Phase II Trial of Bicalutamide in Patients with Androgen Receptor–Positive, Estrogen Receptor–Negative Metastatic Breast Cancer

Gucalp, Ayca; Tolaney, Sara M.; Isakoff, Steven J.; Ingle, James N.; Liu, Minetta C.; Carey, Lisa A.; Blackwell, Kimberly; Rugo, Hope S.; Nabell, L.; Forero, Andres; Stearns, Vered; Doane, Ashley S.; Danso, Michael A.; Moynahan, Mary Ellen; Momen, Lamia F.; Gonzalez, Joseph; Akhtar, Arooj; Giri, Dilip; Patil, Sujata; Feigin, Kimberly N.; Hudis, Clifford A.; Traina, Tiffany A.

doi:10.1158/1078-0432.ccr-12-3327

Cited by 614 publications

(539 citation statements)

References 36 publications

(36 reference statements)

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“…Bicalutamide, an oral non-steroidal antiandrogen that competitively inhibits the binding of androgens with AR, has shown a proof-of-principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive BC (Gucalp et al 2013). One case of complete response to bicalutamide was recently reported in a patient with metastatic triple-negative, AR-positive BC (Arce-Salinas et al 2016).…”

Section: Ar-targeting Therapy In Triple-negative/lar Bcmentioning

confidence: 99%

Androgen receptor signaling pathways as a target for breast cancer treatment

Pietri¹,

Conteduca²,

Andreis³

et al. 2016

Endocrine-Related Cancer

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The androgen receptor (AR) is a ligand-dependent transcription factor, and its effects on breast range from physiological pubertal development and age-related modifications to cancer onset and proliferation. The prevalence of AR in early breast cancer is around 60%, and AR is more frequently expressed in ER-positive than in ER-negative tumors. We offer an overview of AR signaling pathways in different breast cancer subtypes, providing evidence that its oncogenic role is likely to be different in distinct biological and clinical scenarios. In particular, in ER-positive breast cancer, AR signaling often antagonizes the growth stimulatory effect of ER signaling; in triple-negative breast cancer (TNBC), AR seems to drive tumor progression (at least in luminal AR subtype of TNBC with a gene expression profile mimicking luminal subtypes despite being negative to ER and enriched in AR expression); in HER2-positive breast cancer, in the absence of ER expression, AR signaling has a proliferative role. These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/ AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors. Only the ongoing and future prospective clinical trials will allow us to establish which agents are the best option in every specific condition, keeping in mind that there is evidence of opposite androgens and AR agonist/antagonist drug effects on cell proliferation particularly in AR-positive/ER-positive tumors.

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Section: Ar-targeting Therapy In Triple-negative/lar Bcmentioning

confidence: 99%

Androgen receptor signaling pathways as a target for breast cancer treatment

Pietri¹,

Conteduca²,

Andreis³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

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“…44 In addition, multiple clinical trials currently underway for patients with TNBC have shown promising preliminary results with AR-targeted therapies against TNBCs with a higher percentage of AR þ cells. 45 We, therefore, propose testing for AR expression in all metastatic/recurrent TNBCs and primary TNBCs that do not completely respond to chemotherapy to help guide management decisions. …”

Section: Prognostic and Predictive Values Of Androgen Receptor In Tnbcsmentioning

confidence: 99%

Update on Immunohistochemical Analysis in Breast Lesions

Peng¹,

Butt²,

Chen³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The utility of immunohistochemistry (IHC) in breast lesions needs to be updated with exceptions among these lesions. Biomarker studies with IHC in triple-negative breast carcinoma may help develop targeted therapies for this aggressive breast cancer. The distinction of metastatic lung adenocarcinoma to the breast and invasive breast carcinoma has significant prognostic and therapeutic implications. The determination can be challenging because both primary tumors can express estrogen receptor and/or HER2 by IHC, creating a diagnostic dilemma.Objectives.-To provide a practical update on the use of IHC markers in differential diagnoses in breast lesions, including benign, atypical, precancerous, and malignant tumors; to highlight recently published research findings on novel IHC markers in triple-negative breast carcinoma cases; and to reinforce the importance of IHC use as an ancillary tool in distinguishing metastatic lung adenocarcinoma to the breast from primary breast carcinoma using real case examples.Data Sources.-PubMed (US National Library of Medicine, Bethesda, Maryland) literature review and authors' research data and personal experiences were used in this review.Conclusions.-Immunohistochemistry has an important role in making differential diagnoses in breast lesions in morphologically equivocal settings; recognizing IHC expression status in the exceptions among these lesions will aid in the correct diagnosis of challenging breast cases. Studies suggest that androgen receptor, p16, p53, GATA3, and PELP1 may have potential diagnostic, prognostic, and predictive value in triple-negative breast carcinoma cases; these findings may provide insight and a greater understanding of the tumor biology in triple-negative breast carcinomas. In distinguishing metastatic estrogen receptor-positive or HER2 þ lung adenocarcinoma to the breast from primary breast carcinoma, napsin A, TTF-1, and GATA3 comprise a useful IHC panel.

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“…Some studies show no prognostic value of AR in ER -and/or TNBC, whereas others report either improved or worsened outcomes for breast cancer patients with AR positive (AR + ) in ERand/or TNBC as reviewed by McNamara et al (16). However, a clinical phase II trial recently showed promising results for the anti-androgen bicalutamide in AR + /ER -/PR -metastatic 4 breast cancer, high-lighting AR as a promising predictive marker in breast cancer treatment (17). Another anti-androgen, enzalutamide, is currently being tested in an ongoing clinical trial (ClinicalTrials.gov identifier: NCT01597193).…”

Section: Introductionmentioning

confidence: 99%

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

Elebro

Butt

Dorkhan

et al. 2014

Cancer Causes Control

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Link to publication Citation for published version (APA): Elebro, K., Butt, S., Dorkhan, M., Jernström, H., & Borgquist, S. (2014). Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort. Cancer Causes and Control, 25(8), 945-957. DOI: 10.1007/s10552-014-0394-2 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal

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Phase II Trial of Bicalutamide in Patients with Androgen Receptor–Positive, Estrogen Receptor–Negative Metastatic Breast Cancer

Cited by 614 publications

References 36 publications

Androgen receptor signaling pathways as a target for breast cancer treatment

Androgen receptor signaling pathways as a target for breast cancer treatment

Update on Immunohistochemical Analysis in Breast Lesions

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

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