Metastatic breast cancer with receptor evolution: sequential endocrine, immunotherapy, CDK4/6, and antibody-drug conjugate treatment

What happened, in summary

This 52-year-old woman first presented with a tender self-palpated left breast mass and skin changes. Imaging showed a large irregular tumor with nipple retraction and skin thickening. Core biopsy confirmed high-grade invasive ductal carcinoma that was ER-positive over 90%, PR below 5%, HER2 IHC 0/FISH-negative, PD-L1 CPS 1, and Ki-67 over 20%. Axillary lymph node biopsy showed metastatic adenocarcinoma from the breast, and staging was cT4N1M0, Stage IIIA. Initial treatment included neoadjuvant AC chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel, bilateral mastectomy with implants, and radiation. Pathology showed a 9.2 cm high-grade tumor with lymphatic invasion and 3 of 11 nodes involved. She then received endocrine therapy, first anastrozole and then letrozole. Four years into endocrine therapy, skin changes near the surgical scar led to biopsy showing triple-negative transformation, HER2-low IHC 1+/FISH-negative, and PD-L1 CPS 10. She received pembrolizumab with weekly carboplatin/paclitaxel, then surgical excision, chest wall radiation, pembrolizumab, and capecitabine, which stopped early because of mucositis. Six years after diagnosis, mediastinal nodes showed metastatic breast cancer with ER returning over 80%, leading to fulvestrant plus ribociclib and 1 year of stability. Later pleural fluid suggested metastatic breast cancer with ER loss, and sacituzumab govitecan was started for presumed triple-negative disease. Three months later, imaging and clinical assessment showed at least a partial response. Her treatment path changed repeatedly as biopsies showed receptor shifts over time, allowing each new systemic therapy to match the most recent tumor biology and clinical disease pattern over time.