# Recurrent severe thrombocytopenia induced by anti-HER2 therapy in a breast cancer patient with an underlying immune disorder: a case report and literature review

## TL;DR

A breast cancer patient developed severe, recurring low platelet counts during anti-HER2 therapy, likely due to an underlying immune disorder.

## Contribution

This case highlights a rare immune-mediated side effect of anti-HER2 therapy linked to preexisting autoimmune markers.

## Key findings

- Trastuzumab and pertuzumab (including subcutaneous forms) can induce immune-mediated thrombocytopenia.
- Thrombopoietin-stimulating agents and immunomodulatory therapy partially managed the condition.
- Underlying autoimmune serology, such as ANA and anti-SSA/Ro52 antibodies, may heighten the risk.

## Abstract

This case report describes a 51-year-old female with HER2-positive breast cancer who developed recurrent, severe thrombocytopenia during treatment with trastuzumab and pertuzumab. Through a retrospective analysis of her entire treatment course—encompassing neoadjuvant, adjuvant, and radiotherapy phases—we dynamically observed the temporal correlation between anti-HER2 therapy administration and acute drops in platelet count (nadir: 8×109/L), accompanied by bleeding symptoms. The thrombocytopenia responded well to thrombopoietin-stimulating agents and immunomodulatory therapy but recurred persistently, even after switching to trastuzumab monotherapy or its subcutaneous formulation. Laboratory workup was notable for revealing a predisposition to undifferentiated connective tissue disease (UCTD) with positive antinuclear antibody (ANA) and positive anti-SSA/Ro52 antibodies. Ultimately, all targeted therapies were discontinued due to intolerability. This case highlights that both trastuzumab and pertuzumab (including subcutaneous forms) can induce rare immune-mediated thrombocytopenia, a risk significantly heightened by underlying autoimmune serology. The mechanisms appear multifactorial, involving the patient’s immune status, treatment phase, and route of administration. It underscores the need for heightened clinical vigilance, prompt drug suspension, supportive care, and individualized, multidisciplinary management in such scenarios.