BC friend recurred need links to articles...

[Soccermom]

need some info for friend that has been told that she may be able to be treated for recurrence to chest nodes (?) and wall with Herceptin. She is BRCA+, and was NOT her2 with her original diagnosis. Can anyone cite any studies regarding use of Herceptin in this case.

Thanks loads!
Marcia

[Bev]

I saw it yesterday but could not find. Herceptin seems to have similiar results for Her -. I'll go look in trash again. BB

[Bev]

The study was in Clinicalcareoptions.com this week. It's a continuing education credit site for docs. If you need log in or password data, let me know. Bev

[Soccermom]

Dear Bev, Thank you!
I Looked for the article but here are so many! Was the author Perez or Slamon? I do need a password and log in to access. Thanks again,Marcia

Are they saying that Herceptin is effective for Her2 negative cancers??? I do want to see that study!

[Bev]

Adjuvant Trastuzumab Benefit Seen in Both HER2-Positive and HER2-Negative Breast Cancers

Posting Date: June 08, 2007

• Retrospective laboratory analysis^[1]
  • National Surgical Adjuvant Breast and Bowel Project (NSABP) study B-31

Summary of Key Conclusions

• Clinical benefit of adjuvant trastuzumab seen consistently across all patient subsets defined by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC)
• Benefit from adjuvant trastuzumab possibly not limited to tumors defined as HER2 positive by current definitions
• Potential issues with HER2 status determination in adjuvant setting
  • HER2 expression may be a continuous variable; difficult to determine cutoff
  • Tumors with HER2/CEP17 ratio < 2 defined as HER2 negative, but can have HER2 expression
• Confirmatory studies needed

Background

• Treatment with trastuzumab indicated for patients with HER2-positive breast cancer
  • HER2 positive defined as
    • HER2 protein overexpression
      • 3+ staining by IHC
    • HER 2 gene amplification
      • HER2/CEP17 ratio > 2 by FISH
• Criteria for HER2 amplification/overexpression determined from advanced breast cancer patient population treated with trastuzumab
• Criteria not formally evaluated in breast cancer patients treated with trastuzumab in adjuvant setting
• Current study evaluated benefit of adjuvant trastuzumab on DFS according to HER2 status assessed by FISH and IHC in women enrolled on NSABP B-31
  • NSABP study B-31 interim report: May 2005^[2]

Summary of Study Design

[Bev]

Summary of Study Design

• Central laboratory analysis of HER2 amplification/overexpression
  • Samples with results by FISH: n = 1795
  • Samples with results by IHC: n = 1787
• HER2 status by FISH and IHC correlated with DFS events by treatment arm

Main Findings

• HER2 assessments showed high HER2 false-positive rate
  • 207 of 1795 cases (11.5%) HER2 negative by FISH
  • 299 of 1787 cases (16.7%) HER2 negative by IHC
  • 174 of 1795 cases (9.7%) HER2 negative by both FISH and IHC
• Trastuzumab associated with consistent benefit in DFS across all subsets defined by either FISH or IHC

[Bev]

<table class="ccotable" cellpadding="0" cellspacing="0" width="500"> <thead align="left"><tr><th>HER2 Assessment
</th> <th>

Patients, n

</th> <th colspan="2">

AC → P

</th> <th colspan="2">

AC → PT

</th> <th>

Risk Ratio
(95% CI)

</th> <th>

P Value

</th> </tr> <tr> <th>
</th> <th>
</th> <th>

n

</th> <th>

Events

</th> <th>

n

</th> <th>

Events

</th> <th>
</th> <th>
</th> </tr> </thead> <tbody> <tr> <td> FISH positive
</td> <td>

1588

</td> <td>

789

</td> <td>

160

</td> <td>

799

</td> <td>

85

</td> <td>

0.47
(0.36-0.61)

</td> <td>

< .0001

</td> </tr> <tr class="alternate"> <td> FISH negative
</td> <td>

207

</td> <td>

114

</td> <td>

23

</td> <td>

93

</td> <td>

8

</td> <td>

0.40
(0.18-0.89)

</td> <td>

.026

</td> </tr> <tr> <td> IHC positive (3+)
</td> <td>

1488

</td> <td>

740

</td> <td>

151

</td> <td>

748

</td> <td>

82

</td> <td>

0.48
(0.37-0.63)

</td> <td>

< .0001

</td> </tr> <tr class="alternate"> <td> IHC negative
(0, 1+, 2+)
</td> <td>

299

</td> <td>

161

</td> <td>

32

</td> <td>

138

</td> <td>

10

</td> <td>

0.32
(0.16-0.65)

</td> <td>

.0017

</td> </tr> <tr> <td> FISH and IHC negative
</td> <td>

174

</td> <td>

92

</td> <td>

20

</td> <td>

82

</td> <td>

7

</td> <td>

0.34
(0.14-0.80)

</td> <td>

.014

</td> </tr> </tbody> </table> AC → P; doxorubicin, cyclophosphamide followed by paclitaxel; AC → PT; doxorubicin, cyclophosphamide followed by trastuzumab and paclitaxel.

• No significant interaction between DFS benefit from trastuzumab and
  • HER2 protein level
  • HER2 gene copy number

References

1. Paik S, Kim C, Jeong J, et al. Benefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors: central testing results from NSABP B-31. Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Illinois. Abstract 511.
2. Romond E, Perez EA, Bryant J, et al. Docetaxel and cyclophosphamide followed by paclitaxel with or without trastuzumab as adjuvant therapy for patients with HER2-positive operative breast cancer: combined analysis of NSABP-B-31 and NCCTG-N9831. Program and abstracts of the 41st Annual Meeting of the American Society of Clinical Oncology; May 13-17, 2005; Orlando, Florida.

[Soccermom]

Thanks so much ,Bev!

[Adriana Mangus]

Just a question. Why did you get retested ror BRCA1,2. ?

I tested negative about 2 mos. Just wanted to know the need to get retested again. Thanks.

[Becky]

http://clinicaloptions.com/Oncology/...sules/511.aspx