Select Excerpts from the Breast Cancer Update Meet The Professors Session, held at the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005
On the third arm, all three agents were begun on day one. Six cycles of chemotherapy were given, and the trastuzumab was continued for one year. The intent of the trial was to see if the preclinical synergy seen between docetaxel, carboplatin and trastuzumab would be borne out in the adjuvant setting and whether we could avoid major problems with cardiotoxicity by eliminating the anthracycline.
The trial demonstrated that both the ACTH arm and the novel arm of TCH outperformed the control arm, with hazard ratios of 0.49 and 0.61, respectively. No statistically significant difference appeared between the two experimental arms.
In addition, the TCH arm had virtually no cardiotoxicity — only four out of more than 1,000 patients developed congestive heart failure.
DR LOVE: Could you comment on the TOPO II data?
DR MACKEY: The trial only allowed patients with HER2-positive disease identified by FISH. All of the tumor blocks were studied in two centers, so we were able to perform additional molecular analyses.
With HER2 amplification, a small strip of DNA is, by definition, amplified in this population; however, the HER2 amplicon can include the TOPO II gene, which is the target for anthracyclines.
Michael Press found that in about a third of patients, the HER2 amplicon included TOPO II (Press 2005). The really exciting finding was that the patients who had TOPO II amplification did very well if both targets, TOPO II and HER2, were hit by using an anthracycline and trastuzumab. In the two thirds of patients who did not have the amplified TOPO II, TCH performed just as well as the anthracycline-containing regimen and with no significant cardiotoxicity.
If we can validate this with additional follow-up, we may be able to select patients for an optimal adjuvant trastuzumab regimen on the basis of HER2 status in addition to TOPO II amplification by FISH, and these tests can be done simultaneously. If TOPO II is amplified, we might administer ACTH; however, if TOPO II is not amplified, those women could perhaps optimally be treated with TCH and not exposed to any significant risk of cardiotoxicity.
DR LOVE: Is TOPO II ready for “prime time?”
DR MACKEY: I don’t think so yet, although the data suggest we may finally have a third predictive assay in breast cancer. We have ER to tell us whether we should be using hormonal therapy, and we have HER2 to tell us whether we need trastuzumab. My prediction is that TOPO II amplification will become a validated predictive assay for benefit from anthracyclines, but we haven’t proved that yet.
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