ER positive + HER-2 negative

A total of 94% of patients >74 years with T1a/b, ER positive HER2 negative breast cancer were node negative. Nodal status significantly influences adjuvant treatment in this patient group and therefore, we recommend clinicians consider tumour factors and patient fitness in their decision making about SLN biopsy in the elderly population with hormone receptor positive early breast cancer.

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).

In this study, we present the largest cohort published to date of breast cancer patients who received CDK4/6i alongside bone-directed RT. Although the observed differences in survival were not statistically significant, RT remains a viable treatment modality in metastatic breast cancer in some patients.

This study confirms first-line CDK 4/6i effectiveness, with abemaciclib and ribociclib showing prolonged PFS vs. palbociclib. This study could not confirm a ranking of the three CDK 4/6i.

The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.

Implementing the Oncotype DX test for women with ER-positive and HER2-negative early breast cancer is of great value. Delayed implementation leads to increased costs, reduced quality of life, and life-years lost.

In this retrospective analysis, there were differences in treatment assignments based on clinical risk of PMBC that were consistent with treatment recommendations according to RS outcomes in EBC. The binary RS result cut offs (RS ≤25; RS >25) were prognostic for PFS and OS in this retrospective analysis of patients with ER+/HER2- PMBC. These findings suggest that the Oncotype DX® assay also reflects tumor biology in PMBC, and genomic assays standardly used in early breast cancer might warrant further prospective investigation in the treatment-naïve advanced setting.

95GC can predict recurrence risk in patients with ER+, HER2-, N1 breast cancer. It also suggested that it may be able to predict the risk of recurrence better than RS of 21-gene signature assay.

PFS (p=0.003) and OS (p=0.03) differed significantly by logrank test between the four groups: Low-Low-Low (n=14) median PFS and OS not reached; High-Low-Low (n=26) PFS 23.8m (95%CI can't be calculated) and OS 51.8m (95%CI 15.4 to 88.1); High-Low-High (n=24) PFS 17.5m (95%CI 10.2 to 24.8) and OS 34.3m (95%CI15.1 to 53,7) High-High-High PFS 10.3m (95%CI 1.73 to 18.9) and OS 30.3m (95%CI 15.1 to 45.6) In exploratory analyses no significant differences between median TKa at C1D15 or C2D1, or early TKa dynamic patterns were observed between patients treated with palbociclib (n=48) vs ribociclib (n=29), p=0.33 to 1.0. TKa analysis at later time points is ongoing. TKa is an encouraging biomarker for personalized disease monitoring in MBC.

274 of 1134 pts (24.2%) had de novo mBC in the overall cohort, 33 of whom self-identified as Black (12.0%) and 210 as White (76.6%). 26.2% of pts had ctDNA collection prior to any therapy, 24.0% after 1st line therapy, and the remaining pts after 2 or more lines of therapy. In the ER+/HER2- population, there were 193 pts (193/855, 22.6%) with de novo mBC, of whom 29 were Black (15.0%).

The findings from this window-of-opportunity study highlight the need for larger cohort analyses to validate these initial observations and further investigate the clinical impact of these racial differences in breast cancer biology and treatment response.

Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer.

P1, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87-0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78-0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population.

ER-positive/HER2-negative BC in AYA was highly proliferative with high immune cell infiltration compared with the other age groups.

In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

Between 2011 and 2022, assay use resulted in a 58% reduction in chemotherapy administration and net savings of over €3.3 million.

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.

P3, N=287, Active, not recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2025

The combination of TILs and MRI is informative of response to NAC in patients with both ER+/HER2- and TN&HER2+ tumors.

In cN0, postmenopausal ER-positive/HER2-negative patients who underwent BCT, patients with cT1 tumors had lower rate of LN metastasis, and there were fewer instances of HNB. Therefore, in these patients, omission of axillary surgery including SLNB can be carefully considered.

NLR at EOT with CDK4/6 inhibitors is a significant and independent prognostic marker for patients with ER-positive HER2-negative advanced breast cancer.

No such effect was observed for ESR1 mutations, with a rate ratio of 1.15 (confidence interval 0.67-1.95). We conclude that ER loss and ESR1 mutation together account for 30% of the resistance to endocrine therapy.

We present the largest study of BC variant frequencies in a cohort of Irish breast cancer patients to date and confirm NGS is feasible and identifies clinically relevant and actionable variants. We confirm that the frequency of PIK3CA alterations, in addition to codon specificity, are comparable to those observed in European and US cohorts and demonstrate that the detection of clinically relevant biomarkers is not confined to ER positive HER2 negative BC. The tissue failure rate (19%) underscores the need for cfDNA testing to identify the expanding range of actionable targets in BC to improve access to emerging targeted therapies and biomarker-driven clinical trials.

P1/2, N=66, Active, not recruiting, Stephen Shiao | Trial primary completion date: Mar 2022 --> Dec 2024

The DESTINY-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) significantly prolonged the survival of patients with HER2-low breast cancer, thus presenting a paradigm shift in anti-HER2 therapy...We inferred that the HER2-low and HER2-zero statuses do not affect the RFS and OS of patients with ER-positive breast cancer. The prognostic significance of HER2-low or HER2-zero status in luminal A- and B-like breast cancers might differ, and a new treatment strategy is required for the HER2-low subgroup.

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2024 --> Mar 2025

P=N/A, N=221, Not yet recruiting, Università Vita-Salute San Raffaele | Phase classification: P2 --> P=N/A | Initiation date: Oct 2023 --> Oct 2024

In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

Clinicopathologic features including patient age, race, clinical T category, grade, Ki67, ER/PR expression, and tumor location are associated with nodal positivity in women 50-69 years of age with cT1N0, ER+HER2- breast cancer. The 21-gene RS is not associated with nodal positivity. This predictive model is able to identify women at high risk for nodal metastasis and may help multidisciplinary teams as they look to consider de-escalating SLN surgery in breast cancer.

The nomogram, integrating CESM deep learning with clinical-pathological features, proved valuable for predicting NAC response in patients with ER-positive/HER2-negative breast cancer. Nomogram outperformed deep learning-based and clinical models.

P1/2, N=15, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2025 --> Apr 2024

The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.

The results from this clinical evaluation of image-based risk stratification shows a considerable agreement to an established gene expression assay in routine breast pathology.

P=N/A, N=24, Recruiting, BioCorteX Inc | N=60 --> 24

Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.

Predictive biomarkers of response to neo-adjuvant chemotherapy and hormonal therapies are instrumental for selecting ER positive/HER2 negative breast cancer patients for each treatment. Chemotherapy remains the standard of care for many of those patients requiring neo-adjuvant treatment, but other neo-adjuvant therapies are increasingly used.

While there now exist well-validated geriatric assessment tools whose use is encouraged by the American Society of Clinical Oncology when considering systemic therapy, these instruments have not been widely integrated into the locoregional breast cancer care model. This review aims to highlight the importance of assessing frailty and the concepts of and over- and undertreatment, in the context of trial data supporting opportunities for safe deescalation of locoregional therapy, when treating older women with early-stage breast cancer.

Abemaciclib was originally FDA approved for patients with ER-positive/HER2-negative breast cancer with Ki-67 expression ≥20%...The average Ki-67 difference was 4.36 for CNB vs RES, 6.95 for CNB versus ALN, and RES versus ALN (P=0.93, 0.99, and 0.94, respectively). Our study concludes that further refinement in Ki-67 scoring is advisable to reduce clinically significant variation.

P2, N=81, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> Feb 2025

P=N/A, N=60, Recruiting, BioCorteX Inc | Not yet recruiting --> Recruiting