Cold agglutinin syndrome in a patient with metastatic breast cancer: a Case Report.

Background: Cold agglutinin syndrome (CAS) is a form of autoimmune hemolytic anemia (AIHA), most often associated with lymphoproliferative disorders or infections. Its occurrence in breast cancer is rare and may be triggered by systemic treatment. Case presentation: We report the case of a woman in their fifties diagnosed with breast cancer in 2019. She underwent surgery followed by adjuvant chemotherapy and radiotherapy and subsequently received 3 years of endocrine therapy before developing bone and hepatic metastases. First-line treatment with ribociclib plus letrozole achieved partial response, and fulvestrant was administered at progression. Following further progression, paclitaxel was introduced as third-line metastatic therapy. After four weekly administrations, the patient was admitted to our hospital with severe anemia and diagnosed with CAS. Prompt management and a multidisciplinary approach resulted in partial hematological recovery. Nevertheless, paclitaxel was permanently discontinued, and subsequent therapies provided only transient benefit. The disease continued to progress, her performance status declined, and she ultimately transitioned to exclusive palliative care until death. Conclusion: This case illustrates a rare and severe immune complication of paclitaxel in metastatic breast cancer. The emergence of CAS not only limited systemic options but also reshaped the therapeutic trajectory, highlighting the need for close monitoring during cancer treatments. Early recognition, multidisciplinary approach, and prompt management can provide some improvement, although overall prognosis remains determined by the underlying malignancy.