Abstract P4-08-08: Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study
Authors: Gil-Gil M , Morilla I , Petit A , Soler T , Perez-Martin X , Guma A , Pla MJ , Ortega R , Garcia-Tejedor A , Falo C , Montal R , Perez-Casanova L , Loayza C , Pernas S 
Published: February 2018

Background:

Neoadjuvant endocrine therapy (NET) is gaining more acceptances for the management of estrogen receptor (ER) positive breast cancer (BC). Rate of patients achieving pathological complete response is very low and Ki67 suppression and PEPI score are the only prognostic factors associated with relapse free survival.

The aim of our study was to identify biomarkers of prediction of distant relapse risk that could help clinicians in the decision-making of systemic adjuvant treatment in patients previously treated with NET

Material & Methods:

Retrospective study of 119 postmenopausal women with ER or progesterone receptor (PR) positive BC treated with NET in ICO-HUB from 1997 to 2009. Clinical-pathological data and treatments administered were reviewed. IHC expression of ER, PR, Ki67, Androgen receptor (AR), BCL-2, Cyclin D1 (CD1), p16, p53, CD 44 and synaptophysin were analyzed in post-NET surgical formalin-fixed paraffin-embedded tumor samples through a tissue microarray. Survival was calculated by Kaplan-Meier method. Univariate and multivariate analysis of variables associated with distant relapse free survival (DRFS) was evaluated by Cox proportional hazard model.

Results:

Mean age was 74 (63-88). cT: T2 5%, T3 6.5%, T4 43.5%. cN: N0 59%, N1 25%, N2-3 16%. Stage: I 21%, II 49.5%, III 29.5%. Histological subtype: ductal 84%, lobular 6%, others 10%. Histological grade: G1 20%, G2 55%, G3 25%.

Vascular invasion 15%. NET: Aromatase Inhibitors 64%, SERM 36%. Median duration of NET 8.5 months. Clinical Response: Complete 4%, Partial 55%, Stable 37%, Progression 4%. Surgery: Lumpectomy 72%, Mastectomy 28%;Lymphadenectomy 70.5%, Sentinel lymph node biopsy 6%, No surgical approach of axilla 23.5%. Surgical specimen: ypT1 36%, ypT2 54%, ypT3 6%, ypT4 4%; ypN0 28%, ypN1 22%, ypN2 13.5%, ypN3 12% ypNx 23.5%. Surgical margins: Negative 89% Positive 11%. Median fibrosis rate 20% (0-95). PR and Ki67 showed a statistically significant decrease after NET(p&lt;0,05) but no ER (p=0,29).

Adjuvant treatment: chemotherapy 7%, radiotherapy 76%, endocrine therapy 96%. Median follow-up: 104 months. Only 21 patients developed distance relapse. Median OS was 139 months [95% CI = 98-181]. Univariate analysis for DRFS showed statistically significant differences in cN (HR=3), histological grade 3 (HR=3.61), ypN (HR=3.62), p16 (HR=6.1) and p53 (HR=2.79). Multivariate analysis of post-NET biomarkers showed that negative nuclear p16 expression (HR=4.79)and positive p53 (HR=2.83)were independently associated with worse DRFS. In multivariate analysis of all clinico-pathological and molecular factors, histological grade 3 (HR=2.82) was the sole DRFS independent factor.

Conclusions:

Negative nuclear p16 expression and positive p53 post-NET were associated with worseDRFS. Whenall clinico-pathological and molecular factors were analysed, G3 was the sole DRFS independent factor. Patients with G3, negative p16 or positive p53 after NET could probably benefit from adjuvant chemotherapy or CDK 4-6 inhibitors treatment. In our series, we did not find usefulness in analysing ER, PR and Ki67 post-NET changes to predict DRFS.

Citation Format: Gil-Gil M, Morilla I, Petit A, Soler T, Perez-Martin X, Guma A, Pla MJ, Ortega R, Garcia-Tejedor A, Falo C, Montal R, Perez-Casanova L, Loayza C, Pernas S. Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-08.