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Track 1

DR LOVE: John, which chemotherapy regimen would you consider for this patient and would you offer her participation in the ALTTO trial (1.1)?

PROF CROWN: My belief is that this woman should receive TCH. I would not use an anthracycline in a 29-year-old who is likely to live long enough to possibly experience a delayed onset of cardiomyopathy, because I believe that we would be doing a disservice. The reasons include the approximate equivalence between TCH and the anthracycline-and trastuzumab-containing regimens in terms of the anticancer effect. I see “clear blue water” between the two regimens in terms of the occurrence of severe toxicities (Slamon 2006; [1.2]).

Under no circumstances would I allow her to join the ALTTO trial. Because the ALTTO trial mandates anthracycline-containing therapy, despite the efforts of some of us to allow a nonanthracycline-containing regimen, this woman would run the risk of receiving an anthracycline, trastuzumab and lapatinib.

DR LOVE: What about the possibility of her not receiving trastuzumab if she enrolled in the ALTTO trial?

PROF CROWN: I’d be comfortable with that. The data with lapatinib in metastatic disease are reassuring considering the extraordinarily difficult group in whom lapatinib was tested. Compared to patients in the pivotal trastuzumab trial who received first-line therapy with trastuzumab, lapatinib proved its mettle in patients whose disease was resistant to anthracyclines, taxanes and trastuzumab (Geyer 2006).

DR LOVE: Cliff, your group recently published results with dose-dense therapy in combination with trastuzumab (Dang 2008; [1.3]). Which chemotherapy regimen would you consider for this woman?

DR HUDIS: If she had an ejection fraction above 55 percent, I wouldn’t hesitate to use doxorubicin. Our series is far greater than what has been published so far. We have about 240 patients who have been treated on three consecutive prospective studies, and 100 percent of them have had pre-and post-AC ejection fractions measured. Notwithstanding the widely repeated notion of a five percent dropout rate after AC, no patients have failed to receive trastuzumab when they enrolled in these studies. We have one case of heart failure in the 240 patients and no long-term declines in ejection fraction to report.

Track 3

DR LOVE: Julie, would you offer zoledronic acid every six months to this young lady, as was done in the Austrian study recently reported at ASCO (Gnant 2008)?

DR GRALOW: In that trial, premenopausal women with ER-positive breast cancer received ovarian suppression for three years and were randomly assigned to also receive either tamoxifen or an aromatase inhibitor. It was a two-by-two study and the second randomization was zoledronic acid, four milligrams every six months for the three years, or not.

Previously, the Austrian Breast Cancer Study Group revealed that bone density was preserved with the addition of zoledronic acid in either arm — tamoxifen or an aromatase inhibitor. At ASCO 2008, they showed that there was no statistically significant difference in efficacy between tamoxifen and an aromatase inhibitor, combined with ovarian suppression.

The surprise was that the addition of zoledronic acid resulted in approximately a 35 percent reduction in recurrences.

I don’t think I would offer bisphosphonate therapy to this patient based on the Austrian trial, but I have two patients who mirror those in the study. However, I would offer this patient participation in the Intergroup trial, SWOG-S0307, which compares adjuvant clodronate versus ibandronate versus zoledronic acid.