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Mesenchymal/metaplastic breast cancers (MpBCs) are often triple-negative (TNBC), and chemo-refractory, and can harbor phosphoinositide 3-kinase (PI3kinase) alterations; thus therapy with mTor inhibitors may demonstrate activity.

Patients with mesenchymal/MpBC treated with temsirolimus-based regimens were evaluated. Mutational analyses (polymerase chain reaction (PCR)-based DNA sequencing method, mass spectrometric detection (Sequenom MassARRAY), or next generation sequencing) as well as loss of phosphatase and tensin homolog (PTEN) (immunohistochemistry), were performed (archived tissue when available).

Twenty-three patients (one of whom was on two separate trials) were treated using temsirolimus-containing regimens: temsirolimus alone (n=1 patient) or combined with the following: liposomal doxorubicin and bevacizumab (DAT, n=18); liposomal doxorubicin (DT, n=1); paclitaxel and bevacizumab (TAT, n=2); paclitaxel (TT, n=1); carboplatin and bevacizumab (CAT, n=1). Response rate (CR+PR) was 25% across all regimens; 32% in the anthracycline-based regimens (DAT and DT (CR=2, PR=4; N=19). An additional two patients achieved stable disease (SD) >6 months [total SD>6 months/CR/PR=8 (33%)]. Molecular aberrations in the PI3K pathway were common: PIK3CA mutation=6/15 (40%), PTEN mutation=3/11 (27%), and PTEN loss=2/11 (18%). A point mutation in the NF2 gene (K159fs*16; NF2 alterations can activate mTor) was found in one patient who attained CR (3+ years). Of the eight patients who achieved SD>6 months/CR/PR, all 4 patients with available tissue had a molecular aberration that activate the PIK3CA/Akt/mTOR axis: PIK3CA mutation=2; PTEN loss=1; NF2 aberration=1;.

DAT has activity in MpBCs including complete CRs. Molecular aberrations that can activate the PI3K/Akt/mTOR axis are common in MpBC.

© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PMID:25878190