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Breast Cancer

, Volume 25, Issue 4, pp 416–430 | Cite as

Clinical utility of RT-PCR in assessing HER 2 gene expression versus traditional IHC and FISH in breast cancer patients

  • Moushumi Suryavanshi
  • Anurag Mehta
  • Jiten Jaipuria
  • Dushyant Kumar
  • Gayatri Vishwakarma
  • Manoj Kumar Panigrahi
  • Haristuti Verma
  • Mumtaz Saifi
  • Sanjeev Sharma
  • Simran Tandon
  • D. C. Doval
  • Bhudev C. Das
Original Article
  • 93 Downloads

Abstract

Background

IHC and FISH are used for categorizing HER 2 status in breast cancer at the protein and DNA level, respectively. HER 2 expression at the RNA level is quantitative, cheaper, easier to standardize and free from interobserver variation.

Methods

115 consecutive patients were tested by IHC, FISH and RT-PCR (test cohort). Assuming FISH result to be the response variable, ROC curves for RT-PCR ratio were analyzed to label HER 2 negative, equivocal and positive cases as RT-PCR score 1, 2 and 3, respectively. Inter-relationships between RT-PCR, IHC and FISH were defined. ‘Clinical benefit’ of a test was defined as proportion of patients labeled unequivocally as HER 2 positive or negative. Population for 1 year was simulated constraint to previous reports of HER 2 positivity and IHC category distribution by a meta-analysis of previous studies that evaluated concordance between IHC and FISH to determine HER 2 status (simulation cohort). Four diagnostic pathways in the simulation cohort were defined—(1) initial IHC, followed by FISH (conventional pathway); (2) initial RT-PCR, followed by FISH; (3) initial IHC, followed by RT-PCR and then by FISH; (4) initial RT-PCR, followed by IHC and then by FISH. The clinical benefit of IHC and RT-PCR in the four pathways was analyzed and sensitivity analysis for incremental cost-effectiveness ratio and cost–benefit comapring RT-PCR against IHC, both as first-line tests and among those with IHC score 2 as a reflex second-line test was performed by the Monte Carlo technique.

Findings

115 patients comprised the study population. While none with IHC score of 0 or 1 was FISH positive for HER 2, all cases with IHC score of 3 were FISH positive. 43 cases were assigned IHC score of 2. Thus, 72 patients benefited from the initial IHC testing [clinical benefit 62.6%], with the overall concordance between IHC and FISH being 100% for those with IHC score of 0, 1 and 3 (conclusive IHC categories). For RT-PCR with 100% concordance, 15.7% (115–97 = 18) patients would have benefited from RT-PCR testing if it was used as a first-line test. If RT-PCR would have been used as a second-line test among those with IHC score 2 (n = 43), then only 6 patients would have been assigned a conclusive RT-PCR category (category 1 or 3) translating to a clinical benefit of 14% (6/43) as a second-line test. As a second-line test it had 51% probability to prove more cost-effective than the conventional pathway, provided the cost of RT-PCR was 0.4 times the cost of IHC. Also in a three-step pathway, RT-PCR upfront would have 56% probability of higher cost–benefit provided the cost of RT-PCR was 0.1 times the cost of IHC.

Conclusion

RT-PCR results were found to be suboptimal to IHC in terms of discriminative ability and clinical benefit; thus, it is unlikely to replace IHC as a first-line test in the near future.

Keywords

HER 2 RT-PCR Breast cancer Clinical benefit 

Notes

Author contribution

All authors equally contributed to manuscript designing, analysis and editing.

Funding

Institutional funded study.

Compliance with ethical standards

Conflict of interest

The authors declare that they do not have any conflict of interest.

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Copyright information

© The Japanese Breast Cancer Society 2018

Authors and Affiliations

  • Moushumi Suryavanshi
    • 1
  • Anurag Mehta
    • 2
  • Jiten Jaipuria
    • 3
  • Dushyant Kumar
    • 1
  • Gayatri Vishwakarma
    • 4
  • Manoj Kumar Panigrahi
    • 1
  • Haristuti Verma
    • 1
  • Mumtaz Saifi
    • 1
  • Sanjeev Sharma
    • 1
  • Simran Tandon
    • 5
  • D. C. Doval
    • 6
  • Bhudev C. Das
    • 5
  1. 1.Centre for Molecular Diagnostic and Cell BiologyRajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia
  2. 2.Lab Services, Blood Transfusion & MolecularRajiv Gandhi Cancer Institute and research CentreNew DelhiIndia
  3. 3.Department of UrogynaeoncologyRajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia
  4. 4.Department of ResearchRajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia
  5. 5.Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR) Amity UniversityNoidaIndia
  6. 6.Medical OncologyRajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia

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