The Lancet. Oncology 2010-01
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.
Abstract
Background
The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-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 > or =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.
Related Questions
For ER+ breast cancers that are clinical Stage IIB (T2N1) nearing locally advanced stages, what criteria do you use to determine if you would offer neoadjuvant chemotherapy?
This is an interesting question. Assuming this is regarding ER positive but HER2 negative tumors, the factors I would consider that would favor the decision to use upfront chemotherapy are the following: 1. Tumors that are grade 3 or high Ki-67 2. Low ER positive tumors 3. Younger, premenopausal wom...
Can Oncotype be used in women with ER positive, 1-3 lymph node positive disease with extracapsular extension?
The use of Oncotype assay in 1-3 node positive women is addressed in RxPonder trial in which women with 1-3 positive nodes and oncotype scores of 25 or less were randomized to receive either endocrine versus chemoendocrine. The trial is fully enrolled but the results have been reported as yet. Howe...
Do you routinely send Oncotype Dx on ER positive tumors with node positive disease?
I believe that the intrinsic biology of the tumor is more important than the lymph node status in determining prognosis and potential chemotherapy benefit. Given this, I do use molecular assays for node positive disease with caution. Based on a 2010 Lancet Oncology paper in which tissue blocks from ...
In a patient with ER+/HER2- breast cancer, do you ever use Oncotype testing to assist in decision-making regarding adjuvant chemotherapy when the tumor size is less than 0.5 cm, or when there are positive lymph nodes?
The NSABP and other data that was approved for prognostication and for prediction of benefit with chemo excluded 5 mm or smaller tumors. In practice, oncologists would not offer chemo for ER positive and node negative tumors that are 5 mm or less in size . Thus, I would not do oncotype do testing. B...