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Anthracyclines in early breast ca: Is the end near?

Anthracyclines in early breast ca: Is the end near?

SAN ANTONIO—Studies presented at the 2007 San Antonio Breast Cancer Symposium raise new questions about the role of anthracycline-based regimens as adjuvant therapy in early breast cancer, suggesting that these regimens may be appropriate only for a small subset of patients.

"The use of anthracyclines in the adjuvant treatment of all breast cancer patients is not supported by the existing data. Other approaches should now be adopted," said UCLA's Dennis Slamon, MD, PHD, who presented a new analysis of the phase III Breast Cancer International Research Group (BCIRG) 006 trial at the meeting (abstract 13).

His analysis showed that anthracyclines are beneficial only in patients with HER2-positive disease who also have amplification or overexpression of the topoisomerase II alpha (topo IIa) gene. Topo IIa amplification occurs only in about one-third of the HER2-positive patient population, or "a subset of a subclass," Dr. Slamon said.

Given that fact, he questioned the preferential use of anthracyclines in the HER2-negative population, which represents about 75% of all breast cancers.

And in the HER2-positive population, he said, "we now have trastuzumab [Herceptin] and lapatinib [Tykerb], one of which, thus far, appears to replace the gained efficacy of anthracyclines in patients with co-amplification of HER2 and topo IIa (about 8% of all breast cancers), without risking their known and well-established toxicities."

BCIRG 006 randomized 3,222 patients to doxorubicin/cyclophosphamide followed by docetaxel (Taxotere) (AC-T), to AC-T plus trastuzumab (AC-TH), or to an experimental non-anthracycline-based regimen of docetaxel, carboplatin, and trastuzumab (TCH).

The efficacy observed with AC-TH was restricted to patients with co-amplification of HER2 and topo IIa. In non-co-amplified patients, 4-year disease-free survival was 83% for AC-TH, 81% for TCH, and 71% for AC-T. But in co-amplified patients, disease-free survival was similar for all groups (83% to 85%). In other words, the inclusion of an anthracycline provided no additional benefit over the non-anthracycline-based TCH regimen.

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