Tuma, Rabiya S. PHD
SAN FRANCISCO—Women under age 45 treated for ductal carcinoma in situ (DCIS) with lumpectomy and radiation have a significantly higher risk of local recurrence compared with women 45 to 50 years of age at diagnosis, according to a study reported here at the 2009 Breast Cancer Symposium.
“Our preliminary data suggest that younger women may have a higher risk of recurrence following lumpectomy and radiation,” said Iwa Kong, MD, a fellow in the Department of Radiation Oncology at Sunnybrook Health Sciences Centre and the University of Toronto, who presented the data. “And this risk is almost double that of older women. Our data do not imply that young women require mastectomy for DCIS. Further work is necessary to understand why young women have higher recurrence rates and to determine what the optimal treatment for younger women is.”
Although the overall recurrence rate for women with DCIS and treated with breast-conserving surgery and radiation is relatively low, estimated to be 9% to 12% at 10 years, some researchers have found evidence that women who are younger at the time of diagnosis are at higher risk of local recurrence.
With that concern in mind, Dr. Kong and her colleagues used administrative databases to assess local recurrence rates among younger women treated for DCIS between 1994 and 2003 in Ontario. They identified 5,744 women diagnosed with DCIS during the study period, 1,659 of whom were age 50 or younger at the time of diagnosis. Of those, 624 were treated with lumpectomy and radiation, and they were the women in the study cohort.
With a median follow-up of 7.8 years, 96 women (15%) had local recurrence of their disease. Breaking the recurrences down by age at diagnosis, the researchers found that 14 of the 70 women (20%) age 39 or younger had a local recurrence, as did 38 of the 198 (19%) age 40 to 44. By comparison, just 44 of the 356 (12%) 45 to 50 had a local recurrence.
Moreover, the women 45 and under had a 6% to 7% reduction in their estimated local recurrence-free survival at five and 10 years, compared with women 45 to 50 years at diagnosis. The hazard ratio for local recurrence-free survival was 1.7 for the women under 40 and 1.64 for women between 40 and 44. The difference remained statistically significant even after the investigators accounted for the use of boost radiotherapy, nuclear grade 3 pathology, and year of diagnosis. There was also a trend for a higher risk of invasive recurrence in the younger women, but the difference did not reach statistical significance.
To put the Dr. Kong's data into context, Lawrence J. Solin, MD, Chair of the Department of Radiation Oncology at Albert Einstein Medical Center in Philadelphia, the Discussant for the paper, presented summary data from the State of the Science meeting on DCIS, which was sponsored by the National Cancer Institute earlier this fall (OT, 10/25/09).
Four randomized controlled trials have compared breast-conserving therapy with and without radiation for women with DCIS. When the results of those trials are combined, the benefit of radiation appears to be a 15% reduction in risk of local recurrence at 10 years in all women, unselected for age.
Subset analysis showed that the benefit was somewhat less, however, in women under age 50. There was no apparent difference in disease-specific mortality between younger and older patients, although the trials were not powered to look at survival.
As for the data on younger women in particular, Dr. Solin noted that Aurelius Omlin, MD, and colleagues published a study in 2006 in which they examined local recurrence rates in nearly 400 women who were 45 or younger at the time of DCIS diagnosis. Age was found to be a significant risk factor for recurrence, with women under 40 having a significantly higher risk compared with women between 40 and 45.
One point Dr. Solin emphasized, and which was raised during the questions following Dr. Kong's presentation, is that age appears to be a continuous variable in terms of risk and that splitting a population at 40 or 45 is arbitrary. In fact, Dr. Solin said that when he looked at Dr. Kong's data, he thought the data supported that point. Dr. Kong concurred and said that her group was currently analyzing their data in that manner. She also noted, however, that from their current analysis, 45 was the proper cutoff for younger women.
Another question that arose during the audience discussion of Dr. Kong's study was the role of margin status in recurrence. The questioner hypothesized that perhaps surgeons were reluctant to take out a large volume of tissue from a younger woman for cosmetic reasons.
Dr. Kong said she and her colleagues had considered that possibility and that they were trying to obtain more complete pathological information than was available from the administrative databases to look at tissue volume and margin status.
Dr. Solin also raised the issue of margin status during his discussion. He pointed out that in Omlin's study, the investigators found a 3.5-fold increased risk of recurrence associated with positive margins relative to negative margins. In contrast, data from a non-age selected population in a European Organization for Research and Treatment of Cancer trial showed a 1.8-fold increase in risk of recurrence associated with positive margins.
“Particularly in younger patients, it may be even more important to get clear margins,” Dr. Solin said.
Not Screening Detected
Another factor that might influence the risk of recurrence in younger women is the fact that most of these are not screen-detected cancer, and that could be an adverse characteristic in itself because such cancers tend to be larger and may be later stage than those detected during routine screening, Dr. Solin said.
One bit of good news he shared from the summary of the four randomized trials is that the risk of cardiac problems did not appear to increase in women treated with radiation, even younger women.
“Especially in a younger patient cohort, where these patients are going to live for some time, it is important that we do no harm when we add radiation treatment,” he said. “I think the overview is comforting to those of us who add radiation treatment in that regard.”
© 2009 Lippincott Williams & Wilkins, Inc.