PITX2 DNA-methylation as the first clinically validated predictive marker for anthracycline based chemotherapy in high-risk breast cancer patients

International guidelines recommend anthracycline-based chemotherapy for high-risk breast cancer patients as the standard-of-care, but not all patients do equally benefit from such a chemotherapy. The novel therascreen® PITX2 RGQ PCR assay is a quantitative in vitro methylation-specific real-time PCR test (qMSP), intended for the determination of the percent methylation ratio (PMR) in the pituitary homeobox 2 (PITX2) promoter 2 expressed by primary breast cancer tumor tissue (FFPE-material). After bisulfite exposure of extracted DNA to distinguish between methylated and non-methylated PITX2 DNA, the percent methylation ratio (PMR) of the PITX2 gene promoter 2 is quantified by qMSP. The PMR obtained does provide information to the treating physician about whether a patient is likely to respond to anthracycline-based chemotherapy. Data will be presented for 205 high-risk lymph node-positive, estrogen receptor-positive, HER2-negative breast cancer patients, treated with adjuvant anthracycline-based chemotherapy. The PITX2 pre-defined cut-off value of PMR = 12 demonstrated a statistically significant differentiation between low- and high-risk breast cancer patient for the primary endpoint DFS, also for patients treated with endocrine therapy in addition to anthracycline-based adjuvant therapy. High-risk lymph node-positive, estrogen-receptor-positive, HER2-negative breast cancer patients, with PITX2 methylation defined as low (PMR ≤ 12), are sufficiently treated with anthracycline-based chemotherapy, irrespective if treated with additional tamoxifen. High-risk lymph node-positive, estrogen receptor-positive, HER2-negative breast cancer patients with PITX2 methylation defined as high (PMR > 12) should avoid anthracycline-based chemotherapy. These patients are recommended to switch to other chemotherapy regimens, since with this PITX2-characteristics, the patient has a lower probability to respond to anthracycline-based chemotherapy.