JNCI: Radiotherapy + tamoxifen cuts invasive breast cancer recurrence in half

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Across a 15-year study of more than 2,600 women who underwent lumpectomies for breast cancer, radiation therapy cut the likelihood of invasive ipsilateral breast tumor recurrence (I-IBTR) in half, while taking tamoxifen reduced I-IBTR by an additional 32 percent, according to a study published March 16 in the Journal of the National Cancer Institute.

Clinically occult ductal carcinoma in situ (DCIS) accounts for approximately 25 percent of new breast cancer cases, and although breast-conserving surgery to treat DCIS is common and yields a strong prognosis, I-IBTR is likewise frequent in survivors. The authors provided an update to two previous studies, commencing in 1985 and 1991, which were part of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the NSABP B-17 and B-24 studies.

With a median follow-up of 15 years, the researchers assessed rates of I-IBTR and prognosis in patients who were treated with lumpectomy only; lumpectomy plus radiotherapy; and lumpectomy, radiotherapy and tamoxifen. A total of 2,612 women in both trials were included in the present study.

IBTR constituted the most common first failure in both treatment groups, with a combined total of 490 cases during follow-up, the majority of which (263) were invasive. Thirty-four other local, regional or distant recurrences occurred in patients without I-IBTR.

Patients treated after their first breast cancers with lumpectomy plus radiotherapy showed a 52 percent reduction in the risk of I-IBTR compared with the lumpectomy-only group. Moreover, patients who were treated with radiotherapy and tamoxifen were 32 percent less likely to experience I-IBTR than the lumpectomy plus radiotherapy group.

Comparing across groups, patients who were treated with both radiotherapy and tamoxifen faced a 70 percent reduction in risk of I-IBTR compared with lumpectomy-only patients. Cumulative I-IBTR rates after 15 years were 19.4 percent among lumpectomy-only patients, 8.9 percent in lumpectomy plus radiotherapy patients and 8.5 percent in the radiotherapy plus tamoxifen group.

A total of 385 participants died within the 15-year follow-up period, though only 72 of these deaths were attributed to breast cancer, 22 to I-IBTR. Between groups, patients who received radiotherapy and tamoxifen had a nonsignificant 32 percent reduction in mortality compared with all patients not treated with tamoxifen. Despite the varying recurrence rates, no statistically significant differences in mortality were observed between treatment groups.

Patients with I-IBTR experienced a significantly higher likelihood of death (hazard ratio 7.06), while recurrent DCIS presented no significant mortality risk.

“The NSABP B-17 and B-24 trials represent the largest prospective evaluation of breast-conserving therapies for DCIS to date,” said Irene L. Wapnir, MD, from the department of surgery at Stanford University School of Medicine in Stanford, Calif, and colleagues. “Long-term findings in these studies demonstrate the effectiveness of this approach in the management of DCIS.”

The authors argued that their findings agreed with those of similar trials, including the European Organization for Research and Treatment of Cancer Trial 10853 and the Swedish Trial.

Wapnir and co-researchers considered the 20-year old study design a potential limitation, given the improvements accomplished in diagnostic imaging over the time period. However, the authors did note that no correlation between first tumor size and risk of I-IBTR was discovered and that most tumors were, in fact, small. Additionally, the researchers acknowledged that the inclusion of some cases with uncertain surgical margins introduced heterogeneity that might have obscured treatment effects, while tumor hormone receptor and HER2 receptor assessment, both of which are now known to be important in DCIS, were not assessed.

“In this update of the trials, we showed that 19.4 percent of patients who received LO [lumpectomy only] for treatment of DCIS had developed an I-IBTR after 15 years compared with 8.5 percent of patients who received LRT + TAM [lumpectomy, radiotherapy and tamoxifen]. I-IBTR was associated with increased mortality risk, whereas there was no association with recurrence of DCIS, and neither overall nor breast cancer-specific survival differed between the LO, LRT [lumpectomy and radiotherapy], and LRT + TAM treatment groups,” the authors summed.

“In conclusion, we believe that these long-term findings