Abstract 98O
Background
In TNBC, the IM signature is highly enriched in immune cell markers and signaling which likely represents gene expression from both the tumor cells and infiltrating lymphocytes. High sTIL is independently associated with improved pCR rates in TNBC. The association between the IM subtype and sTIL in predicting pCR is not known.
Methods
Pretreatment core biopsies from 181 patients with early-stage TNBC enrolled on the ARTEMIS trial (NCT02276443) were evaluated for sTIL by H&E and Vanderbilt subtype using Affymetrix arrays and TNBCtype. sTIL was graded as low (<10%), moderate (10-30%) and high (>30%) using cut-points previously established to correlate with pCR. We calculated a point estimate and 95% confidence interval for the probability that a subject with given IM and TIL status will achieve pCR.
Results
The IM subtype was identified in fewer TNBCs with low or moderate sTIL (4 and 27%, respectively) than in those with high sTIL (62%, p<0.05). Independently, IM subtype and high sTIL subgroups achieved pCR at similar rates (62% and 76% respectively). We observed the largest difference in pCR rates between IM and non-IM subtype patients in the Moderate sTIL group. (58% vs 33%, p=0.051). Table: 98O
sTIL and pCR rates according to IM status
| IM | ||||
| sTIL Group | N | # pCR | %pCR | CI |
| Low | 3 | 1 | 33 | (0.01-0.91) |
| Moderate | 24 | 14 | 58 | (0.37-0.78) |
| High | 13 | 10 | 77 | (0.46-0.95) |
| Total | 40 | 25 | 62 | |
| Other Subtypes | ||||
| sTIL Group | N | # pCR | %pCR | CI |
| Low | 67 | 21 | 31 | (0.21-0.44) |
| Moderate | 66 | 22 | 33 | (0.22-0.46) |
| High | 8 | 6 | 75 | (0.35-0.97) |
| Total | 141 | 49 | 34 |
Conclusions
High TIL and IM subtype are associated with similar rates of pCR and the addition of the IM signature to sTIL high or sTIL low TNBCs did not impact prediction of pCR. In patients with moderate TIL, the IM subtype was associated with higher rates of pCR (58%) as compared to other subtypes (33%). Larger numbers of patients are needed to confirm the predictive value of the IM signature in TIL moderate TNBC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
MD Anderson Moon Shots Program, CPRIT Multi-Investigator Research Award (MIRA).
Disclosure
B. Lim: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen. B. Arun: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Invitae. S. Moulder: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.