PURPOSE: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. EXPERIMENTAL DESIGN: One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP. RESULTS: The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016). CONCLUSION: Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.
PURPOSE: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. EXPERIMENTAL DESIGN: One hundred and ten operable breast cancerpatients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP. RESULTS: The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016). CONCLUSION: Our study indicates that breast cancerpatients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancerpatients to anthracycline-based neoadjuvant chemotherapy in clinical setting.
Authors: Sara Cattelani; Giovanna Ferrari-Amorotti; Sara Galavotti; Raffaella Defferrari; Barbara Tanno; Samantha Cialfi; Jenny Vergalli; Valentina Fragliasso; Clara Guerzoni; Gloria Manzotti; Angela Rachele Soliera; Chiara Menin; Roberta Bertorelle; Heather P McDowell; Alessandro Inserra; Maria Luisa Belli; Luigi Varesio; Deborah Tweddle; Gian Paolo Tonini; Pierluigi Altavista; Carlo Dominici; Giuseppe Raschellà; Bruno Calabretta Journal: Neoplasia Date: 2012-07 Impact factor: 5.715
Authors: Marjanka K Schmidt; Johanna Tommiska; Annegien Broeks; Flora E van Leeuwen; Laura J Van't Veer; Paul D P Pharoah; Douglas F Easton; Mitul Shah; Manjeet Humphreys; Thilo Dörk; Scarlett A Reincke; Rainer Fagerholm; Carl Blomqvist; Heli Nevanlinna Journal: Breast Cancer Res Date: 2009-12-18 Impact factor: 6.466