Impact of androgen receptor expression in fluoxymesterone-treated estrogen receptor-positive metastatic breast cancer refractory to contemporary hormonal therapy.
The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients.



We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting.



A median of 3 (range 1-10) hormonal therapies (aromatase inhibitors, tamoxifen, and/or fulvestrant) were received before fluoxymesterone; 33 patients discontinued fluoxymesterone before progression because of physician decision or adverse events including toxicity in 14 patients. Of the remaining 70 patients, 2 (3 %) had complete response, 7 (10 %) partial response, and 21 (30 %) stable disease for at least 6 months, yielding a clinical benefit rate of 43 %. The median PFS was 3.9 months (95 % CI 3.2-5.3 months). Multivariate analysis revealed no significant association between PFS and the type or number of prior systemic treatments. All 39 patients who had archived tumor slides available for AR staining had ER + carcinoma; 10 had ≥1 % but <10 %, 18 had ≥10 %, and 11 had no AR nuclear expression. AR positivity with various cutoffs (i.e. any AR + cells, ≥1 % AR + cells, or ≥10 % AR + cells) was not significantly associated with survival outcome.



Fluoxymesterone can be considered for patients whose ER + MBC progresses on contemporary hormonal therapy, regardless of the level of AR expression.
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA.|Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.|Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi Minamiku, Hiroshima, 7348553, Japan.
Miho
M
Kono
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA.|Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Takeo
T
Fujii
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Genevieve Ray
GR
Lyons
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Lei
L
Huo
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Roland
R
Bassett
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yun
Y
Gong
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA.
Meghan Sri
MS
Karuturi
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA.|Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Debu
D
Tripathy
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA. nueno@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. nueno@mdanderson.org.
Naoto T
NT
Ueno
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D005260:Female; D005474:Fluoxymesterone / Q000627:therapeutic use*; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D005474:Fluoxymesterone
Androgen receptor; Estrogen receptor; Fluoxymesterone; Hormonal therapy; Metastatic breast cancer