Abstract P5-08-31: Withdrawal of exogenous hormones affects prognostic multigene signature results in early luminal breast cancer
Authors: Jongen L , De Vries P , Van Asten K , Lintermans A , Laenen A , Wildiers H , Floris G , Neven P 
Published: May 2016

Background

Early breast cancer (BC) outcomes are mainly estimated based on clinicopathological parameters and rarely include proliferation markers: (Ki-67), and multigene signatures (MGS), which are typically measured in tumors from resection specimens (RS). We believe that tumor proliferation can change within days of anti-estrogen use. However, little is known how proliferation changes after withdrawal of hormone replacement therapy (HRT) or oral anti-conception (OAC) after a core needle biopsy (CNB) shows BC. Hence, this study compares the Ki-67 labeling index and the MGS results in CNB and RS collected from a cohort of patients under OAC/HRT.

Patients and Methods

This retrospective study included consecutive women diagnosed with a grade 1-2, any pTN0-1, primary operable estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and invasive ductal carcinoma between January 2013 and July 2014 at the Multidisciplinary Breast Center of University Hospitals Leuven were selected from a prospectively managed database. Ki-67 staining was performed on RS (Ki-67RS) to compare those who used HRT/OAC for at least 3 months at diagnosis and those not using OAC/HRT at diagnosis. OAC/HRT was always stopped between CNB and RS. Subsequently, we compared Ki-67 of the CNB (Ki-67CNB) with the matched RS in 15 patients with a low Ki-67RS (14%) stopping OAC/HRT after CNB; revised standard pathology confirmed absence of tumor heterogeneity in all samples. In addition, in a subset of patients (≥50 years, Ki-67RS ≤5%) we compared Ki-67 index and MGS results (MammaPrint (MP) and BluePrint, Agendia) from the CNB versus RS.

Results

193 patients with a known Ki-67RS were included; 38 patients (mean age of 55 years) were on OAC/HRT at CNB and 155 patients (mean age of 64 years) were not. The median time between stopping OAC/HRT and resection was 23 days (range 8-48 days). Ki-67RS was &lt;6%, 6-14% and ≥15% in 30.0%, 36.8% and 33.2% in the whole group of patients, respectively. These figures were 44.7%, 44.7% and 10.5% in patients on OAC/HRT at CNB diagnosis and 26.5%, 34.8% and 38.7% in patients not on OAC/HRT. This difference was significant (p&lt;0.05) for patients ≥50 years on HRT at CNB diagnosis. Four of 15 patients, which stopped OAC/HRT after the CNB (26.7%), showed a low Ki-67RS (≤14%) and had a high matched Ki-67CNB (≥15%). In another subset of four out of 15 patients we compared CNB and RS (table1) where we observed changes in both Ki-67 and MGS.

MP and Ki-67 results from matched CNB and RS. CNBRSPatientKi-67 (%)MP indexKi-67 (%)MP index150.371-20.31280.1150.043100.0650.03425-0.702-0.13Low risk is defined as MP index ≥0.0575 and/or Ki-67 ≤14.

Conclusion

Women on OAC/HRT, at diagnosis of an early luminal BC, are more likely to have a lower Ki-67RS as those not using OAC/HRT. Our findings are likely explained by a sudden decrease in sex steroids after BC diagnosis, resulting in lower proliferation markers. As such, a lower hormonal environment by withdrawing HRT/OAC at BC diagnosis might underestimate proliferation markers used for prognostic and predictive purposes. Therefore we are currently testing this hypothesis in larger cohorts.

Citation Format: Jongen L, De Vries P, Van Asten K, Lintermans A, Laenen A, Wildiers H, Floris G, Neven P. Withdrawal of exogenous hormones affects prognostic multigene signature results in early luminal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-31.