Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome

Abstract

The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.

The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer

“…Bottini et al observed on multivariate analysis that clinical response, tumour size and PgR status were independent predictors for disease recurrence [15,20]. Faneyte and colleagues assessed the role of Ki67, ER, HER2, p53 and bcl2 in 97 women with breast cancer and extensive axillary node involvement and found none of these factors to be associated with DFS and OS [17]. The current findings have similarities to those we observed in patients treated with endocrine therapy.…”

“…In contrast, others have not found an independent relationship between post-neoadjuvant chemotherapy Ki67 and survival [14][15][16][17][18]. Three studies found ER status to be the sole independent predictor of DFS or RFS on multivariate analysis [14,16,19].…”

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

“…Most recently, several neoadjuvant trials suggest that ERα-tumors are more sensitive to chemotherapy than ERα+ tumors. [22][23][24][25][26][27] In addition, the world overview of adjuvant chemotherapy trials for breast cancer conducted by the Early Breast Cancer Collaborative Group supports the hypothesis that patients with ERα-breast cancer experience more benefit from adjuvant chemotherapy than patients with ERα+ disease. 28 The biological basis for the potential relationship between ERα and the effectiveness of adjuvant therapy remains uncertain, nonetheless differences in cell cycle regulation between ERα+ and ERα-tumors have, for a long time, been a central feature of most explanations that have been proffered.…”

Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy

“…The early identification of features associated with response or resistance to primary therapy are important in the development of the most effective multimodal approaches, and identifying cohorts of patients most likely to benefit from preoperative chemotherapy (PCT) [1][2][3]. Features predictive of response and outcome include steroid hormone receptor expression.…”