Breast cancer and neoadjuvant therapy: any predictive marker?

The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. However, the effect of cytotoxic treatment cannot be predicted on individually specific basis, then identification of tumor characteristics associated with tumor therapeutic response and outcome is then of great clinical interest. We studied 141 patients at Masaryk Memorial Cancer Institute, who received neoadjuvant chemotherapy and/or chemotherapy + radiotherapy (CHT/CHT+RT) between 1994-2002. Tumor samples were taken prior to and after neoadjuvant therapy. We quantified the response to therapy pathologically and determined histological and molecular tumor characteristics (steroid receptors, CEA, Ca 15-3). In addition to therapeutic response as immediate outcome, event free survival (EFS) was examined as more complex primary end-point of the study. Complete remission (CR) has been achieved in 6.5%, partial remission (PR) in 49.6%, stable disease (SD) in 26.2% and progression disease (PD) in 17.7% patients. Patients were divided into two groups according to the result of neoadjuvant therapy--responders (CR+PR+SD, who successfully underwent surgery), and risk group (patients with SD or PD, who could not undergo surgery). Responders to neoadjuvant CHT/CHT+RT regimens reached statistically significant better EFS than non-responders, low tumor size (T2) and stage (II) categories were confirmed as additional predictive factors not only for EFS but for therapeutic response as well. The study primarily examined predictive power of tumor markers as CEA, Ca 15-3, and steroid receptors (ER/PR) and searched for their role in the prospective evaluation of neoadjuvant therapy. We evaluated these factors as potential predictors of EFS, independent in predictive power on therapeutic response to neoadjuvant therapy. Diagnostically valuable cut off points were proposed in ROC analysis for all these markers. Responders to the neoadjuvant therapy with Ca 15-3 <23.0 kU/l, CEA <5.0 mg/l, estrogen receptors (ER) >5.0 fmol/mg or both estrogen /progesterone receptors (ER/PR) positive had statistically significantly better EFS in comparison to patients with Ca 15-3 >23.0 kU/l, CEA >5.0 mg/l, ER <5.0 fmol/mg, or other cases than patients double positive in ER/PR. Marker Ca 15-3 revealed significant predictive power even within the group of non- responders, these patients with Ca 15-3 <23.0 kU/l had better EFS as compared to patients with Ca 15-3 >23.0 kU/l. Tumor size and low stage proved predictive value for immediate response to neoadjuvant therapy. Risk parameters for neoadjuvant therapy were T4, stage III, namely if RT was necessary. Therapeutic response to neoadjuvant therapy was independent on investigated molecular parameters, but there was strong predictive association of Ca 15-3, CEA and ER/PR receptors with event free survival development. Diagnostically valuable cut-off points were proposed and validated for sensitivity and specificity in ROC analysis.