Abstract
Abstract Purpose: Studies have shown that the 70-gene signature (MammaPrint®) (MP) may outperform clinicopathological risk assessment and may predict the benefit from chemotherapy (CT) in patients (pts) with early-stage breast cancer. However, the need of fresh tissue and the high cost of the assay limit its use in daily clinical practice. We investigated whether 1) tumor clinicopathologic features can predict MP risk (high vs. low); 2) MP results could help to make decisions for the use of CT in pts with ER positive (ER+ve) breast cancer beyond recommendations of known international guidelines (NCCN, St. Gallen). Patients and methods: Women with operable invasive breast cancer without evidence of distant disease undergoing surgery at the Breast Surgery Department were enrolled into the study. A 3 mm punch biopsy of the tumor was obtained from the specimen within the first hour after surgery. Samples were shipped to the laboratory in an RNA-stabilizing solution and were studied to ensure the presence of at least 30% of tumor cells and a customized microarray containing 70 genes was analyzed as described by the manufacturer. Results: 124 consecutive pts were enrolled into the study; 106 tumor samples were adequate for the microarray. Median age was 53 yrs (range 28–83), mean tumor size was 2.3 cm (SD ±1.34), 52.4% pts had pN0, 55% of tumors had Ki-67 ≥20% and 36% were poorly differentiated. ER were detected in ≥50% of cells in 82% and <1% of cells in 15% of tumors, respectively; HER2 was positive in 18% of tumors. As expected, poorly differentiated, ER and PgR negative, HER2 positive and highly proliferating tumors were more likely to be classified as high-MP. We then focused our analysis on ER and PgR +ve, HER2 negative tumors and assessed features correlated with MP results in this subgroup. Unexpectedly, 31/80 (39%) of these tumors were classified as high-MP vs. 49 (61%) low-MP. We found that tumor size (T1 vs. T2-T4), poor differentiation (G3 vs G1-2) and high proliferation (Ki-67 ≥20%) were significantly associated with a high-MP result. In an exploratory multivariate analysis tumor size and Ki-67 remained as independent predictors of high-MP result. At last, when we compared MP risk with recommendations for AT from international guidelines we found that in the subgroup of candidates for endocrine therapy (ET) in whom the benefit from the addition of CT is undetermined, 25/68 pts (37%) were high-MP and 43 pts (63%) low-MP. When we considered recommendations for AT proposed by our multidisciplinary team according to international guidelines, 11/25 pts (44%) with high-MP received ET only and 14 pts (56%) CT + ET, while among 43 pts with low-MP only 9 received both CT and ET. Conclusions: Our study shows that the 70-gene signature was feasible in the clinical setting, as 85% of tumor samples were adequate. A substantial proportion of ER/PgR+ve, HER2 negative tumors was classified as high-MP; within this subgroup, proliferation and tumor size independently predicted high-MP results. In 20 pts, MP risk would have resulted in discordant recommendations for AT compared to those based on standard clinicopathologic features. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-27.
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