{
  "abstract": "Aims Breast cancer (BC) during pregnancy (PrBC) and the postpartum period (PPBC) often exhibits more aggressive tumour characteristics and is associated with a poorer prognosis compared with age-matched nonpregnant patients with BC. The underlying mechanisms for this increased aggressiveness remain unresolved. Intratumoral hypoxia, a known adverse prognostic marker in nonpregnant BC, has not yet been studied in PrBC/PPBC. This is particularly intriguing due to the potential exposure to angiogenesis-stimulating factors during pregnancy, which may influence tumour behaviour.Methods Tumour tissues from 148 patients with PrBC and 45 patients with PPBC were used to create a tissue microarray (TMA), and clinical and outcome data were obtained. The TMAs were stained for hypoxia-associated protein markers: glucose transporter-1, carbonic anhydrase IX and hypoxia-inducible factor-1α.Results Of all 193 tumours, 152 (79%) expressed at least one of these proteins indicative of intratumoral hypoxia. The presence of intratumoral hypoxia was associated with a higher histological grade (83% grade III vs 63%) and frequent hormone receptor negativity (68% vs 39%). In a multivariable analysis, the presence of intratumoral hypoxia indicated a significantly worse prognosis (HR 2.532, 95% CI 1.1 to 5.7) for patients with PrBC and PPBC.Conclusion This unique study, the first in patients with PrBC and PPBC, showed that, despite their likely exposure to angiogenesis-stimulating factors, intratumoral hypoxia is frequent and affects 79% of patients. Importantly, patients with tumours overexpressing hypoxia markers have significantly worse survival. This suggests that hypoxia may be an important mechanism in carcinogenesis and clinical behaviour of PrBC and PPBC.",
  "authors": [
    {
      "affiliations": [
        "Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands",
        "Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Carsten F J Bakhuis"
    },
    {
      "affiliations": [
        "Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Paul J van Diest"
    },
    {
      "affiliations": [
        "Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Britt B M Suelmann"
    },
    {
      "affiliations": [
        "Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Natalie D ter Hoeve"
    },
    {
      "affiliations": [
        "Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Sven van Kempen"
    },
    {
      "affiliations": [
        "Pathology, PALDordrecht, Dordrecht, The Netherlands"
      ],
      "name": "Pieter J Westenend"
    },
    {
      "affiliations": [
        "Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands"
      ],
      "name": "Sabine C Linn"
    },
    {
      "affiliations": [
        "Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Elsken van der Wall"
    },
    {
      "affiliations": [
        "Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Carmen van Dooijeweert"
    }
  ],
  "title": "Prognostic value of immunohistochemical markers of intratumoral hypoxia in pregnancy-associated breast cancer",
  "uid": "acfd629e-c1e3-5ca3-a132-d5c2450f5ba5"
}