Best treatment for metastases in a patient with ER-positive, PR-negative, HER2-negative breast cancer after hormonal therapy failure?

• A. Cytotoxic chemotherapy
• B. Further hormonal therapy
• C. Immunotherapy
• D. Radiation therapy

Answer: (A)

When metastatic breast cancer remains ER-positive but loses control after endocrine therapy, the next systemic option is cytotoxic chemotherapy. Endocrine therapies cut off the tumor’s hormone signaling, but resistance often develops, especially in metastatic disease. Chemotherapy works independently of hormone receptor signaling and can produce more rapid and substantial tumor reduction, which is most important when the disease is progressing. In this setting, agents such as taxanes or anthracyclines are commonly used to achieve systemic control and palliate symptoms.

Radiation therapy would be reserved for focal, local control rather than treating widespread metastases. Immunotherapy isn’t a standard frontline choice for this receptor profile. Continuing the same hormonal approach after progression is less effective, and while newer targeted endocrine strategies exist, the typical next step for progression after hormonal therapy in ER-positive, HER2-negative disease is cytotoxic chemotherapy.