Abstract P3-05-04: Impact of androgen receptor expression in fluoxymesterone-treated, estrogen receptor–positive metastatic breast cancer exposed to contemporary hormonal therapy
Authors: Kono M , Fujii T , Lyons GR , Huo L , Bassett R , Gong Y , Karuturi MS , Tripathy D , Ueno NT 
Published: March 2017

Abstract
Background: The use of the nonselective androgen fluoxymesterone in patients with metastatic breast cancer (MBC) diminished after the 1960s because of its adverse events and a limited understanding of its biological effects. Although fluoxymesterone has had efficacy against tamoxifen-resistant disease in clinical studies, its role in the era of contemporary hormonal therapy is unclear. Recent studies have shown that the androgen–androgen receptor (AR) complex acts as a suppressor of estrogen receptor (ER)+ breast cancer. We hypothesized that fluoxymesterone is effective against MBC that progresses despite contemporary hormonal therapy and that the drug has more clinical benefit in patients with ER+AR+ disease than in patients with ER+AR- disease. We evaluated the survival outcomes of patients with MBC who received fluoxymesterone after contemporary hormonal therapy failed and evaluated the association between ER/AR status and survival outcomes in these patients.
Methods and Materials: We included 103 patients treated with fluoxymesterone who had already received at least one prior hormonal or cytotoxic treatment for MBC between January 1, 2000, and December 31, 2014, at a single institution. A pathologist reviewed these patients' tumors' ER and AR expression levels by immunohistochemical staining. Progression-free survival (PFS) was defined from the start of fluoxymesterone treatment to the date of disease progression or last follow-up. We used Cox regression analysis to examine univariate and multivariate correlates of PFS.
Results: Patients received a median of 3 (range: 0-10) prior hormonal therapies (aromatase inhibitors, tamoxifen, and/or fulvestrant) before fluoxymesterone. Of the 103 patients, 33 (32%) discontinued fluoxymesterone because of physician decision or adverse events, which included toxicity in 14 patients, and 70 (68%) were eligible for tumor response assessment by Response Evaluation Criteria in Solid Tumors. Of these 70 patients, 2 (3%) had a complete response, 7 (10%) had a partial response, and 21 (30%) had stable disease for at least 6 months, yielding a clinical benefit rate of 43%. The median PFS was 3.9 months (95% confidence interval: 3.2–5.3 months). The multivariate analysis revealed no significant association between PFS and the type or number of prior treatments. Thirty-nine patients (38%) had archived tumor slides available for AR staining. All 39 patients had ER+ disease; 5 had ≤1%, 5 had &gt;1% but &lt;10%, 18 had ≥10%, and 11 had no AR nuclear expression. AR positivity defined by the presence of any AR+ cells, ≥1% AR+ cells, or ≥10% AR+ cells was not significantly associated with survival outcome.
Conclusions: Fluoxymesterone showed objective tumor response and prolonged control of ER+ MBC refractory to contemporary endocrine therapy. The number and type of prior treatments did not impact the drug's clinical benefit, and AR+ status did not influence the clinical outcome. Fluoxymesterone should be considered for patients whose ER+ MBC progresses despite contemporary hormonal therapy, regardless of their AR status.
Citation Format: Kono M, Fujii T, Lyons GR, Huo L, Bassett R, Gong Y, Karuturi MS, Tripathy D, Ueno NT. Impact of androgen receptor expression in fluoxymesterone-treated, estrogen receptor–positive metastatic breast cancer exposed to contemporary hormonal therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-05-04.