Abstract
Background
Complex interactions between cancer and the immune system have an impact on disease
progression and therapeutic response. Our objective was to evaluate whether circulating
immune-related determinants are associated with pathological complete response (pCR)
in patients with locally advanced breast cancer (LABC) subjected to neoadjuvant chemotherapy
(NACT).
Patients and Methods
Luminex technology was used to profile 22 cytokines, 10 chemokines, FGF2, PDGF-BB,
VEGF, and Ca15-3/Ca125 glycoforms. Measurements were performed alongside standard
hematological determinations on pretreatment plasma samples from 151 patients including
41 cases with pCR assessed following RECIST criteria.
Results
Random Forest model analysis selected platelets, eotaxin, IFN-γ, IP10, and TGFβ2 as
significant predictors of pCR. These immune-related features were combined into a
quantitative score predictive of pCR. In patients who scored 0 or 1, none had pCR;
the pCR frequency increased in relation to the score value (23.5%, 41.2%, and 78.6%,
in score groups 2, 3, and 4, respectively). At multivariable logistic analysis, the
pCR score was highly significant (odds ratio = 3.15 per unit increment; CI: 1.85-5.38;
P < .0001); among clinical covariates (age, menopausal status, tumor stage, IHC subtype,
Ki-67, CA15.3, and CA125), only Ki-67 was statistically significant (P = .013).
Conclusion
This explorative study aimed to lay the conceptual and practical foundation that a
distinctive pattern of the immune determinant blood signature at diagnosis of LABC
significantly correlates with the patient's response to NACT and provides the groundwork
for larger studies that could lead to a minimally invasive tool for personalized medicine.
Keywords
Abbreviations:
BC (breast cancer), BMI (body max index), CI (confidence interval), ER (estrogen receptor), HER2 (human epidermal growth factor receptor 2), HR (hormonal receptors), IHC (immunohistochemistry), OR (odds ratio), pCR (pathological complete response), PR (progesterone receptor), RECIST (Response Evaluation Criteria in Solid Tumors), TNBC (triple negative breast cancer)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: May 23, 2022
Accepted:
May 19,
2022
Received in revised form:
May 2,
2022
Received:
October 29,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
