Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study

Abstract

Background: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA.

Methods: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records.

Results: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]).

Conclusions: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.

Keywords: Breast cancer; Microangiopathic haemolytic anaemia; Prognostic factors; Survival.

Fig. 1

Study flow chart

Fig. 2

Overall survival according to independent prognostic factors. a Overall survival in all patients. b Overall survival by prothrombin time. c Overall survival by performance status. d Overall survival by total bilirubin level. d Overall survival by haemoglobin

Fig. 3

Breast cancer MAHA survival predictive score. a predictive score of death within 28 days after MAHA diagnosis, according to observed outcome. b Predictive score according to the observed outcome. c ROC curve. Area under the curve (AUC = 0.90 (95% CI [0.83; 0.97]). Sensitivity for early death of 0.86 (95% CI [0.67; 0.96]). Specificity for early death of 0.73 (95% CI [0.62; 0.88])