The Predictive Value of PITX2 DNA Methylation for High-Risk Breast Cancer Therapy: Current Guidelines, Medical Needs, and Challenges

Table 5

Importance and clinical relevance of PITX2 DNA methylation status for various types of cancer.

Cancer type	Adjuvant treatment	Clinical endpoint	Clinical impact analyzed	Reference
Breast cancer (); LN−, ER/PR+	Tamoxifen	MFS	Therapy response prediction	Maier et al., 2007 [51]
Breast cancer (); LN−, ER/PR+	None	TDM, OS	Prognosis	Nimmrich et al., 2008 [48]
Breast cancer (); LN−, HER2±, ER/PR+	Tamoxifen	TDM	Therapy response prediction	Harbeck et al., 2008 [65]
Breast cancer (); LN+, ER/PR+	Anthracycline	DFS, MFS, OS	Therapy response prediction	Hartmann et al., 2009 [44]
Breast cancer (); LN±, ER/PR±, HER2±	Chemotherapy: 65% of the patients. Endocrine therapy: 39% of patients	OS, DFS, DSS	Prognosis	Buhmeida et al., 2011 [74]
Breast cancer (); LN±, ER/PR±, HER2±	Not disclosed	No follow-up	Association of PITX2 with RASSF1A and clinicopathological parameters	Jezkova et al., 2016 [64]
Breast cancer (); LN±, ER/PR/HER2−	Anthracycline	DFS	Therapy response prediction	Absmaier et al., 2017 [66]
Prostate cancer ()	Observation, untreated	OS	Prognosis	Ahmad et al., 2016 [75]
Prostate cancer ()	Observation, untreated	Biochemical recurrence	Prognosis	Bañez et al., 2010 [76]
Prostate cancer ()	Not disclosed	Biochemical recurrence	Prognosis	Uhl et al., 2017 [77]
Prostate cancer ()	Observation, untreated	Biochemical recurrence	Prognosis	Dietrich et al., 2013 [78]
Prostate cancer ()	Observation, untreated	Biochemical recurrence	Prognosis	Vasiljević et al., 2014 [79]
Prostate cancer ()	Observation, untreated	Biochemical recurrence	Prognosis	Litovkin et al., 2014 [80]
Prostate cancer ()	Not disclosed	Biochemical recurrence	Prognosis	Vinarskaja et al., 2013 [81]
Biliary cancer ()	Not disclosed	OS	Prognosis	Uhl et al., 2016 [82]
Esophageal cancer ()	Chemoradiotherapy including cisplatin plus 5-fluorouracil	DFS	Prognosis; Therapy response prediction	Zhang et al., 2013 [83]
Pancreatic cancer ()	Not disclosed	OS	Prognosis	Wang et al., 2016 [84]
Head & neck cancer ()	Radiotherapy ± chemotherapy	OS, DFS	Prognosis	Sailer et al., 2016 [85]
Head & neck cancer ()	Not disclosed	OS	Prognosis	Sailer et al., 2017 [86]
Lung cancer (NSCLC) ()	± radiotherapy/chemotherapy	PFS	Prognosis	Dietrich et al., 2012 [87]

DFS: disease-free survival; DSS: disease-specific survival; OS: overall survival; PFS: progression-free survival; TDM: time to distant metastasis; MFS: metastasis-free survival; LN: lymph node status; ER/PR: receptors for estrogen and/or progesterone; HER2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer.