Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer

Lyalkin, S.; Verevkina, N.O.; Alekseyenko, O O; Syvak, L.А.

doi:10.32471/exp-oncology.2312-8852.vol-42-no-2.14579

Cited by 8 publications

(12 citation statements)

References 13 publications

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“…It has been observed that AR negative TNBCs are more likely to have lymph node metastases than AR positive tumors. 33 , 38 , 39 In addition, multiple studies find that AR negative tumors are more likely to present at a higher grade and stage than AR positive tumors. 29 , 30 , 34 , 35 , 37 From the limited research on TNBC histological subtypes, IDC is the most common, with one paper presenting that AR negative tumors are more likely to be ductal than AR positive tumors.…”

Section: Discussionmentioning

confidence: 99%

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Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Dubrava,

Kyaw,

Newman

et al. 2023

BCTT

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Purpose Triple negative breast cancer (TNBC) is a breast carcinoma subtype that neither expresses estrogen (ER) and progesterone receptors (PR) nor the human epidermal growth factor receptor 2 (HER2). Patients with TNBC have been shown to have poorer outcomes mainly owing to the limited treatment options available. However, some studies have shown TNBC tumors expressing androgen receptors (AR), raising hopes of its prognostic role. Patients and Methods This retrospective study investigated the expression of AR in TNBC and its relationship with known patient demographics, tumor and survival characteristics. From the records of 205 TNBC patients, 36 had available archived tissue samples eligible for AR staining. For statistical purposes, tumors were classified as either “positive” or “negative” for AR expression. The nuclear expression of AR was scored by measuring the percentage of stained tumor cells and its staining intensity. Results AR was expressed by 50% of the tissue samples in our TNBC cohort. The relationship between AR status with age at the time of TNBC diagnosis was statistically significant, with all AR positive TNBC patients being greater than 50 years old (vs 72.2% in AR negative TNBC). Also, the relationship between AR status and type of surgery received was statistically significant. There were no statistically significant associations between AR status with other tumor characteristics including “TNM status”, tumor grade or treatments received. There was no statistically significant difference in median survival between AR negative and AR positive TNBC patients (3.5 vs 3.1 years; p = 0.581). The relationship between OS time and AR status (p = 0.581), type of surgery (p = 0.061) and treatments (p = 0.917) were not statistically significant. Conclusion The androgen receptor may be an important prognostic marker in TNBC, with further research warranted. This research may benefit future studies investigating receptor-targeted therapies in TNBC.

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Section: Discussionmentioning

confidence: 99%

“… 8 , 34 , 36 , 41 This includes a better OS time after three and five years for patients with AR+ tumors than AR- tumors. 37 , 38 , 41 Appendix C compares the OS times of TNBC patients from different studies. However, these studies do not examine whether patient treatment choices affected their respective survival times.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Dubrava,

Kyaw,

Newman

et al. 2023

BCTT

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“…In a meta-analysis, AR expression in TNBC was associated with longer DFS and OS [ 35 ]. In a study based on 116 metastatic TNBC cases, AR positive expression was found to be an independent prognostic protective factor, as AR positivity (AR > 10%) was associated with higher 5-year survival [ 14 ]. However, in a study of 263 patients with primary early TNBC, AR expression and its correlation with prognosis was evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…However, the studies reporting prognostic implications of AR expression in TNBC and HER2 positive subtypes had paradoxical results. Some studies indicated AR positivity was associated with a better outcome [ 14 – 16 ], others reported a worse prognosis [ 17 – 19 ]. Moreover, it also has been reported that there was no correlation between AR status and outcome in TNBC [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

et al. 2023

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Background Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. Methods We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. Results The positive rates of AR expression in HR + /HER2-, HR + /HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR + /HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR + /HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. Conclusions AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR + /HER2- subtype and in HR + /HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P = 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR + /HER2- and HR + /HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis.

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“…Las líneas celulares de CMTN positivos al AR a menudo expresan mutaciones de PI3KCA, volviéndolos más sensibles a los inhibidores de PI3K/mTOR. Es importante destacar que los AR en el CMTN interactúan con la poli(ADPribosa) polimerasa 1 (PARP1) y BRCA1, reguladores del ciclo celular BRCA1 y PARP1 activan la transcripción de genes AR estimulando el crecimiento tumoral (Leung y Sadar, 2017;Lyalkin et al, 2020).…”

Section: Andrógenos Estructura Y Función De Los Andrógenosunclassified

Efecto de los andrógenos sobre la rugosidad, a nivel nanométrico, de la membrana plasmática de células de cáncer de mama triple-negativas

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Microscopía de fuerza atómica AKT: Proteína cinasa en serina/treonina AR: Receptor de andrógenos (por sus siglas en idioma inglés) ARE: Elementos de respuesta de andrógenos (por sus siglas en idioma inglés) ARN pol II: ARN polimerasa II AuNP: Nanopartículas de oro (por sus siglas en idioma inglés) B-RAF: Protooncogén de cinasas serina/treonina BRCA1: Cáncer de mama de inicio temprano 1 (por sus siglas en idioma inglés) Cai 2+ : Calcio intracelular CaM: Cáncer de mama CaP: Cáncer de próstata Cav-1: Caveolina-1 CCD: Dispositivo de carga acoplada (por sus siglas en idioma inglés) CD24: Antígeno codificado por el gen CD24 CD44: Antígeno codificado por el gen CD44 en el cromosoma 11 Chol: Colesterol Cl -: Ion cloro CMTN: Cáncer de mama triple negativo, por sus siglas en idioma inglés de Triple Negative Brest Cancer CoA: Coactivadores C-RAF: Protooncogén de cinasas serina/treonina CRPCa: Tumor resistente a la castración (por sus siglas en idioma inglés) DBD: Dominio de unión al ADN (por sus siglas en idioma inglés

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Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer

Cited by 8 publications

References 13 publications

Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

Efecto de los andrógenos sobre la rugosidad, a nivel nanométrico, de la membrana plasmática de células de cáncer de mama triple-negativas

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