HER2 Negative Breast Cancer

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.

P=N/A, N=37, Not yet recruiting, Pfizer

P3, N=500, Recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Jun 2026 --> Apr 2028 | Trial primary completion date: Jun 2025 --> Apr 2027

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.

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.

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.

P2, N=333, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

CDK4/6 inhibitors such as palbociclib block cell cycle progression and improve outcomes for many ER+/HER2- breast cancer patients...Understanding the molecular mechanisms that allow treated tumor cells to evade arrest is critical for identifying targets of future therapies. Ultimately, we seek to further SPCA as a tool of precision medicine, targeting treatments by individual tumors, and extending this computational framework to interpret other cyclical biological processes represented by high-dimensional data.

P=N/A, N=419, Completed, MedSIR | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> May 2024

P1/2, N=40, Recruiting, Centre de recherche du Centre hospitalier universitaire de Sherbrooke

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

Knockdown of NSRP1 reduces CDK4/6i (palbociclib) sensitivity of MCF7 cells while overexpression of NSRP1 sensitizes MCF7-PalR cells towards palbociclib treatment...In addition, including NSD2 exon 2 elevates NSD2 protein expression to activate the IFN signaling pathway. This study unveils the critical role of NSRP1 in regulating the IFN signaling pathway and the CDK4/6i resistance, which could be a promising biomarker for predicting therapy response.

There is an important percentage of Hispanic/Latino individuals who would benefit from HER2-targeted therapies, even in HER2 negative cases. Additional research on the prevalence of HER2-low tumors across a wider range of Latin American countries is required to better understand the molecular epidemiology of this biomarker within the Hispanic/Latino population.

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.

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

P2, N=130, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Sep 2024

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.

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.).

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=25, Recruiting, Amsterdam UMC, location VUmc | Not yet recruiting --> Recruiting

P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025

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.

P1/2, N=280, Not yet recruiting, Novartis Pharmaceuticals

P3, N=240, Recruiting, MedSIR | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024

P2, N=30, Recruiting, Beijing 302 Hospital | Not yet recruiting --> Recruiting | Initiation date: May 2024 --> Oct 2024

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.

These tools take into consideration the histopathologic parameters and immunohistochemistry (IHC) biomarkers data for estrogen receptor/progesterone (ER/PR), human epidermal growth factor receptor 2 (HER2), and Ki67...No significance was noted across different prediction tools. The findings are suggestive that ME predictive scores are more relevant and informative compared to other online tools and with an additional AR IHC expression analysis the recurrence prediction might prove to be beneficial and feasible to many deprived BC patients.

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.

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=65, Recruiting, Menarini Silicon Biosystems, INC | Trial completion date: Dec 2024 --> Aug 2026

P2, N=120, Active, not recruiting, University of California, Irvine | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P=N/A, N=60, Recruiting, European Institute of Oncology

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

P3, N=463, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Jan 2026

Decision curve analysis demonstrated its potential clinical utility. A biplanar ultrasound radiomics nomogram effectively predicts HER2 status in invasive BC, potentially reducing the need for biopsies and supporting personalized treatment strategies.

The efficacy and safety profiles of neoadjuvant pembrolizumab plus chemotherapy in the Japanese population are consistent with previous reports. This regimen may have therapeutic potential against ER-low HER2-negative tumors and TNBC.