Background:

The EndoPredict [EP] is a multi-gene expression assay designed to predict the replapse-free survival of patients with estrogen receptor [ER] positive, HER2 negative breast cancer treated with adjuvant endocrine therapy alone. Relative expression levels of the eight prognostic genes [AZGP1, BIRC5, DHCR7, IL6ST, MGP, RBBP8, STC2, UBE2C] and 3 reference genes were analyzed by real-time PCR system. EP low-risk patients have a better RFS when treated with endocrine therapy. One study indicated that EP high-risk patients are more sensitive to anathracycline-based neoadjuvant chemotherapy than low-risk patient.

Palbociclib is an orally active potent and highly selective reversible inhibitor of CDK4/6. N007 study aims to evaluate the efficacy of the pre-operative use of letrozole plus palbociclib for ER positive, HER2 negative post-menopausal breast cancer. Whether EP could predict for response and outcome to such treatment will be evaluated.

Method:

Twenty patients were treated. EP assays were intended to be tested for all patients. RNA were extracted from paired FFPE tumour blocks [core biopsies and corresponding surgical sections]. EP score were calculated for the first 7 paired samples. Also the EP Clin Score which integrate both mRNA of prognostic genes expression and their pathological parameters, including tumor size and nodal status, were also evaluated. The change in EP score were compared with that of Ki67 and also with the pathologic tumor response.

Results:

The results of the first 7 patients were presented. The overall pCR rate rate was 14.3%[1/7]. 85.7% [6/7] samples were classified as low risk group. Paired T-test showed EP score is significantly lower [P=0.0014] after neoadjuvant hormonal treatment [NHT]. The change of EP score before and after treatment corresponds to the change in Ki67. Both have a similar prediction of response. EP scores either remained high or showed minimal change for patients with stable disease [SD]. The subsequent EP Clin score was high for one of such patients, indicating high clinical risk. The corresponding Ki67 did not show any change and was low after treatment.

Results

Subject EP (before) EP (after) Ki67 (before) Ki67 (after) Change in EP Change in Ki67 EP CLin 
001 4.9 3.7 5% 1% -1.2 .4% 2.7 
002 8.2 4.7 50% 3% -3.5 .47% 2.3 
003 10 7.1 13% 13% -2.9 0% 4.3 
004 5.6 10% -5.6 -100% 
005 7.7 5.3 9% 1% -2.4 -8% 2.8 
006 3.7 2.2 20% 8% -1.5 -12% 2.6 
007 4.4 3.7 10% 5% -0.7 -5% 3.4 
Subject EP (before) EP (after) Ki67 (before) Ki67 (after) Change in EP Change in Ki67 EP CLin 
001 4.9 3.7 5% 1% -1.2 .4% 2.7 
002 8.2 4.7 50% 3% -3.5 .47% 2.3 
003 10 7.1 13% 13% -2.9 0% 4.3 
004 5.6 10% -5.6 -100% 
005 7.7 5.3 9% 1% -2.4 -8% 2.8 
006 3.7 2.2 20% 8% -1.5 -12% 2.6 
007 4.4 3.7 10% 5% -0.7 -5% 3.4 

Conclusion:

pCR has been used as an endpoint for neoadjuvant chemotherapy trial. Our data suggest that the EP score can be reliably determined in core biopsy specimens and can be applied as endpoint on NHT trials. Changes in EP score correlated with that of Ki67 and also with response. However, changes in EP score may have a better prediction of response than Ki67. EP Clin score, which integrates clinical parameters, may predict subsequent risk and clinical outcome after treatment. The data of all the 20 patients will be presented at the meeting.

Citation Format: Chow LWC, Toi M. EndoPredict multigene test in the prediction of response and outcome after neoadjuvant hormonal treatment with letrozole adn palbociclib (OOTR-N007) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-17.