A new study finds that the use of whole breast irradiation (radiation therapy [RT]) after lumpectomy significantly reduced all and invasive ipsilateral breast recurrence (IBR) in women with good-risk ductal carcinoma in situ (DCIS). Conducted by NRG Oncology, the National Cancer Institute's National Clinical Trials Network group, NRG-RTOG 9804 was a randomized trial designed to assess the impact of whole breast RT versus observation (OBS) in women with "good-risk" DCIS, following lumpectomy, with long-term results focusing on IBR, the primary outcome (J Clin Oncol 2021; doi: 10.1200/JCO.21.01083).
As the researchers noted in the study, the widespread use of screening mammography identifies good-risk DCIS in thousands of women each year. The information gleaned from these scans supports the decision to treat patients with good-risk DCIS who want to minimize their in-breast recurrence, as well as particularly invasive risk, in the long-term. According to the study authors, the results of this trial provide "critical information that can inform shared patient-physician treatment decisions."
Study Details
For the trial, eligible patients underwent lumpectomy for DCIS that was mammogram detected, size <=2.5 cm, final margins >=3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional.
IBR was the primary endpoint in the study. The secondary endpoints were invasive IBR, contralateral breast events, overall and disease-free survival, distant metastasis, subsequent mastectomy, and toxicity. The researchers measured both primary and secondary endpoints from the date of randomization to date of recurrence or last follow-up for patients.
Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios. A total of 636 women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm, with 76 percent of patients being considered post-menopausal at study entry. All patients who participated on NRG-RTOG 9804 received annual mammography and specified clinical exam intervals. For this analysis, the median follow-up time was 13.9 years.
At median follow-up, the 15-year cumulative incidence of IBR was 7.1 percent with RT versus 15.1 percent with observation, and for invasive LR was 5.4 percent RT versus 9.5 percent with observation. On multivariable analysis, only RT and tamoxifen use were associated with reduced IBR.
The study found that RT greatly decreased all and invasive IBR with durable results at 15 years. While stating that the results are "not an absolute indication for RT," the authors noted that the findings "should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long-term following lumpectomy."
While DCIS is a non-invasive cancer, treatment is generally recommended to lower an individual's risk of developing invasive breast cancer recurrence, said Eileen Rakovitch, MD, FRCP(C), MSc, Vice Chair of Clinical Affairs, and a professor and scientist in the Department of Radiation Oncology at the University of Toronto, and one of the study's co-authors.
The development of invasive breast cancer requires additional treatment, "and can be very distressing," said Rakovitch, who is also the L.C. Campbell Chair in Breast Cancer Research at Sunnybrook Health Sciences Centre.
"The administration of breast radiation (RT) has been shown to reduce the risk of recurrence, but the benefit of RT in individuals with low-risk features of DCIS was unclear," she added, noting that this study demonstrates that breast RT can lower the 15-year risk of IBR (DCIS or invasive) by 8 percent and invasive breast recurrence by 4 percent for women with low-risk DCIS.
"This important finding will help future individuals diagnosed with low-risk DCIS," said Rakovitch, "by providing a better understanding of the risks of future recurrence and the potential benefit of breast RT."
Radiation after a lumpectomy for low-risk DCIS "isn't about survival," added study co-author Wendy Woodward, MD, PhD, Professor and Section Chief in the Department of Radiation Oncology and Deputy Department Chair, Faculty Support, at The University of Texas MD Anderson Cancer Center.
"These patients are unlikely to die of breast cancer, regardless of what they choose, and radiation isn't impacting that," said Woodward, who is also Deputy Director of the Morgan Welch IBC Clinic and Research Program at MD Anderson. "Instead, it's about reducing the chance of having to deal with it again, have more surgery, worry about it. It is a component of shared decision-making.
"For some patients, it's good news that risk of recurrence is low without radiation, and for some it's good news that they can make the risk as low as possible and add reassurance with radiation," Woodward stated. "The data that support short-course radiation, including 1 week of partial breast, mean the treatment is easy and brief for those interested in doing more. It's definitely not a one-size-fits-all study."
Mark McGraw is a contributing writer.