title: Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013.
abstract: BACKGROUND
  The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the 'Luminal A-like' and 'Luminal B-like (HER2-negative)' subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined.
  
  
  METHODS
  Six hundred seventy-one patients (≥35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included.
  
  
  RESULTS
  'Luminal A-like' tumors were mostly G1 or G2 (90%) whereas 'Luminal B-like' tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In 'Luminal B-like' tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 'Luminal A-like' tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively.
  
  
  CONCLUSIONS
  Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of 'Luminal A-like', while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of 'Luminal B-like', when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.|b Department of Pathology and Cytology , Blekinge County Hospital , Karlskrona , Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehinger
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.|c Department of Oncology , Skåne University Hospital , Lund , Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Malmström
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.affiliation: d Department of Histopathology , Nottingham University Hospitals NHS Trust , Nottingham , UK.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Elston
authors.affiliation: e Department of Surgery , Helsingborg Hospital , Helsingborg , Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Falck
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Forsare
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.|f Department of Pathology , Skåne University Hospital , Lund , Sweden.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.affiliation: g Division of Surgery, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.|h Department of Surgery , Skåne University Hospital , Lund , Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: i Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences , Linköping University , Linköping , Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.affiliation: a Division of Oncology and Pathology, Department of Clinical Sciences , Lund Cancer Center at Medicon Village, Lund University , Lund , Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone