title: Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients.
abstract: OBJECTIVE
  To evaluate the long-term prognostic impact of age, local treatment and intrinsic subtypes on the risk of local-regional recurrence (LRR) and breast cancer mortality among low-risk patients.
  
  
  METHODS
  Cohort study with prospectively collected data, balanced five-year age groups, including 514 Danish lymph node negative breast cancer patients diagnosed between 1989 and 1998, treated with mastectomy (N = 320) or breast-conserving therapy (BCT) (N = 194) and without systemic treatment. Intrinsic subtype approximation was performed by combining information on estrogen-, progesterone-, HER2 receptor and Ki67.
  
  
  RESULTS
  The majority of the tumors had a luminal subtype: 70% Luminal-A (LumA), 16% Luminal-B (LumB), and 10% Luminal-HER2 + (Lum-HER2+). The distribution of intrinsic subtypes between younger (≤45 years) and older (>45 years) patients was similar. Intrinsic subtypes had no prognostic impact on the 20-year LRR risk, regardless of age. A distinct 20-year mortality pattern was observed among the younger patients: 11% of patients with LumB tumor died of breast cancer within the first five years after primary surgery, 23% of patients with Lum-HER2+ tumor died within a 5-10-year period, whereas patients with LumA tumor died with a constant low rate throughout the 20-year period. After 20 years of follow-up, patients with LumA tumor had breast cancer mortality comparable to that of patients with LumB tumor (20%) and lower than Lum-HER2+ tumor (39%). Among the older patients, no distinct mortality pattern was observed, and the 20-year breast cancer mortality was not associated with intrinsic subtypes.
  
  
  CONCLUSIONS
  Among low-risk patients, 96% of the tumors were Luminal and the distribution of intrinsic subtypes between younger (≤45 years) and older (>45 years) patients was similar. The observed higher frequency of LRR among younger low-risk BCT patients was not associated intrinsic subtype. The 20-year breast cancer mortality was non-significant for LumA tumors among the older patients, whereas among the younger patients, LumA tumors had a comparable mortality with LumB, but lower than for Lum-HER2 + tumors.
authors.affiliation: a Department of Experimental Clinical Oncology , Aarhus University Hospital , Denmark.|b Department of Pathology , Aarhus University Hospital , Denmark.
authors.forename: Tinne
authors.initials: T
authors.lastname: Laurberg
authors.affiliation: a Department of Experimental Clinical Oncology , Aarhus University Hospital , Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.affiliation: b Department of Pathology , Aarhus University Hospital , Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Tramm
authors.affiliation: b Department of Pathology , Aarhus University Hospital , Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Jensen
authors.affiliation: a Department of Experimental Clinical Oncology , Aarhus University Hospital , Denmark.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Lyngholm
authors.affiliation: c Breast Surgery Unit , Aarhus University Hospital/Randers Regional Hospital , Denmark.
authors.forename: Peer M
authors.initials: PM
authors.lastname: Christiansen
authors.affiliation: a Department of Experimental Clinical Oncology , Aarhus University Hospital , Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008408:Mastectomy / Q000401:mortality*; D015412:Mastectomy, Segmental / Q000401:mortality*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000401:mortality*; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone