentralized randomized trial is to investigate whether lower starting dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older (≥70 years old) patients with advanced HR+/HER2- breast cancer who are assessed as vulnerable or frail based on comprehensive geriatric assessment.Clinical Trial Registration: NCT06044623 (ClinicalTrials.gov); Registration date: 13 September 2023.

P1/2, N=138, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

In this real-world database, disparities in receiving 1st -line CDK4/6 inhibitors were seen by age, diagnosis stage, baseline performance status, comorbidity, and insurance status. In adjusted analysis, the use of 1st -line CDK4/6i plus ET yielded better PFS and OS rates than ET alone. Further efforts are essential to enhance equitable use of and access to this crucial drug class.

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.

Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.

In our analysis, HER2 status did not have a significant impact on treatment response to CDK4/6i.

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 efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.

Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

P=N/A, N=419, Recruiting, Ipsen | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

P4, N=130, Completed, German Breast Group | Recruiting --> Completed | Trial completion date: Mar 2023 --> Aug 2024 | Trial primary completion date: Mar 2023 --> Aug 2024

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

In the HR-positive/HER2-negative group, PFS for endocrine therapy was significantly longer than chemotherapy, with no differences in OS. This study confirms that endocrine therapy is preferred as an FLx for ABC in the HR-positive/HER2-negative group.

P3, N=312, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

P2, N=37, Completed, Fudan University | Recruiting --> Completed

P1, N=80, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

The presence of liver and bone metastases was associated with worse prognosis and survival; additionally, patients with worse performance status had shorter overall survival. These findings underscore the need for personalized therapies, opening new lines of future research.

With the evolving landscape of neoadjuvant therapies in development for HR-positive/HER2-negative breast cancer, ongoing work using quantitative biomarkers and genomic assay scores is needed to select the right neoadjuvant systemic therapy for the right patient. Given the increasing amount of data available at the time of breast cancer diagnosis, novel computational approaches are needed to integrate patient demographic and tumor-specific factors to predict the optimal treatment strategy and likelihood of BCS.

Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.

P1, N=32, Active, not recruiting, Adrienne G. Waks | N=50 --> 32

Many women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

P1/2, N=192, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Aug 2026 | Trial primary completion date: Dec 2026 --> Aug 2026

These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

According to our results, the Prosigna assay was found to be a relevant tool for the clinical decision making process. Long-term follow-up of these patients will elucidate the potential benefits of using multigene molecular tests as biomarkers for treatment.

This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS.

The analysis revealed that the six most effective neoadjuvant treatment regimens for HR+/HER2- breast cancer were: CT(A)+olaparib (82.5%), CT(A)+nivolumab (76.5%), Com (74.9%), CT (72.1%), Mono+eribulin (72.0%), and CT(A)+pembrolizumab (70.4%).Paired meta-analysis for pathological complete response (pCR) found no statistically significant distinction between treatment regimens that included both anthracycline and immunosuppressants and regimens that relied solely on anthracycline chemotherapy(OR:1.14, 95%ci 0.79-1.64, I2 = 71%, P=0.50). Although pCR is valuable in assessing the effect of neoadjuvant therapy in some cases, prognostic prediction and efficacy assessment in patients with HR+/HER2- breast cancer should be based on a combination of broader clinical and biological characteristics. PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024534539, CRD42024501740.