Cytosol protein content and prognosis in operable breast cancer

Summary Several biochemical parameters quantitated in tumor cytosols from malignant breast tumors have been evaluated as possible prognostic factors. Cytosol protein content has always been regarded as a reference parameter, to correct for cellularity and representativity of tumor samples. But recent studies have suggested an altered protein distribution in malignant tissues. The present study on 382 women with histologically proven breast cancer, Stage I and Stage II, therefore evaluates whether cytosol protein content by itself may add information as a prognostic factor in the clinical management of breast cancer.Cytosol protein content was found to be significantly correlated (p<0.001) to tumor size, and inversely correlated to progesterone receptor (PgR) content (p=0.015) and age at operation (p=0.021). Using the median value of protein (4.15 mg/ml) as a cut-off value, two groups could be constructed. The number of node-positive patients in the protein-poor group was significantly decreased (p=0.018) compared to the protein-rich group, which also contained a significantly (p<0.001) lower number of patients with estrogen receptor (ER) positive tumors (i.e. ER10 pmol/g). An increased number of events was observed in the protein-rich group (p<0.001), with a great contribution to the number of deaths due to breast cancer. In a multivariate analysis of the likelihood to predict axillary nodal involvement, protein category was found to be a significant (p<0.031) independent predictive factor. As to relapse free survival (RFS), protein category did not reveal any prognostic power. A subgroup containing Stage II patients with ER+ tumors was included in a prospective, randomized study on the role of tamoxifen as an adjuvant endocrine therapy. In a multivariate analysis, treatment option (tamoxifen vs. control) (p=0.0008) and axillary nodal tumor burden (p=0.009) were significant independent prognostic factors for RFS in protein-rich patients. In protein-poor patients, only tumor size showed a positive association with RFS, but without reaching statistical significance (p=0.062).The present observations make cytosol protein content interesting in the context of tumor biology and breast cancer prognosis. Further studies are needed to evaluate cytosol protein content as a possible prognostic factor useful in the clinical management of breast cancer.