Cancer-related microangiopathic haemolytic anemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only case reports or very small series (<5-10 cases) with mixed cancer types have been been reported so far. We conducted the first retrospective multicenter study focusing on breast cancer related-MAHA (BC-MAHA).
13 centers in France were contacted for this retrospective study in patients treated for BC over the past 20 years. Presence of schistocyte and either low haptoglobin or cytopenia was mandatory to retain the diagnosis of MAHA. MAHA from other causes than BC were excluded, as well as patients treated with gemcitabine or bevacizumab prior to MAHA diagnosis. Patient characteristics, treatments and outcome were retrieved from digital medical records.
Individual data from 54 patients with BC-MAHA were obtained from 7 centers. 23 (44%) patients had a lobular BC and most BC were of low grade (grade I/II, N = 39, 75%). 33 (69%) primary BC were ER+/HER2- whereas 7 (15%) were HER2+ and 8 (17%) triple negative. At MAHA diagnosis, all 54 patients had a stage IV cancer, 32 (59%) had ≥3 metastatic sites. Median overall survival (OS) was 28 days (range: 0-1035; Q1:10, Q3:186). In univariate logistic regression analysis performed after imputation of missing data with MICE procedure, PS >2 (OR = 6.0, CI95% [1.8; 19.8]), one or more prior lines of treatment (OR = 2.9, [0.9; 8.7]), elevated bilirubin (OR = 5.5, [1.5; 20.6]), haemoglobin <80g/L (OR = 4.0, [1.35; 12.0]), and prothrombin ratio <50% (OR = 7.1, [0.9; 50.0]) were associated with a higher risk of death within 4 weeks of MAHA diagnosis. In multivariate analysis, PS >2 (OR = 6.1, [1.4; 25.9]), elevated bilirubin (OR 4.7, [1.0; 24.0]), haemoglobin <80g/L (OR = 4.0, [0.9; 16.7]) and prothrombin ratio <50% (OR = 11.1, [1.06; 100.0]) remained associated with a higher risk of death within 4 weeks of MAHA diagnosis.
This study is the first attempt at characterizing BC-MAHA, which appears to be more frequent in the lobular subtype. In spite of a dismal median OS, a few patients experienced long-term survival and we document, for the first-time, prognostic factors that may guide therapeutic decision making.
François-Clément Bidard (Institut Curie, Paris, France).
Has not received any funding.
F.C. Bidard: Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Menarini Silicon Biosystems; Speaker Bureau / Expert testimony: Amgen. P. Heudel: Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Sandoz; Travel / Accommodation / Expenses: Roche. J. Pierga: Honoraria (institution), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (self): illumina; Honoraria (self), Research grant / Funding (self): Genomic Health; Honoraria (self), Research grant / Funding (self): puma; Honoraria (self), Research grant / Funding (self): Celltrion; Honoraria (self), Research grant / Funding (self): sandoz; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Ipsen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): jansen diagnostics; Research grant / Funding (institution): menarini silicon biosystems; Research grant / Funding (institution): bms; Research grant / Funding (institution): MSD; Research grant / Funding (institution): daiichi senkyo; Research grant / Funding (institution): Servier. S. Delaloge: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: astrazeneca; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): puma; Advisory / Consultancy, Research grant / Funding (institution): orion; Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Amgen. J. Frenel: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: bio cad; Advisory / Consultancy: astrazeneca; Advisory / Consultancy: Lilly; Honoraria (institution): Novartis. C. Levy: Advisory / Consultancy, Travel / Accommodation / Expenses: astrazeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: biogaran; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.