Relapsing Phospholipase A2 Receptor Antibody-Positive Membranous Nephropathy as a Marker of Metastatic Recurrence of Breast Cancer: A Case Report

Introduction: Phospholipase A2 receptor-1 antibodies (PLA2RAb) are key drivers of membranous nephropathy (MN) and testing is a cornerstone in diagnosing MN. There is a recognised correlation between solid organ malignancy and secondary MN. Here we provide a fascinating update on a previously reported case of breast cancer-associated PLA2RAb positive MN. Case Description: In a previous report of this case, a woman presenting with nephrotic syndrome was diagnosed with MN, with positive serum PLA2RAb and positive PLA2RAb staining on renal biopsy. She was later found to have breast cancer treated with mastectomy and axillary node clearance, adjuvant AC chemotherapy and radiotherapy and maintenance tamoxifen. Following treatment, there was an improvement in her oedema, albumin (16 g/L to >35 g/L) and PLA2RAb titres (674 kU/L to <2kU/L). Her urine protein:creatinine ratio (uPCR) improved from 1400 mg/mmol, stabilising at 200-250 mg/mmol. It was speculated that the PLA2RAb production and MN was driven by the breast cancer and thus remission was induced by treatment of the underlying malignancy. She was discharged by oncology to patient-initiated follow up, with annual surveillance mammography. She remained in clinical remission for five years, before presenting with oedema, an albumin of 25 g/L and rise in PLA2RAb to 12 kU/L (subsequently rising to 188 kU/L). uPCR rose to 1443 mg/mmol. A whole body FDG PET scan identified areas of high uptake in the spine with biopsy confirmation of metastatic breast carcinoma. Anti-cancer treatment with ribociclib, letrozole and denosumab was commenced and she was given two doses of Rituximab 1g by the renal team. With this, we saw improvement in her symptoms and albumin (35 g/L), although with a persistent proteinuria (uPCR >800 mg/mmol). PLA2RAb levels improved promptly following the initiation of anti-cancer therapy, falling to 85kU/L (prior to starting Rituximab) and were persistently < 10kU/L thereafter. A repeat PET scan has shown a complete metabolic response. Discussion: This update appears to confirm the link between breast cancer and PLA2RAb positive MN in this patient. It also demonstrates partial remission of MN by treating the underlying malignancy (without the use of cyclophosphamide) and a unique report of relapsing pLA2RAb positive MN prompting the diagnosis of metastatic disease recurrence.