Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

HER2 And Choice Of Adjuvant Chemotherapy For Invasive Breast Cancer: National Surgical Adjuvant Breast And Bowel Project Protocol B-15.

S. Paik, J. Bryant, E. Tan-chiu, G. Yothers, C. Park, D. L. Wickerham, N. Wolmark
Published 2000 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
BACKGROUND Recent retrospective analyses have suggested that breast cancer patients whose tumors overexpress HER2 derive preferential benefit from treatment with anthracyclines such as doxorubicin. This has led some clinicians to propose that HER2 should be used as a predictive marker in choosing between anthracycline-based regimens and combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). We evaluated this recommendation in a retrospective study of National Surgical Adjuvant Breast and Bowel Project Protocol B-15, in which patients received a combination of doxorubicin and cyclophosphamide (AC), CMF, or AC followed by CMF. We hypothesized that AC would be superior to CMF only in the HER2-positive patients. METHODS Immunohistochemical detection of HER2 was performed on tumor sections from 2034 of 2295 eligible patients. We used statistical analysis to evaluate the interaction between the efficacy of the assigned treatments and HER2 overexpression. All statistical tests were two-sided. RESULTS Tumor sections from 599 patients (29%) stained positive for HER2. AC was superior to CMF in HER2-positive patients only, although differences in outcomes did not reach statistical significance. In the HER2-positive cohort, relative risks of failure (i.e., after AC treatment as compared with CMF treatment) were 0.84 for disease-free survival (DFS) (95% confidence interval [CI] = 0.65--1.07; P =.15), 0.82 for survival (95% CI = 0.63--1.06; P =.14), and 0.80 for recurrence-free survival (RFS) (95% CI = 0.62--1.04; P =.10). Tests for interaction between treatment and HER2 status were suggestive but not statistically significant (P =.19 for DFS, P =.11 for survival, and P =.08 for RFS). CONCLUSIONS These results, together with overview results indicating minor overall superiority for anthracycline-based regimens relative to CMF, indicate a preference for the AC regimen in patients with HER2-positive tumors. Both AC and CMF regimens may be considered for patients with HER2-negative tumors.
This paper references
Benefits of CMF treatment in lymph node-positive breast cancer overexpressing HER2
S Menard (1999)
Polychemotherapy for early breast cancer: An overview of the randomised trials
O. Abe (1998)
10.1200/JCO.1992.10.7.1049
Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.
B. Gusterson (1992)
10.1016/S0140-6736(98)03301-7
Polychemotherapy for early breast cancer: an overview of the randomised trials
Early Breast Cancer Trialists' Collaborative Group (1998)
breast cancer be based on erbB-2 status? [editorial
PM Ravdin (1999)
10.1093/JNCI/90.18.1320
Should selection of adjuvant chemotherapy for patients with breast cancer be based on erbB-2 status?
G. Clark (1998)
10.1093/JNCI/91.2.110
Using HER2 to choose chemotherapy in breast cancer: is it ready for the clinic?
C. McNeil (1999)
10.1200/JCO.1990.8.9.1483
Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowe
B. Fisher (1990)
Should HER2 status be routinely measured for all breast cancer patients?
P. Ravdin (1999)
10.1056/NEJM199405053301802
c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.
H. Muss (1994)
10.1002/(SICI)1097-0215(19990820)84:4<354::AID-IJC4>3.0.CO;2-6
Effect of c‐erbB2 and estrogen receptor status on survival of women with primary breast cancer treated with adjuvant cyclophosphamide/methotrexate/fluorouracil
D. Miles (1999)
10.1093/JNCI/90.18.1346
erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer.
A. Thor (1998)
ready for the clinic? [news
S Paik (1998)
10.1093/JNCI/90.18.1361
erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.
S. Paik (1998)
Project ChemoInsight reveals physician practice patterns for adjuvant breast cancer chemotherapy, and compares the dose intensity of CMF, AC, and CAF [abstract
GA Smith (1999)
c - erbB2 expression and response to adjuvant therapy in women with node - positive early breast cancer [ published erratum appears in N Engl J Med 1994 ; 331 : 211 ]
AD Thor (1994)
Polychemotherapy for early breast cancer: an overview of the randomised trials
M. Clarke (1998)



This paper is referenced by
HER-2 / neu Expression in Resectable Gastric Cancer and its Relationship with Histopathologic Subtype , Grade , and Stage * 1
H. Raziee (2007)
10.1007/s10549-007-9656-y
HER2/neu in systemic therapy for women with breast cancer: a systematic review
B. Dhesy-Thind (2007)
10.1111/j.1365-2559.2007.02896.x
Predictive markers in breast cancer – the future
D. Faratian (2008)
10.1200/JCO.2005.04.0576
Breast cancer-specific mRNA transcripts presence in peripheral blood after adjuvant chemotherapy predicts poor survival among high-risk breast cancer patients treated with high-dose chemotherapy with peripheral blood stem cell support.
M. Quintela-Fandino (2006)
10.1002/gcc.20008
Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples
Rosemary E Mueller (2004)
The Use of Verbs in Research Articles : Corpus Analysis for Scientific Writing and Translation
A. Reimerink (2007)
Current Status of Cell Culture Drug Resistance Testing ( CCDRT ) May , 2002
L. Weisenthal (2005)
10.4066/BIOMEDICALRESEARCH.30-17-2421
SHP-1 reverses trastuzumab resistance and migration in HER2-positive breast cancer cells through the stat3/p-stat3 pathway
De-xin Lei (2018)
Prädiktiver Wert und Verlaufsbeobachtung der Tumorvaskularisierung in der primär systemischen Therapie des Mammakarzinoms
Ä. Direktor (2011)
Topoiia and Her-2/neu Overexpression/amplification in Barrett's Oesophagus, Dysplasia and Adenocarcinoma Topoiia and Her-2/neu Overexpression/amplification in Barrett's Oesophagus, Dysplasia and Adenocarcinoma
Elisa Rossi ()
10.1007/978-3-540-28266-2_16
Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Resistant Breast Cancer
A. Hamilton (2006)
Invasive Breast CancerPractice Guidelines in Oncology
M. Smith (2011)
10.1007/s00129-002-1193-5
Genetische Risikofaktoren des Mammakarzinoms
M. Beckmann (2002)
10.1200/JCO.2006.06.9054
Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials.
A. Taghian (2006)
10.1186/bcr1002
Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women
K. Pritchard (2005)
Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments.
J. Albanell (2001)
10.1177/000313481007600631
Analysis of Demographic and Tumor Characteristics of an Inner City Breast Cancer Patient Population Compared with Patients Treated in National Surgical Adjuvant Breast and Bowel Project Trials
A. J. Colfry (2010)
10.1093/JNCI/93.13.979
National Institutes of Health Consensus Development Conference statement: adjuvant therapy for breast cancer, November 1-3, 2000.
P. Eifel (2001)
10.1016/J.SEMCANCER.2005.04.007
Cyclin E as a prognostic and predictive marker in breast cancer.
K. Hunt (2005)
10.1007/BF03256317
Genomic Predictors of Outcome and Treatment Response in Breast Cancer
L. Dunn (2012)
10.1016/j.breast.2017.06.041
De-escalating and escalating systemic therapy in triple negative breast cancer.
L. Carey (2017)
HER-2-targeted therapy: lessons learned and future directions.
R. Nahta (2003)
10.1007/s00280-009-1208-1
Progression and treatment of HER2-positive breast cancer
April Davoli (2009)
10.1200/JCO.2002.08.125
Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.
C. V. Van Poznak (2002)
JNCCN HER 2 Testing in Breast Cancer : NCCN Task Force Report and Recommendations
R. Carlson (2006)
ORIGINAL ARTICLE
Li Jue (2001)
10.1093/ANNONC/MDI059
Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate.
M. Fornier (2005)
10.3389/fonc.2012.00062
Trastuzumab: Updated Mechanisms of Action and Resistance in Breast Cancer
Thụy Vũ (2012)
10.4103/0971-5851.99748
Guidelines for locoregional therapy in primary breast cancer in developing countries: The results of an expert panel at the 8th Annual Women's Cancer Initiative – Tata Memorial Hospital (WCI-TMH) Conference
A. Munshi (2012)
10.4414/SMW.2007.11899
The acute effect of trastuzumab infusion on ECG parameters in metastatic breast cancer patients.
Ozlem Yavas (2007)
10.1634/theoncologist.2008-0230
The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine.
J. Ross (2009)
10.1097/01.MP.0000038462.62634.B1
The Role of HER2/neu Overexpression/Amplification in the Progression of Ductal Carcinoma In Situ to Invasive Carcinoma of the Breast
E. Latta (2002)
See more
Semantic Scholar Logo Some data provided by SemanticScholar