Functional Subtyping with BluePrint 80-gene profile identifies distinct triple positive subtypes with and without trastuzumab/pertuzumab/chemo-sensitivity

Author(s): Pat Whitworth, Peter Beitsch, Paul Baron, Michael C Rotkis, James V Pellicane, Mary Murray, Carrie L Dul, Angela M Mislowsky, Charles H Nash, Paul D Richards, Laura A Lee, Lisette Stork-Sloots, Femke de Snoo, Sarah Untch, Mark Gittleman, Stephanie Akbari, Jennifer Beatty

Background and Aim

Classification into molecular subtypes is important for the selection of therapy for patients with breast cancer. Previous analyses demonstrated that breast cancer subtypes have distinct clinical outcome (Glück, BCRT 2013). The aim of the prospective NBRST study is to compare a multi-gene classifier to conventional local IHC/FISH subtyping to predict chemosensitivity as defined by pathological Complete Response (pCR).  pCR: ypT0/isN0

Conclusions:

  • Compared to conventional IHC/FISH, BluePrint functional subtyping reclassifies about 1 in 5 tumors, yielding significantly better correlation with NCT responsiveness (BP HER2 and Basal) and resistance (BP Luminal).
  • BluePrint identifies two distinct subgroups within the conventional HER2+/ER+ group; ~50% of these tumors are BP Luminal and relatively resistant to NCT/trastuzumab.
  • Pertuzumab overcame resistance to NCT/trastuzumab in a substantial proportion of the IHC/FISH HER2+/BP Luminal subgroup; indicated by a significantly increased pCR rate.

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ASCO 2015 Abstract #596