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Plasma Profile of Immune Determinants Predicts Pathological Complete Response in Locally Advanced Breast Cancer Patients: A Pilot Study

  • Author Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Rosalba Miceli
    Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Affiliations
    Clinical Epidemiology and Trial Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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  • Author Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Chunmei Cao
    Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Affiliations
    Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
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  • Nicolai N. Maolanon
    Affiliations
    Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China

    Department of Chemistry, University of Copenhagen, Copenhagen, Denmark
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  • Roland Jacobs
    Affiliations
    Department of Rheumatology and Clinical Immunology, Hannover Medical School, Hannover, Germany
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  • Author Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Jiong Wu
    Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Affiliations
    Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
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  • Author Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Rosaria Orlandi
    Correspondence
    Address for correspondence: Rosaria Orlandi, Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy
    Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.
    Affiliations
    Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
    Search for articles by this author
  • Author Footnotes
    # R.M., C.C., J.W., and R.O. contributed equally to this study.

      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)
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