P-cadherin as prognostic factor for loco-regional relapse in breast cancer.

Abstract

Breast cancer is the most frequent malignant tumor and the leading cause of cancer death in women in Portugal. Due to its relation to an increase in distant metastasis and subsequent death, loco-regional relapse is one major concern in breast cancer women. Several classic prognostic factors as tumour size, nodal stage, histological grade, HER2 status and hormonal receptors have been identified as the most important factors for determining loco-regional relapse, disease free and overall survival. However, there is heterogeneity in prognosis and tumor behaviour in patients with identical disease staging and a similar pattern of expression of known molecular markers, hence the need to discover new prognostic factors. One of the possibilities is P-cadherin, already described by researchers as a possible independent marker of prognosis in breast cancer. The aim of this work was to study in a retrospective series of patients the correlation of P-cadherin expression with loco-regional recurrence in breast cancer women. We analyzed the clinical records of 1432 consecutive patients with breast cancer and treated in a University Hospital over a 10 year period. Patients with loco-regional relapse (n=101) without prior or simultaneous distant disease were selected as case group. Control group consisted of patients with more than 10 years follow-up and without disease progression. For both groups demographic, clinical, pathological and molecular markers were analyzed. Tissue micro-arrays were constructed to study P-cadherin expression from 86 tumors with available paraffin embedded blocks. Mean time to recurrence was 41 months and mean survival time after recurrence was 33 months, with a 5-year survival rate of 55%. Tumour size, nodal status and histological grade were identified as independent markers of prognosis. P-cadherin was associated with higher histological grades and hormone negative tumours. P-cadherin was identified as an independent prognostic marker for disease free survival, but not for overall survival. P-cadherin was related to other known factors of worse prognosis and had an independent relation to disease-free survival. P-cadherin might constitute a novel therapeutic target, but its real biological value is yet to be determined. Doubt persists whether it is an independent marker of tumour behaviour or only a surrogate marker of a set of clinical and molecular features related with worse prognosis.