Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy

Locati, Laura D.; Perrone, Francesco; Cortelazzi, Barbara; Imbimbo, Martina; Bossi, Paolo; Potepan, Paolo; Civelli, Enrico; Rinaldi, Gaetana; Quattrone, Pasquale; Licitra, Lisa; Pilotti, Silvana

doi:10.4161/cbt.28410

Cited by 24 publications

(14 citation statements)

References 18 publications

(18 reference statements)

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“…Using a cutoff value of 20% nuclear staining of tumor cells, we found that AR-negative patients had a significantly worse prognosis than AR-positive patients, although the ERβ expression did not influence the survival. The role of AR in the generation or progression of SDC has been under investigated [ 29 ]; however, AR has recently become a key target of androgen deprivation treatment for this tumor [ 2 , 11 , 21 , 24 , 33 , 34 ], as with prostate cancer. Further studies will be required to verify the effect and potential resistance mechanisms for this therapy.…”

Section: Discussionmentioning

confidence: 99%

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

et al. 2017

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Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR− and CK5/6+ were associated with shorter progression-free survival (P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival (P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: ‘apocrine A’ (AR+/HER2−/Ki-67-low) (24%), ‘apocrine B’ (AR+/HER2−/Ki-67-high) (18%), ‘apocrine HER2’ (AR+/HER2+) (35%), ‘HER2-enriched’ (AR−/HER2+) (12%), and ‘double negative’ (AR−/HER2−) (11%). ‘Double negative’ was further subclassified into ‘basal-like’ (EGFR and/or CK5/6+) (7%) and ‘unclassified’ (3%). Consequently, patients with ‘apocrine A’ showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.

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Section: Discussionmentioning

confidence: 99%

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

et al. 2017

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“…Several case reports have shown a good effect of ADT alone in patients with AR-positive SDC or AC NOS, including stable disease for several months as well as cases of complete remission [ 43 , 60 , 61 ]. A few patients with SDC or AC NOS, who initially responded to a combination of bicalutamide and triptorelin but had a relapse, then showed a response to subsequent abiraterone, suggesting resistance mediated by the reactivation of AR signaling during ADT treatment [ 62 , 63 ]. ADT has also been combined with either definitive RT or palliative chemotherapy with robust responses in several single case reports of SGC [ 64 , 65 ].…”

Section: Anti-androgen Therapy In Patients With Sgcmentioning

confidence: 99%

Androgen Receptor Signaling in Salivary Gland Cancer

Dalin

Watson

et al. 2017

Cancers

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Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma. Successful treatment with anti-androgen therapy in other androgen receptor-positive malignancies such as prostate and breast cancer has inspired researchers to investigate this treatment in salivary gland cancer as well. In this review, we describe the prevalence, biology, and therapeutic implications of androgen receptor signaling in salivary gland cancer.

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“…However, the experience with abiraterone is limited in this setting. In a recent report by Locati et al, abiraterone showed remarkable activity in two patients with AR expressing recurrent and metastatic salivary gland carcinoma ( 14 ). In our case, complete anti-androgen blockade with bicalutamide plus LHRH was chosen as the optimal therapy at the time, based on AR expression of the tumor and reported literature on salivary gland carcinomas.…”

Section: Discussionmentioning

confidence: 97%

Androgen-Receptor Positive Lacrimal Sac Adenocarcinoma Demonstrating Long-Lasting Response to LHRH Analog Plus Abiraterone Treatment

et al. 2015

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Tumors arising at the lacrimal sac are extremely rare, as a limited number of cases have been reported worldwide. They are commonly primary and the majority of them are malignant and epithelial in origin. Adenocarcinomas account for a small percentage of these tumors. Treatment of local disease mainly includes complete surgical resection. However, metastatic disease has a poor prognosis and the development of new treatment strategies is highly important. Research efforts mainly focus on the identification of molecular targets for therapy. Herein, we describe for the first time a case of a patient with an androgen receptor expressing adenocarcinoma of the lacrimal sac that had an impressive response to abiraterone.

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Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy

Cited by 24 publications

References 18 publications

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

Androgen Receptor Signaling in Salivary Gland Cancer

Androgen-Receptor Positive Lacrimal Sac Adenocarcinoma Demonstrating Long-Lasting Response to LHRH Analog Plus Abiraterone Treatment

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