Purpose: to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of PTEN are associated with response to anti-Her2 treatment in breast cancer (BC). Experimental Design: we analyzed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive IBC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic IBC (MBC) and 55 early stage IBC, with complete clinical information (mean follow-up 37, 66 and 32 months, respectively). Results: PI3KCA hot-spot mutations were observed in 25 cases (19.4%): 12 (9.3%) in exon 9 and 13 (10.1 %) in exon 20. No relationships were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC we could not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28%), 3 (12.5%) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. Conclusion: PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy.
PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy.
Eccher, Claudio;
2012-01-01
Abstract
Purpose: to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of PTEN are associated with response to anti-Her2 treatment in breast cancer (BC). Experimental Design: we analyzed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive IBC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic IBC (MBC) and 55 early stage IBC, with complete clinical information (mean follow-up 37, 66 and 32 months, respectively). Results: PI3KCA hot-spot mutations were observed in 25 cases (19.4%): 12 (9.3%) in exon 9 and 13 (10.1 %) in exon 20. No relationships were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC we could not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28%), 3 (12.5%) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. Conclusion: PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
