Triple-negative breast cancer with pathologic complete response after neoadjuvant chemoimmunotherapy complicated by immune toxicity

What happened, in summary

This 45-year-old woman had triple-negative breast cancer staged cT3N1M0, Stage IIIA. In March 2024, she began neoadjuvant nab-paclitaxel, carboplatin, and pembrolizumab. After 2 well-tolerated cycles, she had a clinical partial response. Baseline evaluation had also shown a right parathyroid mass with mild hypercalcemia and elevated intact parathyroid hormone, suggesting parathyroid dysfunction. During cycle 3, she developed severe multisystem toxicity: grade 4 drug-induced liver injury, fever, grade 2 rash, leukopenia, severe headache, vomiting, hypertension, MRI findings of diffuse leptomeningeal enhancement, and cerebrospinal fluid findings consistent with immune-related meningeal inflammation rather than malignant cells. Hypercalcemia worsened into a crisis, and the parathyroid mass enlarged. Emergency treatment included salmon calcitonin, zoledronic acid, and fluid resuscitation. On May 22, she underwent right parathyroidectomy, which confirmed parathyroid adenoma and normalized calcium and parathyroid hormone levels. Because the timing linked the hepatic, neurologic, skin, and metabolic events to immunotherapy, pembrolizumab was stopped in May 2024. She continued nab-paclitaxel and carboplatin for 4 cycles. A brain MRI on June 3 showed complete resolution of meningeal thickening. Five-month follow-up showed no residual major sequelae, and left mastectomy on November 17 confirmed pathologic complete response. Her cancer treatment therefore had to continue while the care team managed endocrine and immune toxicities at the same time. The neurologic episode was especially important because the MRI suggested inflammation around the meninges, but cerebrospinal fluid did not show malignant cells. Corticosteroids and antihistamines gradually resolved the rash, and parathyroid surgery addressed the driver of the hypercalcemia. Liver tests had partially improved before the later neurologic and metabolic crisis, which helped separate overlapping toxicities from persistent cancer activity.