scholarly journals Is Androgen Receptor a predicitive biomarker of response to antiestrogen therapy in advanced breast cancer?

2017 ◽  
Vol 28 ◽  
pp. vii22
Author(s):  
S. Ravaioli ◽  
A. Rocca ◽  
G. Bronte ◽  
M. Puccetti ◽  
M.M. Tumedei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Advanced Breast Cancer ◽  
Advanced Breast ◽  
Antiestrogen Therapy

Is androgen receptor useful to predict the efficacy of anti-estrogen therapy in advanced breast cancer?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1042-1042 ◽  
Author(s):  
Andrea Rocca ◽  
Giuseppe Bronte ◽  
Sara Ravaioli ◽  
Maurizio Puccetti ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Advanced Breast Cancer ◽  
Cox Regression ◽  
Estrogen Therapy ◽  
Advanced Breast ◽  
Categorical Variables ◽  
First Line ◽  
Primary Tumors ◽  
Best Response

1042 Background: The androgen receptor (AR) is widely expressed in breast cancers but its role in estrogen receptor (ER)-positive tumors is still controversial. However, the AR/ER ratio may impact prognosis and the response to antiestrogen endocrine therapy (ET). Methods: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced breast cancer (ABC). We evaluated patients treated with first-line ET (2002–2011), excluding those receiving concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy. ER, progesterone receptor (PgR), Her2, Ki67 and AR expression was determined by immunohistochemistry. A cut-off of < 1% immunostained cells was used to categorize AR expression. AR expression was analyzed in relation to the other conventional biomarkers (ER, PgR, Her2 and Ki67), best response (CR, PR, SD, PD), and time to progression (TTP) (months). TTP was estimated using the Kaplan-Meier method and compared with the log-rank test. Hazard ratios and their 95% confidence intervals (95% CI) were estimated using the Cox regression model. The Chi-square test was used to evaluate correlations between categorical variables and best response. p values < 0.05 were considered statistically significant. Results: Of the 102 evaluable patients (93% were treated with an aromatase inhibitor), biomarkers were assessed in primary tumors in 70 cases, in metastases in 49 and in 17 in both). Median TTP was 17 months (95% CI 14-21.5, median follow-up 75 months). The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR expression. Differences in TTP according to AR status were not statistically significant. AR/PgR ≥ 0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.030). AR status in primary tumors or metastases was not associated with PD as best response. In contrast, Ki67 > 20% and PgR < 10% showed a significant association with PD as best response. Using a cut off of ≤10% for AR expression, results did not change. Conclusions: AR expression does not appear to be useful to predict the efficacy of ET in ABC. Ki67 and PgR exert a greater impact on the efficacy of hormone therapy than AR.

scholarly journals Androgen receptor in advanced breast cancer: is it useful to predict the efficacy of anti-estrogen therapy?

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Giuseppe Bronte ◽  
Andrea Rocca ◽  
Sara Ravaioli ◽  
Maurizio Puccetti ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Advanced Breast Cancer ◽  
Estrogen Therapy ◽  
Advanced Breast

Superior Efficacy of Letrozole Versus Tamoxifen as First-Line Therapy for Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Study of the International Letrozole Breast Cancer Group

2001 ◽  
Vol 19 (10) ◽  
pp. 2596-2606 ◽  
Author(s):  
Henning Mouridsen ◽  
Mikhail Gershanovich ◽  
Yan Sun ◽  
Ramón Pérez-Carrión ◽  
Corrado Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Clinical Benefit ◽  
Advanced Breast ◽  
First Line ◽  
Once Daily ◽  
First Line Therapy ◽  
Line Therapy ◽  
Antiestrogen Therapy

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor– and/or progesterone receptor–positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P = .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P = .0006), as was the rate of clinical benefit (49% v 38%; P = .001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Efficacy and Safety of Targeting Androgen Receptor in Advanced Breast Cancer: A Systematic Review

2019 ◽  
Vol 15 (3) ◽  
pp. 197-206
Author(s):  
Loay Kassem ◽  
Kyrillus S. Shohdy ◽  
Nafie F. Makady ◽  
Dalal S. Salem ◽  
Nadia Ebrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Androgen Receptor ◽  
Advanced Breast Cancer ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Receptor Modulator ◽  
Complex Signaling ◽  
Elevated Transaminases

Background::Androgen receptor (AR) upstreams complex signaling pathways that regulate cell proliferation and contribute to breast tumorignensis. Several clinical trials were initiated to investigate the clinical relevance of targeting AR especially in hormone-receptor-negative breast cancer.Methods::The search was performed in PubMed and the meeting libraries of ASCO, ESMO, SABCS, ImpakT congresses from January 2005 to July 2017. The following key words were used: Breast cancer, Androgen receptor, androgen agonist/antagonist, Flutamide, Abiraterone, Bicalutamide, Enzalutamide, Enobosarm, selective androgen receptor modulator.Results::Screening of title/abstracts yielded a total of 20 relevant results. Of those, twelve studies were found eligible: eleven clinical trials along with one case report. Response rates ranged from 0 to 12% while clinical benefit rates reached up to 35% in 2 studies (with enzalutamide and enobosarm). Progression-free survival ranged from 2.8 to 4.5 months. The most widely used cutoff for AR expression was 10%. High expression of AR was associated with more clinical benefit. Regarding safety, anti-androgens were generally well tolerated with hot flushes, elevated transaminases and fatigue being the most commonly reported across all agents.Conclusion::Androgen receptor pathway targeting in advanced breast cancer remains a valid option with reasonable clinical benefit in non-selected patients. Future studies are needed to define an AR addicted cohort with better responses and outcome.

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