For practical and economic reasons, we initially tested all tumor specimens from patients with invasive breast cancer utilizing the HercepTestTM. Then, if the tumors scored 2+, we automatically proceeded to testing by FISH based on the understanding that 12 percent of those specimens would be expected to have gene amplification.
One question that has been raised is, “Why not test everyone with FISH initially?” Because the great majority of tumor specimens are HER2-negative, we felt it was more practical to utilize the less expensive test initially. At the same time, in terms of the benefit from trastuzumab therapy, we realized that we don’t understand the real implications for patients with tumors that score 2+ on IHC and are FISH-positive.
Edith A Perez, MD
If one wants to know whether a patient has the HER2 alteration, one should do FISH testing. One should not do a default IHC and only if the tumor scores 2+, then do FISH. Using that algorithm, patients without the HER2 alteration will be treated with trastuzumab, and other patients with the HER2 alteration may not be treated.
The BCIRG trial we are conducting was designed with FISH as the only criteria for assessing HER2 status. I think the day when FISH testing is the only assay used in the community is coming, and I hope it will be sooner, rather than later.
Dennis Slamon, MD, PhD
Every patient with metastatic breast cancer in my practice has her tumor evaluated for HER2 gene amplification by FISH. Tumors with an IHC score of 3+ should be evaluated by FISH, because they may not have gene amplification. In those with an IHC score of 0 or 1+, 3 percent and 7 percent, respectively, will have HER2 gene amplification by FISH. We need to determine HER2 status accurately, because it is a matter of life or death.
Melody Cobleigh, MD
Tumors that score 2+ IHC are frequently found to be HER2-negative when tested by FISH. In those patients, I routinely have their tumors retested by FISH. On the other hand, I do not obtain a FISH analysis for tumors that score 3+ on IHC performed at a laboratory where I trust the pathologist.
Since HER2-positive breast cancer has a fairly specific phenotype (i.e., steroid receptor-negative, younger age, early relapse), I will retest those types of patients by FISH if I have a two- to three-year-old IHC score of 0 or 1+. If the patient’s tumor is IHC-negative and FISH-positive, I will treat them with trastuzumab despite the fact that we do not have clinical data for that group of patients. Tumors that are FISH-positive are likely to have ample amounts of HER2 receptors on their cell surface.
We lack quality control for both IHC and FISH. This is analogous to the situation encountered with estrogen receptor testing in the mid- to late 1970s. One wonders how many patients died because they did not receive adjuvant tamoxifen as a result of inadequate estrogen receptor testing. If adjuvant trastuzumab provides a benefit like adjuvant tamoxifen, we may encounter the same problem.
George Sledge, MD |
