BACKGROUND: Breast cancer is a leading cause of morbidity and mortality in women worldwide. About 70 % of breast cancers are estrogen receptor (ER) positive. Blocking estrogen action by tamoxifen has been the treatment of choice in ER positive breast cancers for more than 30 years. In the past, several studies have revealed associations between gene copy number alterations and responsiveness to tamoxifen therapy, but so far no single gene copy number alteration could completely explain the response variation observed between individual breast cancer patients. Here, we set out to perform a simultaneous analysis of copy number alterations of several genes involved in the prognosis and response to therapy by multiplex ligation-dependent probe amplification (MLPA). METHODS: A case-control study was designed encompassing 170 non-metastatic ER positive breast cancer patients (case group = 85, control group = 85). All patients in the control group had received standard adjuvant tamoxifen treatment for 5 years without any evidence of recurrence. Patients in the case group had experienced early recurrences while receiving tamoxifen treatment. 76 % of the patients of the case group and 73 % of the patients of the control group had received anthracycline-based adjuvant chemotherapy. Gene copy number alterations detected by MLPA in both groups were compared. RESULTS: Amplification of CCND1 (OR = 3.13; 95 % CI = 1.35 to 7.26; p = 0.006) and TOP2A (OR = 3.05; 95 % CI = 1.13 to 8.24; p = 0.022) were significantly more prevalent in the case group, compared to the control group. In a multivariate analysis CCND1 (p = 0.01) and TOP2A (p = 0.041) amplifications remained significant predictors of recurrence. CONCLUSIONS: Our results indicate that CCND1 amplification may serve as a useful biomarker for hormone responsiveness, and that TOP2A amplification may serve as a useful prognostic biomarker.
BACKGROUND:Breast cancer is a leading cause of morbidity and mortality in women worldwide. About 70 % of breast cancers are estrogen receptor (ER) positive. Blocking estrogen action by tamoxifen has been the treatment of choice in ER positive breast cancers for more than 30 years. In the past, several studies have revealed associations between gene copy number alterations and responsiveness to tamoxifen therapy, but so far no single gene copy number alteration could completely explain the response variation observed between individual breast cancerpatients. Here, we set out to perform a simultaneous analysis of copy number alterations of several genes involved in the prognosis and response to therapy by multiplex ligation-dependent probe amplification (MLPA). METHODS: A case-control study was designed encompassing 170 non-metastatic ER positive breast cancerpatients (case group = 85, control group = 85). All patients in the control group had received standard adjuvant tamoxifen treatment for 5 years without any evidence of recurrence. Patients in the case group had experienced early recurrences while receiving tamoxifen treatment. 76 % of the patients of the case group and 73 % of the patients of the control group had received anthracycline-based adjuvant chemotherapy. Gene copy number alterations detected by MLPA in both groups were compared. RESULTS: Amplification of CCND1 (OR = 3.13; 95 % CI = 1.35 to 7.26; p = 0.006) and TOP2A (OR = 3.05; 95 % CI = 1.13 to 8.24; p = 0.022) were significantly more prevalent in the case group, compared to the control group. In a multivariate analysis CCND1 (p = 0.01) and TOP2A (p = 0.041) amplifications remained significant predictors of recurrence. CONCLUSIONS: Our results indicate that CCND1 amplification may serve as a useful biomarker for hormone responsiveness, and that TOP2A amplification may serve as a useful prognostic biomarker.
Authors: Kirsten Vang Nielsen; Bent Ejlertsen; Sven Müller; Susanne Møller; Birgitte B Rasmussen; Eva Balslev; Anne-Vibeke Lænkholm; Peer Christiansen; Henning T Mouridsen Journal: Breast Cancer Res Treat Date: 2010-06-17 Impact factor: 4.872
Authors: D A Berry; H B Muss; A D Thor; L Dressler; E T Liu; G Broadwater; D R Budman; I C Henderson; M Barcos; D Hayes; L Norton Journal: J Clin Oncol Date: 2000-10-15 Impact factor: 44.544
Authors: Ann S Knoop; Helle Knudsen; Eva Balslev; Birgitte B Rasmussen; Jens Overgaard; Kirsten V Nielsen; Andreas Schonau; Katrín Gunnarsdóttir; Karen E Olsen; Henning Mouridsen; Bent Ejlertsen Journal: J Clin Oncol Date: 2005-10-20 Impact factor: 44.544
Authors: Somaia Elsheikh; Andrew R Green; Mohammed A Aleskandarany; Matthew Grainge; Claire E Paish; Maryou B K Lambros; Jorge S Reis-Filho; Ian O Ellis Journal: Breast Cancer Res Treat Date: 2007-07-26 Impact factor: 4.872
Authors: Miangela M Lacle; Cathy B Moelans; Robert Kornegoor; Carmen van der Pol; Arjen J Witkamp; Elsken van der Wall; Josef Rueschoff; Horst Buerger; Paul J van Diest Journal: Cell Oncol (Dordr) Date: 2015-04-24 Impact factor: 6.730