70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_D8474667A7D5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
Journal
The New England journal of medicine
Working group(s)
MINDACT Investigators
Contributor(s)
Benn K., Bogaerts J., Cardoso F., Ciruelos E., Corochan S., Cuny J., de la Pena L., Delaloge S., DeLorenzi M., Dudek-Peric A., Eekhout I., Gluz O., Golfinopoulos V., Goulioti T., Harbeck N., Hilal V., Knox S., Lemonnier J., Ławniczak M., Marini L., Matos E., Morales P., Murray K., Nitz U., Passalaqua R., Piccart M., Remmelzwaal J., Rubio I., Rutgers E., Saghatchian M., Slaets L., Sotiriou C., Straehle C., Straley M., Theron N., Thompson A., Tryfonidis K., Todeschini R., Urunkar M., van 't Veer L., Viale G., Aalders K., Bines J., Bedard P., Bozovic I., Braga S., Castaneda C., Celebic A., Colichi C., Criscitiello C., Dal Lago L., Demonty G., Drukker C., Fei F., Lia M., Loi S., Messina C., Mook S., Moulin C., Sreseli R., Therasse P., Werutsky G., Corachan S., Dudek-Peric A., Wheeler L., Dif N., Rizzetto G., Beauvois M., Meirsman L., Breyssens H., Decker N., Engelen K., Akropovic A., Harrison J., Henot F., Celis M., De Jongh B., Delmotte I., Daubie V., Goossens R., Helsen N., Hourt L., Janssen S., Soete V., Vansevenant K., Hermans C., Hart G., Brink G., Floore A., Sixt B., Buyse M.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
25/08/2016
Peer-reviewed
Oui
Volume
375
Number
8
Pages
717-729
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy.
In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.
A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.
Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).
In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.
A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.
Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).
Keywords
Adult, Aged, Antineoplastic Agents/therapeutic use, Breast Neoplasms/drug therapy, Breast Neoplasms/genetics, Breast Neoplasms/mortality, Breast Neoplasms/surgery, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Gene Expression, Gene Expression Profiling, Genetic Predisposition to Disease, Genetic Testing, Humans, Kaplan-Meier Estimate, Mastectomy, Middle Aged, Neoplasm Metastasis/prevention & control, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Prospective Studies, Risk, Risk Assessment
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Web of science
Create date
27/10/2017 15:19
Last modification date
20/08/2019 16:57
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