Predictors of HER2 FISH amplification in immunohistochemistry score 2+ infiltrating breast cancer:
Download
1 / 14

Predictors of HER2 FISH amplification in immunohistochemistry score 2 infiltrating breast cancer: a single institution - PowerPoint PPT Presentation


  • 424 Views
  • Uploaded on

Predictors of HER2 FISH amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Predictors of HER2 FISH amplification in immunohistochemistry score 2 infiltrating breast cancer: a single institution ' - arleen


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Slide1 l.jpg

Predictors of HER2 FISH amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis

Maria Vittoria Dieci1, Elena Barbieri1, Stefania Bettelli², Federico Piacentini1, Guido Ficarra², Sara Balduzzi1, Massimo Dominici1, PierFranco Conte1, Valentina Guarneri1

1Department of Oncology, Hematology and Respiratory Diseases, and ²Department of Pathology, University Hospital, Modena, Italy


Background l.jpg
Background immunohistochemistry score 2+ infiltrating breast cancer:

Herbst. Int J Radiat Oncol Biol Phys. 2004;59(suppl):21; Roskoski. Biochem Biophys Res Commun. 2004;319:1; Rowinsky. Annu Rev Med. 2004;55:433


Background cont d l.jpg
Background (cont’d) immunohistochemistry score 2+ infiltrating breast cancer:

  • HER2 amplification is the primary mechanism for overexpression

  • HER2 is amplified in 18-20% of infiltrating breast cancers

  • HER2 overexpression is associated with higher risk of recurrence and death, relative resistance to endocrine therapy, apparent lesser benefit from certain chemotherapeutic regimens

  • The MoAb antiHER2 Trastuzumab was FDA-approved in 1998 for treatment of metastatic disease

  • Adjuvant trastuzumab reduces the risk of recurrence and death by 1/2 and 1/3, respectively, in patients with early stage, high-risk HER2 positive breast cancers

  • One year trastuzumab costs: $70,000-$110,000


The need for accurate testing l.jpg
The Need For Accurate Testing immunohistochemistry score 2+ infiltrating breast cancer:

  • Various strategies to determine or confirm HER2 expression have been used in clinical trials

  • Correct HER2 assessment is critical for patients and clinicians since anti-HER2 therapies are effective in HER2+ disease only


Her2 expression l.jpg

Abnormal low immunohistochemistry score 2+ infiltrating breast cancer:

Abnormal high

amplification

amplification

HER2 expression

Normal 0

Normal 1+

Abnormal 2+

Abnormal 3+

Normal

Normal

IHC Images by Kornstein, MD, Medical College of Virginia


From fda to asco cap l.jpg
From FDA to ASCO/CAP immunohistochemistry score 2+ infiltrating breast cancer:

  • For IHC: the cut-off for 3+ score was raised from 10% to 30% of invasive tumor cells with uniform and intense membrane staining

  • For FISH amplification: a HER2/CEP17 ratio greater than 2.2, rather than equal or greater than 2.0

  • Recent studies have shown that the concordance between FISH and IHC is higher when the cut-off level to define HER2 3+ score is > 30%

As a consequence:

  • a higher proportion of breast cancer specimens are scored IHC 2+

  • but only 24% of the IHC 2+ tumors have gene amplification when tested by FISH

  • the request for FISH assay is increasing

Mass. Proc Am Soc Clin Oncol. 2000; Shah, Hum Pathol 2010


Endpoint l.jpg
Endpoint immunohistochemistry score 2+ infiltrating breast cancer:

To evaluate if routinely assessed pathologic parameters such as tumor grade, hormone receptor status and Ki67 are able to predict FISH results in patients with an equivocal IHC HER2 score 2+


Tissue specimens l.jpg
Tissue specimens immunohistochemistry score 2+ infiltrating breast cancer:

  • 480 infiltrating breast cancer with IHC 2+ and evaluable HER2/CEP17 ratio

    ANTIBODY: Novocastra Laboratories, clone CB11 until June 2008 and Ventana, clone 4B5 from July 2008

    PROBE: PathVysion HER-2 DNA Probe Kit (Vysis Inc., Downers Grove, IL)

    • 96% were primary surgical samples or core biopsy for patients undergoing neoadjuvant therapy

    • 4% were samples from bilateral breast cancer or metastases biopsy


Tumor characteristics l.jpg
Tumor characteristics immunohistochemistry score 2+ infiltrating breast cancer:


Distribution of fish results l.jpg
Distribution of FISH results immunohistochemistry score 2+ infiltrating breast cancer:


Distribution of fish results by g hr and ki67 asco cap criteria l.jpg
Distribution of FISH results by G, HR and Ki67 immunohistochemistry score 2+ infiltrating breast cancer: (ASCO/CAP criteria)


Distribution of fish results by g hr and ki67 fda criteria l.jpg
Distribution of FISH results by G, HR and Ki67 immunohistochemistry score 2+ infiltrating breast cancer: (FDA criteria)


Or for fish positive test asco cap and fda criteria l.jpg
OR for FISH positive test immunohistochemistry score 2+ infiltrating breast cancer: ASCO/CAP and FDA criteria


Discussion conclusions l.jpg
Discussion & Conclusions immunohistochemistry score 2+ infiltrating breast cancer:

  • While the association between HER2 status and pathological and molecular characteristics has been largely documented in literature, the possibility to predict HER2 amplification in HER2 equivocal (IHC 2+) cases has been less extensively studied

  • This is the largest single-institution series of HER2 IHC equivocal breast cancer specimens tested by FISH and analyzed to identify potential predictors for FISH amplification

  • This is the first report on the role of Ki67 index in such contest

  • On a series of 480 HER2 equivocal samples, both tumor grade and proliferation were found to be significantly associated with HER2 FISH amplification, according to the FDA and ASCO/CAP guidelines


ad