Lumpectomy Plus RT Tied to Lower Mortality in DCIS

But Routine Radiation Not Advised

Nick Mulcahy

August 10, 2018

Lumpectomy plus radiotherapy is associated with a statistically significant reduced risk for breast cancer–related death compared with either lumpectomy or mastectomy alone in women with ductal carcinoma in situ (DCIS), new research indicates.

But the clinical benefit is small, say senior author Steven Narod, MD, of the University of Toronto in Canada, and colleagues.

For their study, the team reviewed records from the Surveillance, Epidemiology, and End Results (SEER) database on women who received an initial diagnosis of primary DCIS between 1998 and 2014.

They identified 140,366 patients, nearly half (46.5%) of whom were treated with lumpectomy and radiotherapy; 28.5% were treated with mastectomy, and 25% with lumpectomy alone.

The investigators found that the actuarial 15-year breast cancer mortality rate was 1.74% for patients treated with lumpectomy and radiotherapy, 2.33% for patients treated with lumpectomy alone, and 2.26% for patients treated with mastectomy alone.

This translated into a 23% reduction in the relative risk for breast cancer mortality with the breast-conserving combination therapy (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67 - 0.88; P < .001).

The new results do not necessarily imply that radiotherapy should be used in conjunction with lumpectomy, however, the team indicates.

"The absolute risk reduction was only 0.27%, and it is doubtful whether a benefit of this size is large enough to warrant [routine] radiotherapy. It would be necessary to treat 370 women to save 1 life," they point out.

The authors believe that the impact of radiotherapy on survival in this setting is "likely not due to local control but rather systemic effects," but the exact mechanism of action in uncertain.

The study, which used a matched-pair design that included a wide variety of matches, such as age at diagnosis, tumor grade, and estrogen-receptor status, was published online August 10 in JAMA Network Open.

However, in accompanying editorial, a pair of experts say that the study, which they call "rigorous," may suffer from confounding, a bugaboo of observational research.

Most notably, use of endocrine therapy was not controlled for and therefore may be a factor for which the treatment groups were not well matched, write Mira Goldberg, MD, a medical oncologist, and Timothy Whelan, BM, BCh, a radiation oncologist, who are both from the Juravinski Cancer Center of McMaster University, Hamilton, Ontario, Canada.

Additionally, at baseline, estrogen receptor–positive disease was more common in patients treated by lumpectomy with radiotherapy than in the other two groups, which could potentially have led to a higher use of endocrine therapy in that group, they note.

Such a discrepancy "could potentially influence the observed treatment effects," the editorialist comment.

Highly unlikely, suggested Narod in response.

"There are no papers to my knowledge which show that tamoxifen reduces mortality in DCIS," he told Medscape Medical News in an email.

"It is disingenuous to assume that the measured effect of radiotherapy could be accounted for as an unmeasured effect of tamoxifen (with an unproven benefit) in a matched analysis," Narod argued.

Narod and his coauthors anticipated this issue in their article, saying: "We believe that the mortality benefit is attributable to radiotherapy and not to a baseline imbalance in pathologic features or treatments."

These authors previously employed this same DCIS SEER data set, but in a study involving 108,000 cases from 1988 to 2011 ( JAMA Oncol . 2015;1:888-896).

In that study, the investigators observed a nonsignificant decrease in breast cancer mortality associated with radiotherapy after lumpectomy, as reported by Medscape Medical News. The results from that study led to a call to rethink aggressive and immediate treatment of DCIS.

The Upshot of the Data

In their editorial, Goldberg and Whelan point out that other research indicates that DCIS patients who have good prognostic factors and≤10% risk for local recurrence at 10 years are unlikely to benefit from radiotherapy ( J Clin Oncol . 2015;33:709-715).

Furthermore, "there is increasing interest in using molecular markers to better identify patients at lower risk for whom radiotherapy may be omitted," they say.

In this context, the results of the new study by Narod and colleagues are "reassuring," the editorialists say.

"The risk of breast cancer mortality in patients with DCIS was very low, and the potential absolute benefit of radiotherapy was quite small," they write.

Omit radiotherapy after lumpectomy in low-risk DCIS patients — that's the message of the new study, say the editorialists.

They say that is an especially good idea because of the negative effects of radiation treatment — "the cost and inconvenience of 5 to 6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers."

Dr Whelan has received research support from Genomic Health. Lead study author Vasily Giannakeas, MPH, was supported by the Canadian Institutes of Health Research Frederick Banting and a Charles Best Doctoral Research Award.

JAMA Network Open. Published online August 10, 2018. Full text, Editorial

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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