HER-2 negative + ER positive

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

Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028

Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).

SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynaecologic carcinoma, a potential diagnostic pitfall. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations, without specific genetic underpinnings identified. Additional studies are warranted to further evaluate the clinical behaviour of these tumours.

Therefore, we suggest that there is an underappreciated association between the HER2-low subtype and endocrine resistance. In this perspective piece, we explore the evidence linking the HER2-low subtype with the various pathways to endocrine resistance and suggest that there are signaling networks in HER2-low tumors that intersect endocrine resistance and can be effectively targeted.

Given low rates of genomic testing uptake nationally, image-based methods may help identify ER+/HER2-patients who could benefit from testing.

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.

These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.

P2, N=65, Active, not recruiting, Jules Bordet Institute | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2024 --> Jan 2025

P2, N=333, Completed, Queen Mary University of London | Unknown status --> Completed

P1, N=214, Active, not recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting

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.

Based on real-world data analysis, in ER-positive, HER2-negative post-menopausal women with early breast cancer in Taiwan, the use of tamoxifen compared to AIs is associated with a lower risk of recurrence. Improved adherence to medication can break the cycle of recurrence and improve health outcomes.

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).

Computational biomarkers, representing spatial properties of the tumor proliferation and immune cell infiltrates, provided independent prognostic information beyond conventional IHC markers in BC. Integrating Ki67-entropy and CD8-immunogradient indicators into prognostic models can improve patient stratification with regard to BCSS.

We judged that both patients were at intermediate risk of recurrence and administered S-1 in addition to endocrine therapy. Even in cases without axillary lymph node metastasis, this combination of S-1 with endocrine therapy was considered to be a useful treatment option if the criteria of the POTENT trial were met.

Surgery was not possible due to comorbidities, so fulvestrant(500 mg/month)+denosumab(120 mg/month)was started. Furthermore, as the tumor markers were elevated, abemaciclib(300 mg/day)was added, which resulted in a decrease in the tumor markers...During the course of treatment, the tumor markers rose again, so the dose was increased to 250 mg/day, which resulted in a decrease in the tumor markers and good tolerability. At present, 36 months after the start of treatment, long SD has continued, no adverse events of grade 3 or higher have been observed, and the drug has been well tolerated.

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 utilized MR methods to analyze potential causal relationships between various antibody immune responses, immune cell types, and BC subtypes, identifying four potential regulatory mediation pathways. The findings of this study offer potential targets and research directions for virus-related and immunotherapy-related studies, providing a certain level of theoretical support. However, limitations such as GWAS sample size constraints and unclear specific pathophysiological mechanisms need further improvement and validation in future studies.

P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2024 --> Mar 2026 | Trial primary completion date: Aug 2024 --> Mar 2026

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.

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.

P3, N=1684, Active, not recruiting, West German Study Group | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

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.

P2, N=52, Completed, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Unknown status --> Completed | N=150 --> 52

P1, N=17, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=48, Suspended, City of Hope Medical Center | Recruiting --> Suspended

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.

Together, the results suggest that mRNA expression of ESR1, ESR2, and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.

P3; In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.

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.

Among breast cancer patients with pT2N0, cM0 ER+/HER2- tumors, 20% had a RS<11. All these patients based on the AJCC 8th Edition Cancer Staging Manual are assigned Pathological Prognostic Stage Group IA. These patients based on TAILORx data have 0,7% distant recurrence risk at 5 years, 3% distant recurrence risk at 9 years and no chemotherapy benefit.

Here we report the primary endpoint of complete cell cycle arrest (CCCA) and correlative studies of the NeoPalAna (NCT01723774) ET-R Cohort to examine resistance biomarkers for palbociclib (PAL) + anastrozole (ANA). Specific oncogenic pathways and immune tolerance markers, such as IDO1, were enriched in PAL-R. Our data also suggest immune modulatory effects of CDK4/6i/ET in association with ET/PAL response.

HR-Low and HR-Int HER2-negative BC are rare subtypes with distinct biologic features compared to HR-High BC. This real-world analysis reveals significant differences in the survival outcomes, management, and treatment responses of HR-Low and HR-Int BCs. ET use is less common with lower HR expression yet associated with improved 5y OS.

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.

Linearity testing, where the cell lines were spiked in 7.5mL blood, showed high levels of reproducibility across the clinical range (1000 cells to 0) with an R2 = 0.99. The CELLSEARCH® CTC-HER2 Low test meets a critical clinical need that breast cancer patients, positive or classified as negative from a tissue biopsy, in need of a current evaluation of their metastatic breast cancer HER2 status, through any line of treatment, can do so from one blood draw using a test that can detect HER2 expression to very low levels.

Conclusion The OncoSIGNal test provides a robust and quantitative method to characterize low ER and HER2 1+ IHC breast cancer samples. In addition to detecting and quantifying the relevant cell signaling pathways, the mRNA markers can be used to elucidate the results of low ER and HER2 1+ IHC staining, enabling the identification of patients who may benefit from targeted therapy.