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The prognostic value of Ki67 in systemically untreated patients with node-negative breast cancer
  1. Nirmala Pathmanathan1,2,3,
  2. Rosemary L Balleine3,4,5,6,
  3. Upali W Jayasinghe1,7,
  4. Kellie L Bilinski1,
  5. Pamela J Provan4,5,6,
  6. Karen Byth3,
  7. A Michael Bilous1,2,8,
  8. Elizabeth L Salisbury1,2,9,
  9. John Boyages1,10
  1. 1Westmead Breast Cancer Institute, Westmead Hospital, Westmead, New South Wales, Australia
  2. 2Department of Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, New South Wales, Australia
  3. 3Sydney Medical School, Westmead, University of Sydney, Sydney, New South Wales, Australia
  4. 4Translational Oncology, Western Sydney Local Health District, Sydney, New South Wales, Australia
  5. 5Westmead Institute for Cancer Research, Sydney, New South Wales, Australia
  6. 6Westmead Millennium Institute, NSW Australia, Sydney, New South Wales, Australia
  7. 7University of New South Wales, Sydney, New South Wales, Australia
  8. 8Department of Healthscope Pathology, Bella Vista, New South Wales, Australia
  9. 9Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia
  10. 10Macquarie University Cancer Institute, North Ryde, New South Wales, Australia
  1. Correspondence to Dr N Pathmanathan, Westmead Breast Cancer Institute, Westmead Hospital, Westmead, NSW 2145, Australia; Nirmala.Pathmanathan{at}bci.org.au

Abstract

Aim To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy.

Methods The cohort consisted of 203 cases treated with breast conserving surgery and radiation only; median follow-up was 183 months (range 156–277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour samples. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS).

Results Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a ‘Ki67-low’ (n=70) or ‘Ki67-high’ group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively.

Conclusions A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.

  • KI 67
  • Immunocytochemistry
  • Breast Cancer
  • Breast Pathology

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