Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. Besides emerging preclinical evidence suggested that TNBC cells seem particularly sensitive to mTOR inhibitors, especially the androgen receptor-positive (AR+) TNBC cell lines. In the present study, we explored the correlation of AR and p-mTOR (the activate form of mTOR) expressions with clinical, pathological and molecular features and their impact on prognosis in early TNBC. Patients and Methods: Between January 2009 and December 2015, all consecutive patients who were diagnosed and completed the treatment of invasive early TNBC at our institution were eligible for this analysis. Results: 180 TNBC patients were included in the analysis. 24.4% of them were AR+. Expression of AR+ was significantly associated with lympho-vascular invasion (p=0.04) and metastases of axillary nodes (p=0.05). Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p=0.30) or overall survival (p=0.26). Of 98 patients, 32.6% of cases were p-mTOR positive. Univariate survival analysis revealed that p-mTOR positivity was not associated with DFS (p=0.74) and OS (p=0.95). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). Conclusions: The expression of AR is associated with some biological features of TNBC, such as lympho-vascular invasion and metastasis of axillary nodes; nevertheless the prognostic significance of AR was not documented in our analysis. Of interest, our preliminary results showed the strong correlation between p-mTOR immunostaining and AR positivity, suggesting that may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumour progression.
Background: I carcinomi mammari triplo negativi (TNBC) presentano un comportamento clinico aggressivo dovuto anche alla mancanza di terapie target. La recente identificazione di un sottotipo molecolare correlato con l’attivazione del recettore degli androgeni (AR), ha suscitato interesse nel mondo scientifico per il possibile impiego di terapie anti-androgeniche in questo sottogruppo di neoplasie mammarie. Evidenze pre-cliniche evidenziano inoltre un’iperattivazione della via di segnale mediata da mTOR nei TNBC AR+. Il nostro studio ha voluto valutare l’incidenza di positività di AR e della forma attiva di mTOR (p-mTOR) su 180 TNBC, valutandone la correlazione con le caratteristiche cliniche, patologiche e molecolari, nonché il loro significato prognostico. Pazienti e metodi: La nostra analisi è stata condotta su 180 pazienti con diagnosi di TNBC stadio I-III afferite c/o la Clinica di Oncologia degli Ospedali Riuniti di Ancona tra gennaio 2009 e dicembre 2015. Risultati: AR è risultato espresso nel 24,4% dei casi e non ha mostrato una correlazione prognostica con la sopravvivenza globale (p=0.26) e libera da malattia (p=0.30). L’espressione di AR è risultata più frequentemente associata alla presenza di metastasi ai linfonodi ascellari (p=0.05) e di invasione vascolare (p=0.04). Analogamente i dati preliminari su 98 pazienti non hanno evidenziato un ruolo prognostico di p-mTOR, che è tuttavia risultato significativamente più espresso nei TNBC di piccole dimensioni (p=0.03) con AR-positivi (p=0.04). Conclusioni: AR non sembra avere un significato prognostico nei TNBC. I risultati preliminari su p-mTOR non mostrano un’associazione con la prognosi delle pazienti; tuttavia la presenza di una correlazione significativa tra l’attivazione di mTOR e AR potrebbe rappresentare il presupposto terapeutico per l’utilizzo di farmaci che inducono una doppia inibizione sia su AR che su mTOR con un sinergico effetto anti-proliferativo sulle cellule tumorali.
Espressione di p-mTOR e del recettore degli androgeni nei tumori mammari triplo negativi: significato clinico e potenziali prospettive terapeutiche / Pistelli, Mirco. - (2016 Feb 25).
Espressione di p-mTOR e del recettore degli androgeni nei tumori mammari triplo negativi: significato clinico e potenziali prospettive terapeutiche
Pistelli, Mirco
2016-02-25
Abstract
Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. Besides emerging preclinical evidence suggested that TNBC cells seem particularly sensitive to mTOR inhibitors, especially the androgen receptor-positive (AR+) TNBC cell lines. In the present study, we explored the correlation of AR and p-mTOR (the activate form of mTOR) expressions with clinical, pathological and molecular features and their impact on prognosis in early TNBC. Patients and Methods: Between January 2009 and December 2015, all consecutive patients who were diagnosed and completed the treatment of invasive early TNBC at our institution were eligible for this analysis. Results: 180 TNBC patients were included in the analysis. 24.4% of them were AR+. Expression of AR+ was significantly associated with lympho-vascular invasion (p=0.04) and metastases of axillary nodes (p=0.05). Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p=0.30) or overall survival (p=0.26). Of 98 patients, 32.6% of cases were p-mTOR positive. Univariate survival analysis revealed that p-mTOR positivity was not associated with DFS (p=0.74) and OS (p=0.95). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). Conclusions: The expression of AR is associated with some biological features of TNBC, such as lympho-vascular invasion and metastasis of axillary nodes; nevertheless the prognostic significance of AR was not documented in our analysis. Of interest, our preliminary results showed the strong correlation between p-mTOR immunostaining and AR positivity, suggesting that may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumour progression.File | Dimensione | Formato | |
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