PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.
RCT Entities:
PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.
Authors: John M S Bartlett; Cassandra L Brookes; Tammy Robson; Cornelis J H van de Velde; Lucinda J Billingham; Fiona M Campbell; Margaret Grant; Annette Hasenburg; Elysée T M Hille; Charlene Kay; Dirk G Kieback; Hein Putter; Christos Markopoulos; Elma Meershoek-Klein Kranenbarg; Elizabeth A Mallon; Luc Dirix; Caroline Seynaeve; Daniel Rea Journal: J Clin Oncol Date: 2011-03-21 Impact factor: 44.544
Authors: Zaida Garcia-Casado; Angel Guerrero-Zotano; Antonio Llombart-Cussac; Ana Calatrava; Antonio Fernandez-Serra; Amparo Ruiz-Simon; Joaquin Gavila; Miguel A Climent; Sergio Almenar; Jose Cervera-Deval; Josefina Campos; Carlos Vazquez Albaladejo; Antonio Llombart-Bosch; Vicente Guillem; Jose A Lopez-Guerrero Journal: BMC Cancer Date: 2010-02-09 Impact factor: 4.430
Authors: A H Evans; S Pancholi; I Farmer; A Thornhill; D B Evans; S R Johnston; M Dowsett; L-A Martin Journal: Br J Cancer Date: 2010-04-13 Impact factor: 7.640