What happened, in summary

A 41-year-old woman with Shwachman-Diamond syndrome developed invasive ductal carcinoma of the left breast. Her underlying syndrome included lifelong thrombocytopenia without bleeding, prior pancreatic insufficiency, arthralgias, short stature, femoral chondrodysplasia, and SBDS variants c.258+2T>C and R126T. She had no known marrow dysplasia, and MyeloSeq testing did not detect variants in 49 assessed genes, including TP53. Breast imaging found a 2 cm triple-positive tumor, meaning ER-positive, PR-positive, and HER2-positive. PET/CT also identified a 2.0 x 2.2 cm liver lesion, and biopsy confirmed metastatic breast cancer, giving a stage of pT2 N1 M1. Because of concern for myelosuppression from her underlying condition, weekly paclitaxel was chosen instead of docetaxel, with trastuzumab and pertuzumab every 21 days. Paclitaxel was briefly held after early chemotherapy-induced neutropenia, and filgrastim/G-CSF was added when the absolute neutrophil count fell below 1,500 cells/mm3. She continued treatment with twice-weekly G-CSF support and did not develop severe infections. After 6 cycles, CT of the chest, abdomen, and pelvis showed no evidence of metastatic disease, although a catheter-associated internal jugular vein thrombus led to apixaban. After 9 cycles, CT confirmed a complete response. Paclitaxel was stopped because of peripheral sensory neuropathy, and she transitioned to maintenance trastuzumab plus pertuzumab every 3 weeks. She also started anastrozole and goserelin; tamoxifen was avoided because of the catheter-associated thrombus. As of 18 months after treatment began, she had maintained a complete response with ongoing blood-count monitoring. Treatment-related diarrhea was controlled with loperamide and diphenoxylate/atropine, oral mucositis was treated with mouthwash, and cardiac function was preserved.