title: Invasive lobular carcinoma of the breast: long-term prognostic value of Ki67 and histological grade, alone and in combination with estrogen receptor.
abstract: BACKGROUND
  The aim of the present study was to investigate the long-term impact of prognostic factors in invasive lobular carcinoma (ILC) of the breast, with a primary focus on Ki67 and histological grade, alone and in combination with estrogen receptor (ER).
  
  
  METHODS
  One hundred and ninety two well-characterised patients with ILC were included in the study. Ki67, histological grade and ER were evaluated and combined into a prognostic index (KiGE). All grade 1 tumours and ER-positive (ER+) grade 2 tumours with Ki67 ≤ 30% were classified as low-KiGE and all the others as high-KiGE.
  
  
  RESULTS
  Overall, 31% of the patients have died from breast cancer. The median follow-up of the patients still alive was 21 years. Age, tumour size, axillary lymph node status (nodal status), histological grade, Ki67 and KiGE were significant prognostic factors for breast cancer mortality (BCM) in univariable analysis. In a multivariable model, adjusted for adjuvant treatment, age and progesterone receptor (PgR), the strongest prognostic factors for BCM were: Nodal status (hazard ratio (HR) = 2.9, 95% confidence interval (95% CI): 1.4-6.1), KiGE (HR = 2.0, 95% CI: 1.1-3.6), and tumour size (HR = 1.9, 95% CI: 0.98-3.8). By combining these three factors, 37% of the ILC's could be further divided into a low-risk group, consisting of node negative small (≤ 20 mm) low-KiGE tumours, with a BCM of 5% (95% CI: 1-13%) at 10 years and 12% (95% CI: 5-22%) at 20 years follow-up. None of these patients recieved chemotherapy and only 2 recieved endocrine treatment with tamoxifen.
  
  
  CONCLUSIONS
  The combination of Ki67, histological grade and ER into KiGE, together with tumour size and nodal status make it possible to identify a large group of ILC patients with such a good long-term prognosis that chemotherapy can be safely avoided and exclusion of endocrine therapy considered.
authors.affiliation: Department of Clinical Sciences, Division of Oncology, Skåne University Hospital, Lund University, SE-221 85 Lund, Sweden ; Department of Oncology, Växjö Central Hospital, SE-351 85 Växjö, Sweden.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Narbe
authors.affiliation: Department of Clinical Sciences, Division of Oncology, Skåne University Hospital, Lund University, SE-221 85 Lund, Sweden.
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.affiliation: Division of Pathology, SE-221 85 Lund, Sweden.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.affiliation: Division of Surgery, Clinical Sciences, SE-221 85 Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Division of Surgery, Clinical Sciences, SE-221 85 Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Department of Clinical Sciences, Division of Oncology, Skåne University Hospital, Lund University, SE-221 85 Lund, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
keywords: Breast cancer; Histological grade; Invasive lobular carcinoma; Ki67; Prognostic factors