We summarize intensive treatment methods for T1N0M0 HR+/HER2- breast cancer patients, which extend beyond the standard 5-year tamoxifen (TAM)-based adjuvant ET. These methods include intensive ET, poly(ADP-ribose) polymerase (PARP) inhibitors, other targeted therapies, antibody-drug conjugates, oral chemotherapy, immunotherapy, and enhanced prevention of bone metastasis. This review provides a foundation for developing personalized adjuvant treatment strategies for patients with T1N0M0 HR+/HER2- breast cancer.

GR-driven gene programmes are selectively activated in in vivo models of ERα-positive breast cancer during fasting, and GR knockout hinders the anti-tumour effects of fasting combined with tamoxifen...Additionally, tumours collected after the fasting-mimicking diet showed an inverse correlation of GR activation with proliferation markers, providing clinical confirmation of our observations in animal models. Our results indicate that GR activation has a pivotal role in the ability of fasting to enhance endocrine therapy activity in breast cancer and suggest that corticosteroid administration should be evaluated as an adjuvant to endocrine therapy in this setting.

P=N/A, N=10, Terminated, University of Pennsylvania | N=128 --> 10 | Trial completion date: Dec 2026 --> Nov 2025 | Enrolling by invitation --> Terminated | Trial primary completion date: Dec 2026 --> Nov 2025; Lack of funds

Our results highlight that BKCa "oncochannels" may modulate the response of BC cells to TAM+M. Activation of the TAM+M-BKCa axis causes significant changes in K+ and Ca2+ ion homeostasis, which ultimately contributes to the outcome of endocrine-based BC pharmacotherapy.

Furthermore, the tamoxifen-inducible loss of FGFR1/2 signaling during adulthood also impaired LTP. In addition, the conditional ablation of either FGFR1 or FGFR2 individually in the OL-lineage cells impaired LTP during adulthood, although at different levels. Thus, these observations bring up the possibility that FGFR1/2 signaling in OL-lineage cells may play a potentially novel, previously unrecognized role in OL-neuron communication for the maintenance of synaptic plasticity and memory functions in the normal adult/aging brain.

AGL showed significant anticancer activities on LA7 cells, with a potency similar to tamoxifen, an FDA-approved drug for BC...Morphological analysis by light and scanning electron microscopy (SEM) showed no observable changes in structural integrity of RBC membranes indicating nonhemolytic nature of AGL. Our results suggested that AGL has significant potential to be explored as an anticancer agent in BC therapy without any RBC toxicity.

Additionally, nano-curcumin induces apoptosis and inhibits migration. These findings suggest the nano-curcumin and tamoxifen combination may be a promising therapeutic strategy to overcome drug resistance in ER+ breast malignancies.

The observed effect was ESR1-dependent and effectively blocked by tamoxifen, revealing a ligand-independent activation mechanism...The presence of PSNPs also mitigated AgNPs-induced reduction of BRCA1 expression. This study highlights how nanomaterial-induced ESR1 activation can lead to enhanced epithelial-mesenchymal transition and cell cycle progression, suggesting potential adverse effects of nanomaterials in ER+ cancer proliferation via protein kinase-mediated ESR1 modulation.

We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations and promotes tamoxifen resistance in nuclear ER/PR transcriptional complexes...The UPR activator ErSO, but not UPR inhibitors, blocked expansion of CSCs in WT as well as Y537S ER + models. Together, our findings demonstrate a critical interplay between PR and mutant ER function and provide insight into PR-driven pathways including hyperactivation of the stress-sensing UPR that can be exploited as potential therapeutic avenues in advanced ER+ breast cancer.

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting

Finally, we identified a resistance and stemness marker signature induced by CPF+TAM that closely resembles the profile observed in the dataset of patients who acquired TAM resistance. Our findings show that CPF promotes an undifferentiated basal-like cell phenotype that contributes to TAM resistance, reinforcing the need for global restrictions to safeguard public health.

Inhibition of the RAD51B-EZH2 axis allows the re-expression of functional ERα, making TNBC targetable by endocrine therapy. Consistently, the combination of EZH2 inhibitor with tamoxifen effectively reduces TNBC progression, suggesting that the RAD51B-EZH2 axis is a potential therapeutic target for TNBC.