Jean
02-24-2010, 01:12 PM
Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in Postmenopausal Women With Node-Positive, Oestrogen-Receptor-Positive Breast Cancer on Chemotherapy
Lancet Oncol. 2010 Jan 1;11(1):55-65, KS Albain, WE Barlow, S Shak, GN Hortobagyi, RB Livingston, I-T Yeh, P Ravdin, R Bugarini, FL Baehner, NE Davidson, GW Sledge, EP Winer, C Hudis, JN Ingle, EA Perez, KI Pritchard, L Shepherd, JR Gralow, C Yoshizawa, DC Allred, CK Osborne, DF Hayes, for The Breast Cancer Intergroup of North America
In women with node-positive breast cancer, a high recurrence score was prognostic of longer disease-free survival for those treated with tamoxifen and anthracycline-based chemotherapy. Women with a low...
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
In women with node-positive breast cancer, a high recurrence score was prognostic of longer disease-free survival for those treated with tamoxifen and anthracycline-based chemotherapy. Women with a low recurrence score received no benefit from anthracycline-based chemotherapy.
EXPERT COMMENTARY
Lee Schwartzberg, MD, Editor-in-Chief
Genomic profiling of node-negative, ER+ breast cancer using the 21-gene recurrence score is widely used to help establish prognosis with endocrine therapy and benefit of chemotherapy. This retrospective study demonstrates that the recurrence score retains its ability to predict response to anthracycline-based chemotherapy and prognosis after hormonal treatment in a lymph-node−positive population as well. The results have immediate practical implications as well as strengthening the argument that breast cancer is a continuum, with both biologic and clinical factors being important aspects for outcome.
ABSTRACT
Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogenreceptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. Methods: The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes.
Findings: There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0•006; hazard ratio [HR] 2•64, 95% CI 1•33–5•27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0•97; HR 1•02, 0•54–1•93), but an improvement in disease-free survival for those with a high recurrence score (score ≥31; log-rank p=0•033; HR 0•59, 0•35–1•01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0•029), with no additional prediction beyond 5 years (p=0•58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival.
Interpretation: The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes.
Funding: National Cancer Institute and Genomic Health.
Lancet Oncol. 2010 Jan 1;11(1):55-65, KS Albain, WE Barlow, S Shak, GN Hortobagyi, RB Livingston, I-T Yeh, P Ravdin, R Bugarini, FL Baehner, NE Davidson, GW Sledge, EP Winer, C Hudis, JN Ingle, EA Perez, KI Pritchard, L Shepherd, JR Gralow, C Yoshizawa, DC Allred, CK Osborne, DF Hayes, for The Breast Cancer Intergroup of North America
In women with node-positive breast cancer, a high recurrence score was prognostic of longer disease-free survival for those treated with tamoxifen and anthracycline-based chemotherapy. Women with a low...
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
In women with node-positive breast cancer, a high recurrence score was prognostic of longer disease-free survival for those treated with tamoxifen and anthracycline-based chemotherapy. Women with a low recurrence score received no benefit from anthracycline-based chemotherapy.
EXPERT COMMENTARY
Lee Schwartzberg, MD, Editor-in-Chief
Genomic profiling of node-negative, ER+ breast cancer using the 21-gene recurrence score is widely used to help establish prognosis with endocrine therapy and benefit of chemotherapy. This retrospective study demonstrates that the recurrence score retains its ability to predict response to anthracycline-based chemotherapy and prognosis after hormonal treatment in a lymph-node−positive population as well. The results have immediate practical implications as well as strengthening the argument that breast cancer is a continuum, with both biologic and clinical factors being important aspects for outcome.
ABSTRACT
Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogenreceptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. Methods: The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes.
Findings: There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0•006; hazard ratio [HR] 2•64, 95% CI 1•33–5•27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0•97; HR 1•02, 0•54–1•93), but an improvement in disease-free survival for those with a high recurrence score (score ≥31; log-rank p=0•033; HR 0•59, 0•35–1•01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0•029), with no additional prediction beyond 5 years (p=0•58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival.
Interpretation: The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes.
Funding: National Cancer Institute and Genomic Health.