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  • br ACCEPTED MANUSCRIPT br population However the above

    2021-03-03


    ACCEPTED MANUSCRIPT
    population. However, the above-mentioned characteristics were included in multivariate analysis which confirmed the association of BMI≥25 and absence of HR N,N-Dimethylsphingosine as independent factor of early recurrence (hazard ratio: 1.79, 95% CI: 1.04-3.07, p=0.03).
    A particular interaction between host factors and tumor biology may then explain our results. HR-/HER2+ tumors may be more prone to an early systemic spread in response to metabolic alterations. More than estrogens, other mechanisms might be implicated as TGF-beta pathway (whose activation is proportionally related to BMI),22 angiogenesis23 and obesity-related markers of inflammation.24
    Conclusions
    Early recurrence rates of our study shed light on the impact of tumor biology in evaluating BMI as a prognostic factor in breast cancer. Due to the retrospective nature of the analysis and the small sample size, our findings are only provocative and hypothesis-generating and require further validation. However, patients’ baseline characteristics and treatment are very homogenous across investigated subgroups, strengthening our results.
    Although direct implications may not be inferred by our study, the lack of a reliable risk-profile assessment for HER2+ eBC patients, encourages further prospectively designed studies to further validate the surrogate relationship between BMI, HR expression and outcome.
    Trials should take into account these variables at a stratification level. In fact, if our data will be prospectively validated in larger cohorts, this might help clinicians to identify correct treatment and follow-up strategies in the controversial setting of anti-HER2 adjuvant therapies. We could hypothesize that HR-/BMI≥25 patients might benefit from escalation approaches, adding other anti-HER2 agents to standard Trastuzumab, while HR+/BMI<25 ones might be eligible for a shorter duration of treatment.
    Clinical Practice Points
    There is no evidence of reliable prognostic factors in the setting of HER2+ early breast cancer patients treated with adjuvant chemotherapy (CHT) and 1 year of Trastuzumab. A different pattern of recurrence has been observed according to hormone receptors’ (HRs) expression but host factors might also be involved in influencing patients’ outcome. Retrospectively collecting data from 238 women with stage I to III HER-2 positive BC who fully completed 1 year of treatment, we demonstrated that neither HRs alone nor BMI can predict 3 years distant disease-free survival. However, combining these two factors, our analysis showed that 3-years recurrence risk is higher for HR-/BMI≥25 patients compared to HR+/BMI<25. These results might help clinicians to identify correct treatment strategies. HR-/BMI≥25 patients might benefit from escalation approaches, adding other anti-HER2 agents to standard Trastuzumab, while HR+/BMI<25 ones might be eligible for a shorter duration of adjuvant treatment with anti HER-2 agents.
    Funding
    This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
    Ethical approval
    This article does not contain any studies with human participants or animals performed by any of the authors.
    References
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    11. Vaz-Luis I, Ottesen RA, Hughes ME, et al. Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res. 2012;14(5). doi:10.1186/bcr3324
    23. Chen J, Li T, Wu Y, et al. Prognostic significance of vascular endothelial growth factor expression in gastric
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    Tables
    Table 1. Baseline characteristics by hormonal receptor status (HR) and body mass index (BMI) category
    Variable HR+ pts HR- pts p* Variable BMI<25 pts BMI≥25 pts p* Total pts
    Menopausal status
    0,001 Menopausal status
    Post-
    Stage of disease
    0,11 Stage of disease
    I
    II
    III
    Undefined
    Lymph node status
    0,36 Lymph node status
    pN positive
    Tumor size (at diagnosis)
    Undefined
    Undefined
    Tumor histology
    0,33 Tumor histology
    carcinoma
    carcinoma
    Mixed
    Other
    Histologic grade
    Undefined
    Necrosis
    Yes
    No
    Undefined
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    PVI
    Intraductal carcinoma
    0,07 Intraductal
    carcinoma
    Adjuvant
    chemotherapy
    chemotherapy