The 70-gene prognosis profile predicts early metastases in postmenopausal breast cancer patients.
Authors: Mook S , Schmidt MK , Weigelt B , Kreike B , Eekhout I , Glas AM , Floore AN , Rutgers EJ , Van 't Veer LJ 
Published: December 2010

Abstract #1063

Introduction&#x2028; By using gene expression profiling, Van 't Veer and colleagues developed a 70-gene prognosis profile to identify breast cancer patients who are at low risk of developing distant metastases and therefore might be safely spared chemotherapy. This 70-gene profile has been developed using tumors from a selected group of patients, i.e. women under the age of 55 years at diagnosis with stage I or II tumors. However, the majority of breast cancer patients are older, postmenopausal women who are increasingly being offered adjuvant chemotherapy despite the more favorable biological characteristics of their tumors, such as a lower proliferation rate and a high endocrine sensitivity. The aim of this study was to evaluate the prognostic value of the 70-gene prognosis profile in postmenopausal women with node-negative breast cancer.&#x2028; Methods&#x2028; Frozen tumor samples from 148 node-negative, breast cancer patients aged between 55 and 70 years at diagnosis were selected. Patients were treated with breast conserving therapy or mastectomy with axillary lymph node dissection between 1984 and 1996 at the Netherlands Cancer Institute. Eighteen percent received adjuvant tamoxifen, none of the patients received adjuvant chemotherapy. Samples were evaluated by gene expression profiling for the 70-gene profile and were classified as genomic high risk or genomic low risk. Clinical risk was assessed using Adjuvant! Online. The median follow-up was 11.6 years.&#x2028; Results&#x2028; Among the 148 patients, 91 (61%) were classified as genomic low risk, whereas 57 (39%) were classified as genomic high risk. The breast cancer specific survival (BCSS) at 5 and 10 years were 99% (SE 0.01) and 90% (SE 0.04), respectively, for the genomic low risk group versus 80% (SE 0.05) and 69% (SE 0.06), respectively, for the genomic high risk group (log rank p=0.036). The 70-gene prognosis profile was a predictor for BCSS at 5 and 10 years with hazard ratios (HR) of 19.1 (95% CI 2.5-148; p=0.005) and 3.9 (95% CI 1.7-9.0; p=0.002), respectively. In a multivariate model for BCSS including the genomic risk classification by the 70-gene prognosis profile and the clinical risk assessment by Adjuvant! online the profile outperformed the clinical risk assessment with a HR of 14.4 (95% CI 1.7-122.2; p=0.01) for BCSS at 5 years. The adjusted HR for the 70-gene profile for BCSS at 10 years was 2.2 (0.9-5.5; p=0.08).&#x2028; Conclusion &#x2028; Our results show that the 70-gene prognosis profile is also a strong predictor of BCSS in postmenopausal women. In addition, the profile can accurately select patients at high risk of early metastases within 5 years of diagnosis. Since the beneficial effect of chemotherapy in older women predominantly occurs in the first 5 years, the profile can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1063.