Breast cancer therapy's leukemia risks.

Tamoxifen is not the only postsurgical therapy for breast cancer to pose some risk of fostering new cancers (SN: 4/2592, p. 259). However, few studies have attempted to quantify the long-term risks attributable to such adjuvant therapies. Now a trio of researchers with the National Cancer Institute in Bethesda, Md., have teamed with colleagues from seven other institutions to investigate leukemia risks associated with postsurgical treatments involving radiation, cell-killing drugs or both. Their finding: Such adjuvant therapies can augment a breast cancer patient's otherwise low risk of leukemia substantially -- up to 100 times.

The researchers identified 90 apparent leukemias among 82,700 women treated for invasive breast cancer between 1973 and 1985. They compared medical records of each of the 90 with records of two or three other breast cancer patients matched by age, ethnic background, year of diagnosis and years of follow-up.

On average, compared to women receiving no adjuvant therapy, women receiving radiation therapy had a 2.4-fold greater risk of leukemia, and those treated with "alkylating" chemotherapy drugs such as melphalan or cyclophosphamide had a 10-fold greater risk. The risks appear to be dose-dependent, however, report NCI's Rochelle E. Curtis and her coauthors in the June 25 NEW England Journal Of Medicine.

For instance, high doses of radiation alone (more than 9 grays) were linked with leukemia rates up to 10.4 times those seen in women receiving no adjuvant treatment. Similarly, high doses of melphalan (more than 350 milligrams) appeared to spike the incidence of leukemia to 100 times the rate in women receiving no adjuvant therapy. The new findings also confirm something observed in smaller studies -- that melphalan, seldom used anymore in adjuvant therapy, poses roughly 10 times the leukemia risk of cyclophosphamide. Even the low doses of cyclophosphamide typically used today (under 10,000 milligrams) roughly doubled leukemia risks in this study.

Perhaps most important, the researchers conclude, is the apparent synergistic risk of leukemia posed by mixing chemotherapy with high doses of radiotherapy to the bone marrow. This observation raises the possibility that the risks posed by adjuvant therapy may outweigh the advantages in patients over age 60 at low risk of recurrent breast cancer, notes I. Craig Henderson of the University of California, San Francisco, in an accompanying editorial.

In the same issue of the NEW ENGLAND Journal Of Medicine, researchers at the University of Texas Health Sciences Center in San Antonio review in detail the factors that signal a low risk of recurrent disease.