Trastuzumab is active against the overexpressed HER2 oncogene in breast cancer, and four published prospective, randomised trials have shown that adjuvant trastuzumab substantially reduces rates of recurrence and death in patients with early-stage disease, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. A critical question is whether adjuvant anthracyclines are necessary for the treatment of HER2-positive breast cancer. The fifth prospective, randomised trial, the Breast Cancer International Research Group (BCIRG) 006 study evaluated the efficacy and safety of a
new nonanthracycline regimen with trastuzumab.

The study involved 3222 women with HER2-positive early-stage breast cancer who were randomised to one of flowing regimens:

• Doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T),

• AC-T plus 52 weeks of trastuzumab (AC-T plus trastuzumab)

• Docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH)

The primary study end point was disease-free survival. Secondary end points were overall survival and safety.

At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The following findings were reported:

• The estimated disease-free survival rates at 5 years were 75% in the AC-T, 84% in the AC-T plus trastuzumab, and 81% in the TCH groups.

• Estimated rates of overall survival were 87%, 92%, and 91%, in the above groups, respectively.

• There were no significant differences in efficacy (disease-free or overall survival) between the two trastuzumab regimens, whereas both were superior to AC-T.

• The rates of congestive heart failure and cardiac dysfunction were statistically significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (p<0.001).

• Eight cases of acute leukaemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.

The researchers conclude that that “addition of 1 year of adjuvant trastuzumab improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favoured the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukaemia.”

An accompanying editorial notes that the data from the BCIRG-006 study do not show the hoped-for superiority of the TCH regimen over the regimen of AC-T plus trastuzumab (and the study was not designed to show the noninferiority of TCH as compared with AC-T plus trastuzumab), thus these data do not clearly favour one regimen over the other. The authors discuss whether a risk-adapted approach be used to decide whether to use an anthracycline in adjuvant regimens for HER2-positive breast cancer? They conclude overall that the findings of the BCIRG-006 study suggest that a nonanthracycline regimen (TCH) is an acceptable standard of care.