[Lani]

Patricia--where are you located? I just posted on this forum that a kit has been approved in Canada (don't know who is using it yet, if anyone) which allows injection of a radionucleide --similar to the radioactive glucose used for the PET scans--which pairs radioactive Indium with hercept(fused together). This shoud allow detection of minimal residual disease which is her2+ as well as allowing better margins to be obtained with surgery of her2+ tumors)

I copy it again here--it is hot off the press in Jan 2011 journal although epublished Sept 1 2010!!

: Nucl Med Biol. 2011 Jan;38(1):129-36. Epub 2010 Sep 1.
A kit to prepare (111)In-DTPA-trastuzumab (Herceptin) Fab fragments injection under GMP conditions for imaging or radioimmunoguided surgery of HER2-positive breast cancer.
Scollard DA, Chan C, Holloway CM, Reilly RM.

Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada M5S 3M2.
Abstract
INTRODUCTION: The human epidermal growth factor receptor-2 (HER2) gene is amplified in 25% of invasive breast cancers, and receptor overexpression has been noted in up to 60% of early stages of the disease [ductal carcinoma in situ (DCIS)]. Preclinical studies have revealed high tumor/blood ratios (>27:1) for (111)In-labeled Fab fragments of the HER2 monoclonal antibody, trastuzumab (Herceptin) ((111)In-DTPA-trastuzumab Fab) at 72 h pi in athymic mice bearing subcutaneous human breast cancer xenografts. Our aim in this study was to formulate a kit for preparation of (111)In-DTPA-trastuzumab Fab injection under good manufacturing practice (GMP) conditions suitable for human administration in a Phase I clinical trial of imaging and radioimmunoguided surgery (RIGS) of HER2-positive breast cancer.

METHODS: Fab fragments were produced by digestion of trastuzumab IgG (Herceptin) with immobilized papain for 20 h at 37°C. Fab fragments were purified by ultrafiltration, then reacted with a 10-fold molar excess of diethylenetriaminepentaacetic acid (DTPA) dianhydride. DTPA-Fab fragments were purified, then sterilized by filtration into unit dose glass vials (kits). Kits were tested against specifications for volume (0.9-1.1 ml), protein concentration (0.45-0.55 mg/ml), pH (5.5-6.5), DTPA substitution (0.5-4.0 mol DTPA/mol Fab), appearance (clear, colorless and particle free), labeling efficiency (≥85%), and sterility and apyrogenicity (USP XXXII). Immunoreactivity of (111)In-DTPA-trastuzumab Fab towards HER2 was measured by saturation radioligand binding assays using SKBR-3 human breast cancer cells (specifications: K(a)=0.6-9.6×10(7) L/mol; B(max)=0.6-10.4×10(6) sites/cell). (111)In-DTPA-trastuzumab Fab injection was prepared by adding 80-100 MBq of (111)InCl(3) to a single kit vial and incubating for 30 min at room temperature. (111)In-DTPA-trastuzumab Fab was assayed for the amount of radioactivity and tested for pH, radiochemical purity (RCP), appearance and sterility.

RESULTS: Pure and homogeneous Fab fragments were produced. Eleven lots of kits met established quality specifications. The labeling efficiency with (111)In was 90.6±2.2%. (111)In-DTPA-trastuzumab Fab bound specifically to HER2 on SKBR-3 cells (K(a)=4.8±2.5×10(7) L/mol and B(max)=1.6±0.8×10(6) sites/cell). Thirteen lots of (111)In-DTPA-trastuzumab injection met all established specifications. Kits were stable for 90 days and (111)In-DTPA-trastuzumab Fab injection was stable for 24 h stored at 4°C.

CONCLUSIONS: A kit was formulated under GMP conditions for the preparation of (111)In-DTPA-trastuzumab Fab injection suitable for human administration. The kits were approved by Health Canada.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21220136 [

You might consider sending your most recent slides to another institution for her2 testing--MDA Anderson and Stanford, among others offer this service.

Some test + by CISH but not by FISH . It sounds like your testing was by IHC (where results are +,++ or+++. FISH results come in numbers. You can google Entrez PUBMED and put her2 testing into the subject line and look at the abstracts (and open articles) on her2 testing.

Perhaps a serum her2 test might help clear things up (available from Quest and other major labs) and/or testing for CTCs(which can be tested to see if they are her2+--at least by some labs at Dana Farber and by the lab of Stephanie Jeffries at Stanford but not available from normal clinical labs) would help tell whether there still are her2+ tumor cells in your body that need herceptin to which something else can be added.

The true and accurate makeup of your new tumor is most important and from what I have learned at conferences would warrants a second opinion. Her2 testing is notoriously difficult.

Where on your arm was the lesion? Was it in the skin vs bone vs between the two?

When you say it was not her2+ (fully cancerous) what do you mean?

Can you get/post the pathology report? Could the lesion on your arm have been something other than breast cancer?

I would be happy to post any research results, but need to know more about what this new lesion was and why they think it was related to your breast cancer but not her2 +.

They have found that those Stage IVs who are on herceptin can have all sorts of different kinds of ctcs(circulating tumor cells) floating around in their circulation--including triple negative. But we don't know enough yet to treat based on CTCs. Bone marrows seem to be better at looking for residual disease and its makeup, but are yet standard of care (and unlikely to be as most oncologists I ask reluctantly admit that they do not like doing them--it is not the patients who complain!)

If your arm lesion was in the bone and the got bone biopsies--those could be used to guide what to add to your treatment as I understand it--if all other indications showed your breast cancer remained her2+.

Please try to get additional information as you would have a totally different problem if you had a superficial melanoma of the skin of the arm than if you had a bone metastasis from a breast cancer which was no longer her2+

I am in no way qualified to give any advice, but will try to research to get you the information to enable you ask the best questions.

Hope some of this helps!Good luck