Abstract 205P
Background
Recent evidence suggests that chemotherapy (CT) efficacy relies in part on the capacity of chemotherapeutic agents to interact with the immune system. CT can induce various tumor cell death modalities processed by immune cells, resulting in their activation and induction of antitumor immunity. Long-term effects of conventional CT may be attributed to the stimulation of immunological responses.
Methods
Prospective observational study carried out in the University General Hospital of Valencia in early triple-negative breast cancer patients. Blood tests were performed at the beginning and at the end of the neoadjuvant chemotherapy (NACT) treatment. Soluble mediators in peripheral blood (immune biomarkers) were analyzed using a preconfigured panel based on Luminex xMAP technology.
Results
21 patients were evaluated (mean age 55 years, 100% females). 19% stage I-B, 52.4% stage II-A/B, 28.6% stage III-B/C (8a AJCC edition). 71.4% had EGFR expression and two patients were BRCA1 mutated. NACT was administered in all patients using schemes with taxanes; carboplatin was added in half of the patients. Baseline median plasma levels of soluble biomarkers are shown in the table. Table: 205P
Soluble biomarkers | Median plasma leveles (pg/ml) |
sPD-1 | 2745 |
sPD-L1 | 803 |
sPD-L2 | 9779 |
sCTLA-4 | 90 |
sLAG3 | 270,771 |
sCD27 | 1381 |
sCD28 | 6325 |
sCD80B7 | 766 |
sICOS | 4596 |
It was significantly observed that patients with lower levels of sPD-1 (<920 pg/ml), sCTLA-4 (<34 pg/ml) and sLAG3 (< 190575 pg/ml), have greater rates of pathological complete response (pCR) than those with higher levels. Moreover, lower levels of sPD-1 (<362 pg/ml) was correlated with patients without lymph node involvement.
Conclusions
Higher levels of sPD-1, sCTLA-4 and sLAG3 at the beginning of NACT can predict a worse response to chemotherapy compared to low levels of these biomarkers. This shows a way to investigate therapies including neoadjuvant immunotherapy that can reverse this resistance to NACT in this subgroup of patients. This fact reveals the importance of the immunomodulation role of chemotherapy in early triple-negative breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Molecular Oncology Laboratory, FIHGUV. Medical Oncology, University General Hospital of Valencia.
Funding
CB16/12/00350 from ISCIII and AMACMA. STM is funded by a Scholarship from Generalitat Valenciana (ACIF /2018/275).
Disclosure
All authors have declared no conflicts of interest.