Prognostic Value Of Androgen Receptor Expression Research Articles

Abstract PO2-08-02: Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy

Abstract Background Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. Methods We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. Results The positive rates of AR expression in HR +/HER2-, HR +/HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR +/HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR +/HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. Conclusions AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR +/HER2- subtype and in HR +/HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P= 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR +/HER2- and HR +/HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis Citation Format: Jin Zhang. Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-02.

Abstract PO5-03-10: The prognostic role of androgen receptor status in patients with triple negative breast cancer with an associated ductal carcinoma in situ

Abstract Abstract Background Triple negative breast cancer (TNBC) is defined by the lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Prognostic immunohistochemical biomarkers in TNBC have been studied in recent years such as the androgen receptor (AR) which is expressed in 10-40% of TNBC. However the prognostic value of AR expression is not clear. Here, we studied the prognostic significance of AR expression in combination with the presence of a ductal carcinoma in situ (DCIS). Considering DCIS is a precursor of invasive ductal carcinoma, we hypothesize that TNBC with co-existing DCIS and presence of AR expression is less aggressive and patients are older at diagnosis. Methods We analyzed data retrospectively from all patients with stage 1-3 TNBC who underwent primary surgery and adjuvant chemotherapy in the University hospitals Leuven, between 01-01-2000 and 31-12-2017. Patient and tumor related characteristics were compared between two subgroups, one with co-existing DCIS and one with pure invasive carcinoma, without co-existing DCIS. AR expression was assessed by immunohistochemistry (IHC). We used AR expression in ≥1% and ≥10% of cells as cut-off scores. The prognostic role of the expression of AR in combination with a co-existing DCIS was analyzed, using the distant metastasis rate as primary endpoint. Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Secondary endpoints were associations of AR expression with clinical-pathological characteristics, time between diagnosis and metastasis, and disease specific mortality. Results In the 426 included patients with TNBC, co-existing DCIS was present in 66.7%; AR expression was expressed ≥1% in 29.3% and ≥10% in 21.4% of cases. Median age at diagnosis was 51 years (range: 22-85y). Age at diagnosis was independent of DCIS, dependent of AR expression; in DCIS positive cases, median age was 49 years if AR negative (IHC < 1%), 53 years if AR positive (IHC ≥1%), and 56 years if AR positive (IHC ≥10%) (p=0.006). In contrast in DCIS negative cases, median age was 51 years if AR negative (IHC < 1%), 51 if AR positive (IHC ≥1%), and 51 years if AR positive (IHC ≥10%) (p=0.895). AR expression was DCIS dependent and was ≥1% in 34.9% and ≥10% in 25.0% of patients in the DCIS group compared to 18.3% and 14.1% in the non-DCIS group (p=0.001 and p< 0.001 respectively). In both subgroups there was no significant difference for AR positive versus AR negative cases in lymph node involvement, tumor grade, tumor size and Nottingham Prognostic Index. Patients with a coexisting DCIS and AR expression did not have a different incidence of distant relapse compared to AR negative cases (AR ≥1%: p=0.2803 and AR ≥10%: p=0.5527). Of patients with coexisting DCIS, 12.0% (95% CI: 7.8; 17.1) in the AR negative group, 8.2% (95% CI: 3.8; 14.6) in the AR ≥ 1% group and 7.1% (95% CI: 2.6; 14.7) in the AR ≥ 10% group, had distant relapse within 2 years. Conclusion In patients with TNBC, AR expression is associated with older age in case of co-existing DCIS and patients with co-existing DCIS are more frequently AR positive. In patients with co-existing DCIS, there was no significant difference in distant relapse between AR negative and AR positive cases. Citation Format: Micaëlle Merckx. The prognostic role of androgen receptor status in patients with triple negative breast cancer with an associated ductal carcinoma in situ [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-10.

Abstract 4362: Combination of conventional therapies and antiandrogenic treatments as a succesful tool for triple negative breast cancer (TNBC) treatment

Abstract Triple negative breast cancer (TNBC) patients do not benefit from conventional hormonal therapies due to the loss of expression of ER, PR, and HER2. Therefore, the usual adjuvant treatments for breast cancer, are not applied to TNBC. Recently, it has been found that approximately one third of TNBC tumours express androgen receptor (AR) and it is associated with better response to endocrine therapies. However, the prognostic value of AR expression in TNBC is still unclear. Therefore, in this preliminary study we evaluate the effectiveness of an anti-androgen treatment (bicalutamide) respect to conventional treatments (doxorubicin and lapatinib) in TNBC human cell lines and their corresponding xenografts. Briefly, SUM149, SUM159 and MDAMB231 TNBC cell lines were cultured in supplemented medium. Cells were plated in 96-well plates and a serial dilution of Doxorubicin, Lapatinib, Bicatulamide and respective combinations were added. In addition, 106 cells were implanted subcutaneosly into five female mice (Balb/C SCID). When tumors developed, mice were treated with doxorubicin, bicalutamide, doxorubicin + bicalutamide and doxorubicin + bicalutamide + lapatinib. Every treatment was perfomed every 3 days during 15 days and tumor reduction and appearance of metastases were evaluated. Results from cell culture showed that neoplasic cells from each cell line were high sensitive to bicalutamide treatment (SUM149 EC50: 9,860e009; MDAMB231 EC50: 9,454e009; SUM159 EC50: 2,170e009). Also, viability decreased when we added an anti-androgen (bicalutamide) to the conventional treatments (doxorubicin + lapatinib). In vivo experiments revealed a greater percentage of tumour reduction (around 70%) in mice treated with combination of treatments and a lower appearance of metastasis was observed in this group respect to control group (SUM149: 40% vs 60%; MDA-MB-231: 20% vs 75%; SUM159: 20% vs 60%). Therefore, our preliminary findings suggest that the addition of an anti-androgenic agent to treatments currently in use can reduce the tumour considerably, defining anti-androgenic treatments as a novel effective therapeutic target. Citation Format: Sara Caceres, Angela Alonso Diez, Gema Silvan, Maria J. Illera, Juan C. Illera. Combination of conventional therapies and antiandrogenic treatments as a succesful tool for triple negative breast cancer (TNBC) treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4362.

Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer.

To evaluate the prognostic role of androgen receptor (AR) expression in patients with TNBC. The effect of the AR expression level in tumor tissue on overall survival depending on clinical, histological and immunohistochemical characteristics of the tumor was evaluated in 116patients with metastatic TNBC. The independent prognostic value of AR expression in patients with TNBC of different stages was shown. The median overall survival was higher in patients with AR-positive tumors compared with AR-negative tumors (57months vs 27months, p < 0.0001). Five-year survival since diagnosis in the group with AR-positive TNBC was 47.6 ± 8.3% vs 20.0 ± 5.3% in the group with AR-negative TNBC (p < 0.05). The results of our study indicate a favorable impact of AR expression on the overall survival of TNBC patients.

Using of Androgen Receptor Expression as a Novel Potential Biomarker in Predicting Survival of Women with Metastatic Triple Negative Breast Cancer

Background and objective: The androgen receptor (AR) is a member of the steroid receptor subfamily with well-known biological and therapeutic importance in prostate cancer. There is evidence that the androgen signalling pathway may play a critical role also in normal and malignant breast tissue. They are highly expressed in triple negative breast cancer (TNBC) but it is not clear if AR expression is correlated with survival in advanced TNBC. Therefore, in the present study we investigated the prognostic value of AR expression in metastatic TNBC. Patients and methods: Stage IV TNBC was included in the analysis. Patients with poor performance status (ECOG>2) were excluded. Tumors with >10% nuclear-stained cells were considered to be positive for AR. Univariate and multivariate analyses were performed. Results: From a database of 208 TNBC patients, 24 cases of advanced TNBC were identified; out of 24 patients, 33% were AR positive. The median age at diagnosis was 61 years (range 30-78 years). All patients included in the study received first-line chemotherapy for their disease. Median progression free-survival (mPFS) and overall survival (OS) were 3.5 months (range 0.3-27.3 months) and 25.9 months (range 2.52-122.2 months), respectively. Univariate analysis showed that AR negative advanced TNBC had a significantly worse PFS (3.2 vs 7.9 months; p=0.02; HR=2.57, 95% CI 1.15-10.53) and OS (20.5 vs 47.4 months; p=0.01; HR=2.88, 95% CI 1.32- 9.43). Multivariate analysis confirms that AR expression was an independent prognostic factor of PFS (p=0.04; HR=2.19, 95% CI 1.52-5.91), as well as for OS (p=0.05; HR=2.21, 95% CI 0.98-2.55). Conclusions: Our preliminary results suggested that the assessment of AR expression may be a useful tool to identify patients with a good or a poor prognosis. Furthermore, since that about one third of metastatic TNBC expressed ARs, they may represent a target for novel potential treatment options in advanced TNBC.