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Prognostic molecular markers in women aged 35 years or younger with breast cancer: is there a difference from the older patients?
  1. Ching-Hung Lin1,
  2. Yen-Shen Lu1,2,
  3. Chiun-Sheng Huang3,
  4. Kuan-Ting Kuo4,
  5. Chung-Chieh Wang4,
  6. San-Lin You5,
  7. Po-Han Lin6,7,
  8. Dwan-Ying Chang1,
  9. Wen-Hung Kuo2,
  10. King-Jen Chang8,
  11. Ann-Lii Cheng1,2
  1. 1Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
  2. 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  3. 3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
  4. 4Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
  5. 5Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
  6. 6Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
  7. 7Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan
  8. 8Department of Surgery, Cheng Ching General Hospital, Taichung, Taiwan
  1. Correspondence to Professor Ann-Lii Cheng, Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei 10016, Taiwan; alcheng{at}ntu.edu.tw

Abstract

Background Women aged ≤35 years with breast cancer have a poor prognosis, but their prognostic factors have not been clearly defined.

Aims To evaluate whether the molecular markers used in age-unspecified breast cancer could also be applied to women ≤35 years.

Methods Archival tumours from patients aged ≤35 years with stage I–III breast cancer were collected. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki67 and P53 protein expression profiles in paraffin-embedded tissue sections were determined by immunohistochemistry. Tumours with an HER2 score of 2+ were further evaluated by fluorescence in situ hybridisation. Mutational analysis of exons 4–9 of the TP53 gene and exons 9 and 20 of the PIK3CA gene was carried out using direct sequencing analysis.

Results 116 patients with a median follow-up duration of 62.7 months were included. In addition to tumour size and axillary lymph node status, univariate analysis showed that high Ki67 expression, ER-negative, HER2 overexpression, and TP53 mutations were associated with shorter overall survival. Multivariate analysis showed that high Ki67 expression (HR=3.93, p=0.005), HER2 overexpression (HR=3.21, p=0.013) and TP53 mutations (HR=4.44, p=0.005) were associated with shorter overall survival. PR expression and PIK3CA mutations were not associated with survival.

Conclusions For women ≤35 years, TP53 mutations, Ki67 and HER2 expressions are strong prognostic factors. The limited prognostic value of hormone receptors suggests that the prognostic markers used in age-unspecified breast cancer may not be completely fit for this population.

  • Breast cancer
  • breast pathology
  • oncology
  • cancer genetics
  • cancer
  • cancer research
  • molecular genetics
  • molecular biology
  • breast
  • steroid receptors
  • colorectal cancer
  • gall bladder
  • oncogenes
  • P53
  • pancreas

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Footnotes

  • Funding The study was funded by the National Center of Excellence for Clinical Trials and Research of the National Taiwan University Hospital, Taipei, Taiwan (grant numbers DOH97-TD-B-111-001 and DOH99-TD-C-111- 001).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the institutional review board of the National Taiwan University Hospital (NTUH).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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