Abstract P3-06-14: Serum activin A and response to the aromatase inhibibitor (AI) letrozole versus tamoxifen in metastatic breast cancer
Authors: Jensen Meghan , Kang Ashley , Ali Suhail M , Leitzel Kim , Garg Ashwani , Rogerio Jaqueline , Chen David , Hall Raymond , Hofsess Scott , Chaudri-Ross Hilary A , Bade Nicholas , Carney Walter P , Lipton Allan 
Published: May 2015

Abstract
Introduction: The prognostic and predictive utility of pretreatment serum activin A (TGF-B superfamily ligand) was correlated with the response of first-line metastatic breast cancer patients (MBC) in the phase 3 randomized trial of letrozole vs. tamoxifen.
Methods: 555 ER+ first-line MBC patients had pretreatment serum available for activin A ELISA (R&D Systems). Clinical outcomes were analyzed using Cox proportional hazards modeling. Actin A levels were analyzed using continuous and categorical (median cutpoint) pretreatment serum activin A levels. A pretreatment serum activin A analysis was performed within the normal (not elevated, &lt;15 ng/ml) pretreatment serum HER2 patient subgroup since tumor HER2 status was not available in this older clinical trial.
Results: Serum activin A had a median of 971 pg/ml and an interquartile range of 623 and 1751 pg/ml. In the total population with available serum (n=555), patients with higher serum activin A (&gt; median) had significantly reduced objective response rate (ORR)(17.33% vs 34.6%, Odds Ratio (OR)=0.4; p&lt;0.0001) and reduced clinical benefit rate (CBR)(33% vs 53%, OR= 0.45; p&lt;0.0001), as well as significantly shorter time to progression (TTP) [median 5.88 vs 10.98 mo, HR=1.69; p&lt;0.0001], and reduced overall survival (OS) (median 22.78 vs 48.59 mo, HR=2.43; p&lt;0.0001) compared to those with lower serum activin A (&lt;median) (table). The results were similar in subgroup analyses within treatment arms (letrozole or tamoxifen), as well as within the subgroup of patients with normal (not elevated, &lt;15 ng/ml) pretreatment serum HER2 levels (table).
In the total population with available serum (n=555), multivariate analysis for TTP revealed that high serum activin A was a significant adverse prognostic factor (HR=1.46, p&lt;0.001). Multivariate analysis for OS also revealed that high serum activin A was an independent adverse prognostic factor (HR 1.78, p&lt;0.0001).
Outcome (Serum activin A by median cutpoint, high vs. low)TTPOSCohortPatientsHRpHRpTotal Population5551.69&lt;0.00012.43&lt;0.0001Letrozole Arm2741.580.0012.24&lt;0.0001Tamoxifen Arm2611.92&lt;0.00012.6&lt;0.0001Serum HER2 (not elevated)3951.55&lt;0.00012.45&lt;0.0001
Conclusions: Patients with high pretreatment serum activin A levels had a significantly reduced ORR, CBR, TTP and OS compared to patients with low serum activin A. The results were similar within the letrozole or tamoxifen treatment arms, and within the serum HER2 not-elevated subgroups. High pretreatment serum activin A level is associated with relative resistance to hormone therapy in first-line metastatic breast cancer.
Citation Format: Meghan Jensen, Ashley Kang, Suhail M Ali, Kim Leitzel, Ashwani Garg, Jaqueline Rogerio, David Chen, Raymond Hall, Scott Hofsess, Hilary A Chaudri-Ross, Nicholas Bade, Walter P Carney, Allan Lipton. Serum activin A and response to the aromatase inhibibitor (AI) letrozole versus tamoxifen in metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-14.