Radiation therapy after breast-conserving surgery reduced the already-low risk of recurrence by more than 70% in patients with defined “good-risk” breast cancer, according to a long-term clinical trial report presented at the 2018 Annual Meeting of the American Society for Radiation Oncology (ASTRO).¹ Data from the only prospective, randomized trial to compare recurrence outcomes after treatment for low-risk ductal carcinoma in situ showed that the 12-year cumulative incidence of local recurrence was 2.8% with whole-breast radiation vs 11.4% with observation alone (P = .0001). The cumulative incidence of invasive local recurrence (as opposed to ductal carcinoma in situ recurrence) also dropped to 1.5% with whole-breast radiation vs 5.8% with observation (P = .016).

We feel strongly that either the patient or doctor should use this information for a meaningful discussion about risks, benefits, and the patient’s own degree of comfort.

— Beryl McCormick, MD, FACR

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“This larger-than-expected reduction has yielded meaningful results despite not meeting some of the original targeted accruals,” said Beryl McCormick, MD, FACR, a radiation oncologist and Chief of External Beam Radiotherapy Service at Memorial Sloan Kettering Cancer Center, New York. “Because this is not a life-threatening disease, we feel strongly that either the patient or doctor should use this information for a meaningful discussion about risks, benefits, and the patient’s own degree of comfort, which varies greatly in terms of local tumor control with or without radiation.”

“For many patients, a recurrence risk of 1% per year without radiation is not very worrisome,” Dr. McCormick added. “But other patients will prefer to do everything they can not to have this disease comeback, and that would certainly mean adding radiation.”

Study Details

As Dr. McCormick explained, unlike previous prospective studies comparing whole-breast radiation therapy with no radiotherapy for ductal carcinoma in situ, Radiation Therapy Oncology Group (RTOG) 9804 included “good-risk” patients alone. Investigators defined “good risk” as ductal carcinoma in situ detected by mammogram with a size less than or equal to 2.5 cm, final margins of at least 3 mm, and low or intermediate nuclear grade determined by a pathologist.

Following surgical excision, the investigators randomly assigned patients to receive either whole-breast radiation with standard doses or observation. Boosts were not allowed, but the use of tamoxifen for 5 years was optional. Study endpoints included local failure, contralateral breast failure, and the need for salvage mastectomy.

As Dr. McCormick reported, although intended accrual was 1,790 patients, just 636 women were randomly assigned to the study between 1999 and 2006, with initial results reported in 2013. For this long-term update, in addition to the analyses for the 585 eligible patients with follow-up, sensitivity analyses were performed including all patients with follow-up (n = 629). The median age for patients was 58 years, including 76% of the study patients were postmenopausal.

The mean pathologic tumor size was 0.60 cm (61% were 0.5 cm or smaller, 65% had a margin width of 1.0 cm or larger or a completely negative re-excision specimen). The highest nuclear tumor grade was 1, found in 44% of patients, and grade 2 tumors were diagnosed in the remaining 56%. Although the intention to use tamoxifen was indicated equally between treatment arms, 58% of patients randomly assigned to whole-breast radiation received tamoxifen vs 65% of patients in the observation arm.

Key Findings

Despite not meeting original targeted accrual, the authors noted that the larger-than-expected reduction in local recurrence yielded meaningful results. With a median follow-up of 12.4 years, the cumulative incidence of local recurrence was 2.8% with whole-breast radiation vs 11.4% with observation alone (P = .0001, hazard ratio [HR] = 0.26). The 12-year cumulative incidence of invasive local recurrence was 1.5% with whole-breast radiation and 5.8% with observation (P = .016, HR = 0.34).

Following multivariate analysis, whole-breast radiation (HR = 0.25, P = .0003) and tamoxifen (HR = 0.50, P = .024) were associated with a reduced rate of local failure. As expected, said Dr. McCormick, no significant differences were observed in survival, disease-free survival, or use of mastectomy. Although the rates of adverse events were higher in patients receiving radiation, acute toxicities were still “very, very low,” according to Dr. McCormick, with just 3.5% of patients experiencing grade 3 or higher toxicities in the experimental arm.

Dr. McCormick and colleagues are planning to combine these results with a single-arm study from the Eastern Cooperative Oncology Group that looked at the same low-risk patients but did not offer radiation. Although some of these patients received tamoxifen, Dr. McCormick noted, others did not. “We’d like to see how much impact tamoxifen alone has in this ‘good-risk’ group of patients,” she concluded. ■

DISCLOSURE: Dr. McCormick reported no conflicts of interest.

REFERENCE

1. McCormick B: Randomized trial evaluating radiation following surgical excision for “good risk” DCIS: 12-Year report from NRG/RTOG 9804. 2018 ASTRO Annual Meeting. Abstract LBA1. Presented October 21, 2018.