Lani
01-24-2014, 01:56 AM
Research-Based PAM50 Subtype Predictor Identifies Higher Responses and Improved Survival Outcomes in HER2-Positive Breast Cancer in the NOAH Study
Aleix Prat (http://clincancerres.aacrjournals.org/search?author1=Aleix+Prat&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),2 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Giampaolo Bianchini (http://clincancerres.aacrjournals.org/search?author1=Giampaolo+Bianchini&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Marlene Thomas (http://clincancerres.aacrjournals.org/search?author1=Marlene+Thomas&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Anton Belousov (http://clincancerres.aacrjournals.org/search?author1=Anton+Belousov&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Maggie C.U. Cheang (http://clincancerres.aacrjournals.org/search?author1=Maggie+C.U.+Cheang&sortspec=date&submit=Submit)7 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Astrid Koehler (http://clincancerres.aacrjournals.org/search?author1=Astrid+Koehler&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Patricia Gómez (http://clincancerres.aacrjournals.org/search?author1=Patricia+G%C3%B3mez&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Vladimir Semiglazov (http://clincancerres.aacrjournals.org/search?author1=Vladimir+Semiglazov&sortspec=date&submit=Submit)8 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Wolfgang Eiermann (http://clincancerres.aacrjournals.org/search?author1=Wolfgang+Eiermann&sortspec=date&submit=Submit)6 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Sergei Tjulandin (http://clincancerres.aacrjournals.org/search?author1=Sergei+Tjulandin&sortspec=date&submit=Submit)9 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Mikhail Byakhow (http://clincancerres.aacrjournals.org/search?author1=Mikhail+Byakhow&sortspec=date&submit=Submit)10 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Begoña Bermejo (http://clincancerres.aacrjournals.org/search?author1=Bego%C3%B1a+Bermejo&sortspec=date&submit=Submit)3 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Milvia Zambetti (http://clincancerres.aacrjournals.org/search?author1=Milvia+Zambetti&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Federico Vazquez (http://clincancerres.aacrjournals.org/search?author1=Federico+Vazquez&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Luca Gianni (http://clincancerres.aacrjournals.org/search?author1=Luca+Gianni&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1), and
José Baselga (http://clincancerres.aacrjournals.org/search?author1=Jos%C3%A9+Baselga&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),11 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1)
+ (http://clincancerres.aacrjournals.org/content/20/2/511#) Author Affiliations
Authors' Affiliations: 1Translational Genomics Group, Vall d'Hebron Institute of Oncology; 2Department of Medicine, Universitat Autònoma de Barcelona, Barcelona; 3Hospital Clinico Universitario, Valencia, Spain; 4Oncologia Medica, San Raffaele Cancer Centre, Milan, Italy; 5Roche, Pharma Research and Early Development, Penzberg; 6Frauenklinik vom Roten Kreuz, Munich, Germany; 7University of North Carolina, Chapel Hill, North Carolina; 8NN Petrov Research Institute of Oncology, St Petersburg, Russian Federation; 9NN Blokhin Russian Cancer Centre; 10Central Clinical Hospital named after N A Semashko, Moscow, Russia; and 11Memorial Sloan-Kettering Cancer Center, New York, New York
Corresponding Author:
José Baselga, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Phone: 212-639-3201; Fax: 212-794-3182; E-mail: baselgaj@mskcc.org
Abstract
Purpose: We report a retrospective exploratory analysis of the association of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor with pathologic complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
Experimental Design: Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded core biopsies from 114 pretreated patients with HER2-positive (HER2+) tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in combination with trastuzumab for one year. A control cohort of 42 patients with HER2-negative tumors treated with AT-CMF was also included. The PAM50 subtypes, the PAM50 proliferation score, and the PAM50 risk of relapse score based on subtype (RORS) and subtype and proliferation (RORP) were evaluated.
Results: HER2-enriched (HER2-E) tumors predominated within HER2+ disease, although all PAM50 intrinsic subtypes were identified across the three cohorts. The OR for achieving pCR with trastuzumab-based chemotherapy for HER2+/HER2-E and HER2+/RORP-high were 5.117 (P = 0.009) and 8.469 (P = 0.025), respectively, compared with chemotherapy only. The pCR rates of HER2+/HER2-E and HER2+/RORP-high after trastuzumab-based chemotherapy were 52.9% and 75.0%, respectively. A statistically nonsignificant trend was observed for more pronounced survival benefit with trastuzumab in patients with HER2+/HER2-E and HER2+/RORP-high tumors compared with patients with HER2+/non-HER2-E and HER2+/non-RORP-high tumors, respectively.
Conclusions: As determined by EFS and pCR, patients with HER2+/HER2-E tumors, or HER2+/RORP-high tumors, benefit substantially from trastuzumab-based chemotherapy. The clinical value of this genomic test within HER2+ disease warrants further investigation. Clin Cancer Res; 20(2); 511–21. ©2014 AACR.
Footnotes
Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
Received January 25, 2013.
Revision received October 8, 2013.
Accepted October 9, 2013.
©2014 American Association for Cancer Research.
http://clincancerres.aacrjournals.org/shared/img/common/social-bookmarking/citeulike.gif (http://clincancerres.aacrjournals.org/external-ref?tag_url=http://clincancerres.aacrjournals.org/cgi/content/long/20/2/511&title=Research-Based%20PAM50%20Subtype%20Predictor%20Identifies%2 0Higher%20Responses%20and%20Improved%20Survival%20 Outcomes%20in%20HER2-Positive%20Breast%20Cancer%20in%20the%20NOAH%20Stu dy+--+Prat%20et%20al.%2020%20%282%29%3A%20511+--+&doi=10.1158/1078-0432.CCR-13-0239&link_type=CITEULIKE)
Aleix Prat (http://clincancerres.aacrjournals.org/search?author1=Aleix+Prat&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),2 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Giampaolo Bianchini (http://clincancerres.aacrjournals.org/search?author1=Giampaolo+Bianchini&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Marlene Thomas (http://clincancerres.aacrjournals.org/search?author1=Marlene+Thomas&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Anton Belousov (http://clincancerres.aacrjournals.org/search?author1=Anton+Belousov&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Maggie C.U. Cheang (http://clincancerres.aacrjournals.org/search?author1=Maggie+C.U.+Cheang&sortspec=date&submit=Submit)7 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Astrid Koehler (http://clincancerres.aacrjournals.org/search?author1=Astrid+Koehler&sortspec=date&submit=Submit)5 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Patricia Gómez (http://clincancerres.aacrjournals.org/search?author1=Patricia+G%C3%B3mez&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Vladimir Semiglazov (http://clincancerres.aacrjournals.org/search?author1=Vladimir+Semiglazov&sortspec=date&submit=Submit)8 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Wolfgang Eiermann (http://clincancerres.aacrjournals.org/search?author1=Wolfgang+Eiermann&sortspec=date&submit=Submit)6 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Sergei Tjulandin (http://clincancerres.aacrjournals.org/search?author1=Sergei+Tjulandin&sortspec=date&submit=Submit)9 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Mikhail Byakhow (http://clincancerres.aacrjournals.org/search?author1=Mikhail+Byakhow&sortspec=date&submit=Submit)10 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Begoña Bermejo (http://clincancerres.aacrjournals.org/search?author1=Bego%C3%B1a+Bermejo&sortspec=date&submit=Submit)3 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Milvia Zambetti (http://clincancerres.aacrjournals.org/search?author1=Milvia+Zambetti&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Federico Vazquez (http://clincancerres.aacrjournals.org/search?author1=Federico+Vazquez&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),
Luca Gianni (http://clincancerres.aacrjournals.org/search?author1=Luca+Gianni&sortspec=date&submit=Submit)4 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1), and
José Baselga (http://clincancerres.aacrjournals.org/search?author1=Jos%C3%A9+Baselga&sortspec=date&submit=Submit)1 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1),11 (http://clincancerres.aacrjournals.org/content/20/2/511#aff-1)
+ (http://clincancerres.aacrjournals.org/content/20/2/511#) Author Affiliations
Authors' Affiliations: 1Translational Genomics Group, Vall d'Hebron Institute of Oncology; 2Department of Medicine, Universitat Autònoma de Barcelona, Barcelona; 3Hospital Clinico Universitario, Valencia, Spain; 4Oncologia Medica, San Raffaele Cancer Centre, Milan, Italy; 5Roche, Pharma Research and Early Development, Penzberg; 6Frauenklinik vom Roten Kreuz, Munich, Germany; 7University of North Carolina, Chapel Hill, North Carolina; 8NN Petrov Research Institute of Oncology, St Petersburg, Russian Federation; 9NN Blokhin Russian Cancer Centre; 10Central Clinical Hospital named after N A Semashko, Moscow, Russia; and 11Memorial Sloan-Kettering Cancer Center, New York, New York
Corresponding Author:
José Baselga, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Phone: 212-639-3201; Fax: 212-794-3182; E-mail: baselgaj@mskcc.org
Abstract
Purpose: We report a retrospective exploratory analysis of the association of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor with pathologic complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
Experimental Design: Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded core biopsies from 114 pretreated patients with HER2-positive (HER2+) tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in combination with trastuzumab for one year. A control cohort of 42 patients with HER2-negative tumors treated with AT-CMF was also included. The PAM50 subtypes, the PAM50 proliferation score, and the PAM50 risk of relapse score based on subtype (RORS) and subtype and proliferation (RORP) were evaluated.
Results: HER2-enriched (HER2-E) tumors predominated within HER2+ disease, although all PAM50 intrinsic subtypes were identified across the three cohorts. The OR for achieving pCR with trastuzumab-based chemotherapy for HER2+/HER2-E and HER2+/RORP-high were 5.117 (P = 0.009) and 8.469 (P = 0.025), respectively, compared with chemotherapy only. The pCR rates of HER2+/HER2-E and HER2+/RORP-high after trastuzumab-based chemotherapy were 52.9% and 75.0%, respectively. A statistically nonsignificant trend was observed for more pronounced survival benefit with trastuzumab in patients with HER2+/HER2-E and HER2+/RORP-high tumors compared with patients with HER2+/non-HER2-E and HER2+/non-RORP-high tumors, respectively.
Conclusions: As determined by EFS and pCR, patients with HER2+/HER2-E tumors, or HER2+/RORP-high tumors, benefit substantially from trastuzumab-based chemotherapy. The clinical value of this genomic test within HER2+ disease warrants further investigation. Clin Cancer Res; 20(2); 511–21. ©2014 AACR.
Footnotes
Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
Received January 25, 2013.
Revision received October 8, 2013.
Accepted October 9, 2013.
©2014 American Association for Cancer Research.
http://clincancerres.aacrjournals.org/shared/img/common/social-bookmarking/citeulike.gif (http://clincancerres.aacrjournals.org/external-ref?tag_url=http://clincancerres.aacrjournals.org/cgi/content/long/20/2/511&title=Research-Based%20PAM50%20Subtype%20Predictor%20Identifies%2 0Higher%20Responses%20and%20Improved%20Survival%20 Outcomes%20in%20HER2-Positive%20Breast%20Cancer%20in%20the%20NOAH%20Stu dy+--+Prat%20et%20al.%2020%20%282%29%3A%20511+--+&doi=10.1158/1078-0432.CCR-13-0239&link_type=CITEULIKE)