MDM2 polymorphisms and hematological parameters during chemotherapy
All samples were drawn from patients treated for large primary breast cancers as part of a phase II investigator-initiated single arm study applying dose-dense (2-weekly) treatment with 4 cycles of epirubicin (60mg/m2) followed by 4 cycles of docetaxel (100mg/m2) conducted at Haukeland University Hospital between 2007 and 2016 (Dose Dense Protocol [DDP]; NCT00496795). The trial enrolled 109 patients with non-inflammatory, primary breast cancers with a tumor size >4 cm and/or N2-3 regional lymph node metastases. All patients received bone marrow support, G-CSF (NeulastaÒ; pegfilgrastim) as a 6 mg subcutaneous injection 24-48 hours after each chemotherapy cycle. For details on included/excluded patients in the present study, see the “Methods” section of (1).
All included patients were genotyped for three functional polymorphisms in MDM2: SNP309 T>G (rs2279744; GRCh38: chr12:68808800, SNP285 G>C (rs117039649; chr12:68808776) and del1518 ins/del40 (rs3730485; chr12:68807065), in blood samples drawn prior to treatments. For details see the “Methods” section of (1).
Additional blood samples were drawn and analyzed for hematological parameters before each of the eight chemotherapy cycles. We assessed longitudinal ratios of neutrophil cell counts as our main measure. This table also includes our secondary measures (longitudinal ratios of total leukocyte cell counts, thrombocyte counts and hemoglobin values).
We defined the ratio of change in cell count during epirubicin treatment (Repi) as cell count in blood samples before chemotherapy cycle 5 (first cycle of docetaxel) divided by the corresponding count before cycle 1 (baseline value, prior to any chemotherapy). The ratio of change in cell count during docetaxel treatment (Rdoc) was defined as cell count in blood samples before cycle 8 of chemotherapy divided by the corresponding count before cycle 5. The ratio of change over the total neoadjuvant treatment (Rtot) was defined as cell count before cycle 8 divided by the corresponding count before cycle 1.
1. Venizelos A, Engebrethsen C, Deng W, Geisler J, Geisler S, Iversen GT, et al. Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy. Genome Medicine. 2022 Aug 11;14(1):86.
