Can some DCIS patients avoid adjuvant therapy? Still unknown.

A mong patients with ductal carcinoma in situ (DCIS), adjuvant treatment with radiation, tamoxifen, or both cuts the risk of later invasive disease in the affected breast by more than half compared with lumpectomy alone. And invasive disease in the same breast is associated with a higher risk of death, according to a study in this issue of the Journal. The new findings add to evidence that adjuvant treatments—because they reduce the risk of local recurrence—are warranted, said Irene Wapnir, M.D., lead author of the study and chief of breast surgery at Stanford University School of Medicine. The study also found that 35% of patients treated with lumpectomy alone—no adjuvant therapy—experienced a recurrence, in the form of either DCIS or invasive cancer. So for nearly two-thirds of 2,612 patients evaluated, adjuvant treatments were unnecessary, the authors conclude. That finding speaks to one of the most tenacious questions in DCIS treatment today: Which patients can avoid adjuvant therapy without risk of recurrence? “We’d like to get to the point that we can identify patients who can be treated only with lumpectomy and reserve radiation or tamoxifen for those who need it,” said Wapnir’s coauthor, James Dignam, Ph.D., an associate professor of biostatistics at the University of Chicago. But right now, we don’t know how to reliably identify those patients who can forgo adjuvant treatments.” This uncertainty has made the search for risk factors and prognostic markers that could help decide on follow-up to surgery a priority in DCIS research, but so far there have been few results. Stuart Schnitt, M.D., professor of pathology at Harvard Medical School, said the last decade has produced virtually no progress on tailored treatments for DCIS. That’s in part because scientists know so little about why, or whether, DCIS becomes invasive in the first place, he said. Ever since DCIS became widely diagnosed in the wake of mammography (it now accounts for about 25% of all breast cancer diagnoses), clinicians have opted to remove it surgically. Consequently, little is known about DCIS’ “natural history,” or how it might progress to cancer without treatment. “We’ve created a medical situation in which we immediately treat [DCIS] with the maximal therapy,” said Shelly Hwang, M.D., a professor of surgery at the University of California, San Francisco. “And that’s important because we often don’t know the biology of early diseases like DCIS; we think they’ll progress [to cancer], but not all of them go that way.” Hwang said researchers assume that DCIS will progress to cancer because both conditions share similar genetic and epigenetic changes in individual patients (although those similarities aren’t generalizable across the population). Fundamentally, DCIS is not invasive. “However, the assumption is that cancerous changes have occurred at the in situ stage and that progression to invasive cancer is likely,” she said. During the early 1980s, simple mastectomy was the treatment for most DCIS diagnoses. Now, treatment more commonly starts with image-guided needle biopsies followed by excision; lumpectomy; and, in up to a third of cases (mostly when tumors are diffused throughout the breast), mastectomy. How many patients receive adjuvant radiotherapy isn’t clear, although data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry suggest that it’s at least 50% in the United States. Adjuvant tamoxifen treatments aren’t as common, but they are increasing in many countries, according to Nina Bijker, M.D., Ph.D. a radiation oncologist at the Academic Medical Center in Amsterdam, The Netherlands.