title: Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies.
abstract: BACKGROUND
  Breast cancer is composed of distinct subtypes defined mainly based on the expression of hormone receptors (HR) and HER2. For years, reproductive factors were shown to impact breast cancer risk but it is unclear whether this differs according to tumor subtype. In this meta-analysis we evaluated the association between parity, age at first birth, breastfeeding and the risk of developing breast cancer according to tumor subtype.
  
  
  METHODS
  PubMed and Embase were searched to identify epidemiological studies that evaluated the impact of parity and/or age at first birth and/or breastfeeding on breast cancer risk with available information on HR and HER2. Tumor subtypes were defined as: luminal (HR-positive, HER2-negative or HER2-positive), HER2 (HR-negative, HER2-positive) and triple-negative (HR-negative, HER2-negative). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. The MOOSE guidelines were applied.
  
  
  RESULTS
  This meta-analysis evaluated 15 studies, including 21,941 breast cancer patients and 864,177 controls. Parity was associated with a 25% reduced risk of developing luminal subtype (pOR 0.75; 95% CI, 0.70-0.81; p<0.0001). Advanced age at first birth was associated with an increased risk of developing luminal subtype (pOR 1.15; 95% CI, 1.00-1.32; p=0.05). Ever breastfeeding was associated with a reduced risk of developing both luminal (pOR 0.77; 95% CI, 0.66-0.88; p=0.003) and triple-negative (pOR 0.79, 95% CI, 0.66-0.94; p=0.01) subtypes.
  
  
  CONCLUSIONS
  The reproductive behaviors impact the risk of developing breast cancer but this varies according to subtype.
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.affiliation: Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, Belgium.
authors.forename: Bastien
authors.initials: B
authors.lastname: Nguyen
authors.affiliation: USC Oncologia Medica, Azienda Ospedaliera "Papa Giovanni XXIII", Bergamo, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Livraghi
authors.affiliation: Department of Internal Medicine, University of Genoa, Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ugolini
authors.affiliation: Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Fedro A
authors.initials: FA
authors.lastname: Peccatori
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, Belgium. Electronic address: hatemazim@icloud.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Azim
mesh_terms: D001942:Breast Feeding / Q000706:statistics & numerical data*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000378:metabolism; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D008423:Maternal Age; D010298:Parity; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D043762:Reproductive Behavior / Q000706:statistics & numerical data*; D017584:Reproductive History; D012307:Risk Factors; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Age at first birth; Breast cancer risk; Breast cancer subtypes; Breastfeeding; Parity