title: An association study of established breast cancer reproductive and lifestyle risk factors with tumour subtype defined by the prognostic 70-gene expression signature (MammaPrint®).
abstract: Reproductive and lifestyle factors influence both breast cancer risk and prognosis; this might be through breast cancer subtype. Subtypes defined by immunohistochemical hormone receptor markers and gene expression signatures are used to predict prognosis of breast cancer patients based on their tumour biology. We investigated the association between established breast cancer risk factors and the 70-gene prognostication signature in breast cancer patients.
  
  
  
  Standardised questionnaires were used to obtain information on established risk factors of breast cancer from the Dutch patients of the MINDACT trial. Clinical-pathological and genomic information were obtained from the trial database. Logistic regression analyses were used to estimate the associations between lifestyle risk factors and tumour prognostic subtypes, measured by the 70-gene MammaPrint®signature (i.e. low-risk or high-risk tumours).
  
  
  
  Of the 1555 breast cancer patients included, 910 had low-risk and 645 had high-risk tumours. Current body mass index (BMI), age at menarche, age at first birth, age at menopause, hormonal contraceptive use and hormone replacement therapy use were not associated with MammaPrint®. In parous women, higher parity was associated with a lower risk (OR: 0.75, [95% confidence interval {CI}: 0.59-0.95] P = 0.018) and longer breastfeeding duration with a higher risk (OR: 1.03, [95% CI: 1.01-1.05] P = 0.005) of developing high-risk tumours; risk estimates were similar within oestrogen receptor-positive disease. After stratifying by menopausal status, the associations remained present in post-menopausal women.
  
  
  
  Using prognostic gene expression profiles, we have indications that specific reproductive factors may be associated with prognostic tumour subtypes beyond hormone receptor status.
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Makama
authors.affiliation: Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Albert Schweitzer Hospital, Department of Surgery, Dordrecht, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Drukker
authors.affiliation: Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: E J Th
authors.initials: EJT
authors.lastname: Rutgers
authors.affiliation: Department of Statistics, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Slaets
authors.affiliation: Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Rookus
authors.affiliation: Medical Department, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Tryfonidis
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Van't Veer
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: mk.schmidt@nki.nl.
authors.forename: M K
authors.initials: MK
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000209:etiology* / Q000503:physiopathology; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008019:Life Style; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D010298:Parity; D011247:Pregnancy; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D003278:Contraceptives, Oral, Hormonal; D011960:Receptors, Estrogen
keywords: 70-Gene signature; Breast cancer prognosis; Breast cancer risk factors; MammaPrint; Subtypes