Hormone Sensitivity in Cancer Treatment

Understanding Hormone Receptor Status

• The American Society of Clinical Oncology recommends hormone receptor status (ER/PR expression by immunohistochemistry) as the defining factor for hormone sensitivity, not PIK3CA or ESR1 mutations 1, 2
• Re-biopsy of metastatic sites should include ER, PR, and HER2 testing because receptor status can change between primary and metastatic disease, with discordance rates ranging from 3.4% to 60% for ER status 1, 2

Determining Treatment Eligibility

• PIK3CA mutations guide treatment selection, such as alpelisib eligibility, in already confirmed HR-positive disease, but do not define hormone sensitivity 3, 4
• ESR1 mutations indicate endocrine resistance mechanisms and may guide choice between aromatase inhibitors versus fulvestrant, but do not determine if the tumor is hormone-sensitive 4, 5

Testing Algorithm for Recurrent Disease

• The National Comprehensive Cancer Network recommends always re-testing ER, PR, and HER2 on metastatic tissue when feasible to confirm the tumor remains hormone-sensitive 1, 2
• PIK3CA testing is indicated if the tumor is confirmed HR-positive/HER2-negative to determine alpelisib eligibility, using a reflex approach with plasma ctDNA first, followed by tissue testing if negative 3, 6

Additional Biomarkers and Pitfalls

• Germline BRCA1/2 testing should be performed if considering PARP inhibitor therapy, as it is critical for treatment planning 8
• Up to 31% of tumors change ER status from positive to negative between primary and metastatic sites, highlighting the importance of re-biopsy 2
• Only 56% concordance exists between plasma and tissue PIK3CA testing, emphasizing the need for tissue testing if plasma is negative 3, 6, 9