Growth fraction as a predictor of response to chemotherapy in node-negative breast cancer

Authors

  • Mohammed A. Aleskandarany,

    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
    2. Pathology Department, Faculty of Medicine, Menoufyia University, Menoufyia, Egypt
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  • Andrew R. Green,

    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
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  • Emad A. Rakha,

    1. Pathology Department, Faculty of Medicine, Menoufyia University, Menoufyia, Egypt
    2. Department of Pathology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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  • Rabab A. Mohammed,

    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
    2. Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
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  • Somaia E. Elsheikh,

    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
    2. Pathology Department, Faculty of Medicine, Menoufyia University, Menoufyia, Egypt
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  • Desmond G. Powe,

    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
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  • Emma C. Paish,

    1. Department of Pathology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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  • R. Douglas Macmillan,

    1. The Breast Unit, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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  • Steve Chan,

    1. Department of Oncology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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  • Samreen I. Ahmed,

    1. Department of Oncology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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  • Ian O. Ellis

    Corresponding author
    1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
    • Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, University of Nottingham, Hucknall Road, Nottingham NG5 1PB, United Kingdom
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    • Fax: +44-0115-9627768


Abstract

Accurate predictive markers of chemotherapeutic response in early breast cancer are still lacking. The role of tumour growth fraction as a predictor of response to chemotherapy was assessed in early breast cancer. In this study, immunohistochemical expression of MIB1 was studied in a well-characterised series of early (Stages I and II) node-negative breast carcinoma cases (n = 100) with long-term follow-up that have received adjuvant chemotherapy (cyclophosphamide/methotrexate/5-fluorouracil regimen). In addition, 728 cases who did not receive adjuvant chemotherapy were used as a control group. Increased tumour growth fraction was associated with a better response to adjuvant chemotherapy in terms of longer breast cancer specific survival and disease-free interval [hazard ratio (HR) = 0.354, 95% CI = 0.177–0.688, p = 0.003 and HR = 0.396, 95% CI = 0.205–0.768, p = 0.006, respectively]. In contrast to the control group, patients with high growth fraction tumour (>70%) showed an excellent outcome with infrequently reported events during the period of follow-up. Importantly, patients with a low growth fraction (≤10%) showed frequent recurrences and shorter survival time with outcome comparable to those of high growth fraction who did not receive chemotherapy. Therefore, tumour growth fraction can be used to assign patients into distinct groups showing differential response to adjuvant chemotherapy. Patients with a high growth fraction appear to be ideal candidates for adjuvant chemotherapy while those with low growth fraction are less likely to benefit and are prone to the potential serious side effects of adjuvant chemotherapy.

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