Skip to main content

Advertisement

Log in

The identification of a small but significant subset of patients still targetable with anti-HER2 inhibitors when affected by triple negative breast carcinoma

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Triple (ER-, PR-, HER2-) negative breast carcinoma lack targeted therapies, making this group of tumors difficult to treat. By definition, the lack of HER2 expression means a case scoring 0 or 1+ after immunophenotypical analysis and makes the patients avoiding therapeutical chances with anti-HER2 inhibitors. We sought to recruit from a group of triple negative breast carcinoma, patients eligible for effective personalized targeted therapy with anti-HER therapies on the basis of their HER2 gene status.

Methods

135 patients diagnosed with IHC triple negative breast carcinoma were studied. Whole tissue sections were used for in situ hybridization analysis.

Results

8/100 (8 %) of ductal-type triple negative breast carcinoma presented Her-2/neu gene amplification versus 2/35 (5.7 %) non-ductal triple negative breast carcinoma. Three cases showed a ratio 2.5. One case showed Her-2/neu heterogeneous gene amplification, ratio 2.3. The other six showed from 7 to 8 absolute Her-2/neu gene copy number. Two cases staged pT1c, and eight cases staged pT2. Eight cases graded G3 and two cases G2.

Conclusion

(1) Eight percentage of ductal and 5.7 % non-ductal-type triple negative breast carcinoma present Her-2/neu gene amplification, (2) the standard diagnostic flowchart “do not FISH in 0–1+ (HER2-) breast carcinoma” should be replaced by “do FISH in triple (ER-, PR-, HER2-) negative breast carcinoma,” to avoid loss of therapeutical chances in a cohort of such a patients, (3) we demonstrated the identification of a small but significant subset of patients targetable with anti-HER2 inhibitors, giving patients affected by (ex)triple negative breast carcinoma new personalized therapeutical chances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Badve S, Dabbs DJ, Schnitt SJ, Baehner FL, Decker T et al (2011) Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol 24:157–167

    Article  PubMed  Google Scholar 

  • Bartlett JM, Ibrahim M, Jasani B, Morgan JM, Ellis I et al (2009) External quality assurance of HER2 FISH and ISH testing: 3 years of the UK national external quality assurance scheme. Am J Clin Pathol 131:106–111

    Article  PubMed  Google Scholar 

  • Bartlett JM, Starczynski J, Atkey N, Kay E, O’Grady A et al (2011) HER2 testing in the UK: recommendations for breast and gastric in situ hybridisation methods. J Clin Pathol 64:649–653

    Article  PubMed  CAS  Google Scholar 

  • Bloom KJ, Cote RJ (2011) Counterpoint: both immunohistochemistry and fluorescence in situ hybridization play important roles for HER2 evaluation. Clin Chem 57:983–985

    Article  PubMed  CAS  Google Scholar 

  • Brunelli M, Manfrin E, Martignoni G, Bersani S, Remo A et al (2008) HER-2/neu assessment in breast cancer using the original FDA and new ASCO/CAP guideline recommendations: impact on selecting patients for herceptin therapy. Am J Clin Pathol 129:907–911

    Article  PubMed  Google Scholar 

  • Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ et al (2012) TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol 30:2615–2623

    Article  PubMed  CAS  Google Scholar 

  • Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8:235–244

    Article  PubMed  Google Scholar 

  • Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S et al (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17:2639–2648

    PubMed  CAS  Google Scholar 

  • Crown J, O’Shaughnessy J, Gullo G (2012) Emerging targeted therapies in triple-negative breast cancer. Ann Oncol 23(Suppl 6):vi56–vi65

    Article  PubMed  Google Scholar 

  • Dendukuri N, Khetani K, McIsaac M, Brophy J (2007) Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis. CMAJ 176:1429–1434

    PubMed  Google Scholar 

  • Dowsett M, Bartlett J, Ellis IO, Salter J, Hills M et al (2003) Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres. J Pathol 199:418–423

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U et al (2009) Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol 27:2962–2969

    Article  PubMed  CAS  Google Scholar 

  • Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363:1938–1948

    Article  PubMed  CAS  Google Scholar 

  • Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N et al (2012) HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol 23:1371–1372

    Article  PubMed  CAS  Google Scholar 

  • Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358:1409–1411

    Article  PubMed  CAS  Google Scholar 

  • Pauletti G, Dandekar S, Rong H, Ramos L, Peng H et al (2000) Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol 18:3651–3664

    PubMed  CAS  Google Scholar 

  • Powell WC, Hicks DG, Prescott N, Tarr SM, Laniauskas S et al (2007) A new rabbit monoclonal antibody (4B5) for the immunohistochemical (IHC) determination of the HER2 status in breast cancer: comparison with CB11, fluorescence in situ hybridization (FISH), and interlaboratory reproducibility. Appl Immunohistochem Mol Morphol 15:94–102

    Article  PubMed  CAS  Google Scholar 

  • Reis-Filho JS, Tutt AN (2008) Triple negative tumours: a critical review. Histopathology 52:108–118

    Article  PubMed  CAS  Google Scholar 

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  PubMed  CAS  Google Scholar 

  • Starczynski J, Atkey N, Connelly Y, O’Grady T, Campbell FM et al (2012) HER2 gene amplification in breast cancer: a rogues’ gallery of challenging diagnostic cases: UKNEQAS interpretation guidelines and research recommendations. Am J Clin Pathol 137:595–605

    Article  PubMed  Google Scholar 

  • Vranic S, Teruya B, Repertinger S, Ulmer P, Hagenkord J, Gatalica Z (2011) Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17. Cancer 117:48–53

    Article  PubMed  Google Scholar 

  • Walker RA, Bartlett JM, Dowsett M, Ellis IO, Hanby AM et al (2008) HER2 testing in the UK: further update to recommendations. J Clin Pathol 61:818–824

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thanks Dr. Andrea Remo MD (Mater Salutis Hospital, Legnago, Verona) and Dr. Daniela Reghellin (Cazzavillan Hospital, Arzignano, Vicenza) for providing few material cases.

Conflict of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matteo Brunelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunello, E., Bogina, G., Bria, E. et al. The identification of a small but significant subset of patients still targetable with anti-HER2 inhibitors when affected by triple negative breast carcinoma. J Cancer Res Clin Oncol 139, 1563–1568 (2013). https://doi.org/10.1007/s00432-013-1479-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1479-0

Keywords

Navigation