Objective:

To explore the challenges and strategies in managing ER/PgR low-expression breast cancer through a comprehensive multidisciplinary approach, emphasizing collaboration across specialties.

Key Findings:

• Current ASCO/CAP 1% positivity threshold does not capture the heterogeneity of ER/PgR low-expression breast cancer, leading to potential mismanagement.
• Approximately 75-80% of ER-low tumors are non-luminal and basal-like, with outcomes resembling TNBC, indicating a need for tailored treatment strategies.
• Low PgR combined with high Ki67 is significantly associated with HER2 overexpression, suggesting a potential target for therapy.
• Eribulin chemotherapy and PD-1/PD-L1 inhibitors show promise in treating advanced breast cancer, including ER-low cases, warranting further investigation.
• Novel drug delivery strategies, such as myricetin nanoemulsion, demonstrate enhanced anti-tumor activity, highlighting innovative therapeutic avenues.

Interpretation:

ER/PgR low-expression breast cancer requires a biologically informed approach that integrates molecular subtyping and immune profiling for effective management.

Limitations:

• The current classification systems inadequately address the complexities of ER/PgR low-expression breast cancer, potentially leading to suboptimal treatment.
• There is a need for standardized biomarker assessment and prospective trials specifically targeting ER-low patients to validate findings and improve clinical outcomes.

Conclusion:

A biologically grounded approach is essential for improving outcomes in ER/PgR low-expression breast cancer, with dedicated prospective trials as a priority, reinforcing the importance of a multidisciplinary strategy.