MpBCs are morphologically heterogeneous, frequently triple-negative and resistant to chemotherapy. To better understand why MpBCs are resistant to chemotherapy, we investigated associations between response to NAST and clinical, morphologic, as well as molecular characteristics in a cohort of MpBC patients (pts).
19 MpBC pts were identified from a prospective cohort of 242 triple-negative breast cancer (TNBC) pts treated with anthracycline-based NAST. Histologic subtype of MpBC was determined by light microscopy. TNBC subtypes were determined using the Vanderbilt gene expression signatures (GES). Residual cancer burden (RCB) was assessed after surgery.
Of the 19 MpBCs, 37% (7/19) were matrix producing and 63% (12/19) were not. Analysis of GES revealed the following subtype distributions: mesenchymal (M)=32% (6/19), mesenchymal stem-like (MSL)=11% (2/19), basal-like 2 (BL2)=32% (6/19), immunomodulatory (IM)=11% (2/19), unstable (UNS)=11% (2/19), basal-like 1 (BL1)=5% (1/19). Fifty-seven percent (4/7) and 33% (4/12) of the matrix producing and non-matrix producing MpBCs were of the M/MSL subtype, respectively. Twenty-one percent (4/19) of pts had a pathologic complete response (pCR)/minimal residual disease (RCB-I) following NAST. MpBCs that were matrix producing or of the M/MSL subtype were associated with worse response to NAST as none (0/11) of the pts with MpBC that was matrix producing and/or of the M/MSL subtype had a pCR/RCB-I, compared with 50% (4/8) of the remaining pts (p = 0.018).Table: 228P
Associations between response to NAST and clinical, morphological as well as molecular characteristics
|pCR/RCB-I (n = 4)||RCB-II/III (n = 15)|
|Median age (range)||57.3 (42.4-67.2)||57.8 (34.2-74.0)|
|Mean tumor size - cm (SD)||2.4 (1.2)||4.7 (3.8)|
|Clinical nodal status|
|Negative - n (%)||4 (25)||12 (75)|
|Positive - n (%)||0||3 (100)|
|I - n (%)||2 (40)||3 (60)|
|II - n (%)||2 (20)||8 (80)|
|III - n (%)||0||4 (100)|
|1 - n (%)||0||1 (100)|
|2 - n (%)||1 (25)||3 (75)|
|3 - n (%)||3 (21)||11 (79)|
|Matrix producing - n (%)||0||7 (100)|
|Non-matrix producing - n (%)||4 (33)||8 (67)|
|M/MSL - n (%)||0||8 (100)|
|BL1/2 - n (%)||3 (43)||4 (57)|
|Other - n (%)||1 (25)||3 (75)|
Analysis of GES suggest that MpBC is enriched for subtypes less likely to achieve pCR/RCB-I with NAST (BL2, M, MSL). Matrix-producing (light microscopy) and the M/MSL subtypes (GES) appear to be associated with resistance to anthracycline-based NAST in MpBC.
Clinical trial identification
Legal entity responsible for the study
The University of Texas MD Anderson Cancer Center.
National Comprehensive Cancer Network (NCCN) Oncology Research Program, The MD Anderson Cancer Center Moonshots Program, CPRIT Multi-Investigator Research Award (MIRA).
All authors have declared no conflicts of interest.