Adjuvant tamoxifen was associated with a reduced risk of 15-year ipsilateral breast cancer recurrence as well as invasive ipsilateral breast cancer recurrence in patients with “good-risk” ductal carcinoma in situ (DCIS) who omitted radiation therapy after breast-conserving surgery, according to a combined analysis of the phase III NRG Oncology/RTOG 9804 and the phase II ECOG-ACRIN E5194 trials. However, the analysis also found that adjuvant tamoxifen did not reduce the risk of ipsilateral DCIS or contralateral breast cancer. The results were presented at the 2024 San Antonio Breast Cancer Symposium.1
At 15 years, patients who received tamoxifen had a statistically significant reduction in ipsilateral breast recurrence compared with patients who did not receive tamoxifen (11.4% vs 19.0%), representing a 48% risk reduction in ipsilateral breast cancer recurrence (P = .001). Tamoxifen did significantly impact invasive ipsilateral breast cancer; the 15-year rate was 6.0% vs 11.5% in those who did not receive it (P = .005). However, adjuvant tamoxifen did not significantly reduce the 15-year risk of DCIS ipsilateral breast cancer recurrence compared with nonreceipt of tamoxifen (5.5% vs 8.1%, respectively). Nor did tamoxifen reduce the incidence of contralateral breast cancer. These findings suggest that for this select group of patients (ie, good risk as defined in the trial), it may be acceptable to forgo radiation after surgery, assuming they adhere to a full course of endocrine therapy.
Jean L. Wright, MD, FASTRO
“In the absence of a survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared-decision process, and I think these data help us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk DCIS,” said lead author Jean L. Wright, MD, FASTRO, Chair and Professor, Department of Radiation Oncology at the University of North Carolina School of Medicine at Chapel Hill.
“We now have more thorough data to present to patients who are considering omitting radiation therapy with respect to their endocrine therapy decision. The data suggest it is reasonable for good-risk DCIS patients to forgo radiation. The role of endocrine therapy is less well established. Most modern studies have left the use of endocrine therapy to physicians, and the practice is highly variable. Our data show that it is important to evaluate the impact of endocrine therapy [for patients] who do not receive radiation therapy,” Dr. Wright explained.
Study Details
Patients were included in the ancillary analysis of the NRG Oncology/RTOG 9804 and ECOG-ACRIN E5194 trials if they were considered to have “good-risk” DCIS after breast-conserving surgery. For purposes of the study, “good risk” was defined as low or intermediate-grade DCIS with a tumor size up to 2.5 cm, grade 1 or 2, and a surgical margin of at least 3 mm. In the NRG Oncology/RTOG 9804 trial, 317 patients fulfilled the definition of good risk and did not have radiation therapy; in the ECOG-ACRIN E5194 trial, in which no patients received radiation therapy, 561 patients met the definition, for a total of 878 patients included in the analysis.
The use of tamoxifen was optional but tracked in both trials. In the NRG Oncology/RTOG 9804 trial, 66% of patients used tamoxifen, and 34% did not. The respective percentages in the ECOG/ACRIN E5194 trial were 30% and 70%. This variation in tamoxifen use between the two studies reflects the lack of standardization in tamoxifen use for DCIS.
The majority of patients adhered to the 5-year prescribed course of tamoxifen. Across both trials, the median patient age was 59 years, and 80% of patients were aged 50 or older. Additionally, 89% of patients were White.
Almost two-thirds of patients with DCIS (61%) had a surgical margin width between 3 and 9 mm, and 19% had a margin width of 10 mm or greater. Additionally, 48% of patients had a DCIS size of 5 mm or smaller, 35% had a DCIS size between 6 and 10 mm, and 17% had a DCIS size greater than 10 mm.
Most patients had grade 2 DCIS (56%). A subset of patients initially classified as low or intermediate grade were upgraded to grade 3 (13%) after pathology review was conducted in the ECOG-ACRIN E5194 study.
Key Results
Subgroup analysis showed that the benefit of tamoxifen was greater in patients with a surgical margin width of 10 mm or greater and DCIS size of 10 mm or greater.
Dr. Wright and coauthors were surprised that no reduction in contralateral breast events was observed with tamoxifen in this analysis. The 15-year rate of contralateral breast events was 5.6% in the tamoxifen group and 8.8% in the no-tamoxifen group, a difference that was not statically significant.
Virginia Kaklamani, MD
Additional Commentary
At a press conference where these data were discussed, moderator Virginia Kaklamani, MD, also found the lack of impact of tamoxifen on contralateral breast cancer “surprising.” She added: “I always struggle about how to talk to patients regarding 5 years of tamoxifen vs 5 weeks of radiation,” she said. Dr. Kaklamani is Co-Director of SABCS and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center.
EXPERT POINT OF VIEW
“It was surprising that there was so little effect on contralateral disease,” agreed formal discussant of the NRG Oncology/RTOG 9804 and ECOG-ACRIN E5194 trials, Elinor Sawyer, MBBS, PhD, a consultant clinical oncologist at King’s College London, United Kingdom.
Elinor Sawyer, MBBS, PhD
“This decrease in ipsilateral invasive recurrence [with tamoxifen] is really important, because there are studies showing that the development of an invasive recurrence after DCIS [ductal carcinoma in situ] is associated with a worse prognosis than a pure DCIS recurrence,” she noted.
Dr. Sawyer continued: “The main feature we want to focus on is this was a group of patients with very clear inclusion criteria of this good-risk DCIS. Even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So, I’m wondering if perhaps it’s related to the fact that patients who were enrolled in these studies had low-risk features and a lower risk of contralateral breast events as compared with a broader population of patients with DCIS,” she suggested. ■
DISCLOSURE: The combined analysis was supported by grants from the National Cancer Institute. Dr. Wright has received honoraria from the American Society for Radiation Oncology. Dr. Kaklamani has served as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead Scienes, Lilly, Menarini, and Novartis; and has received research support from Eisai. Dr. Sawyer has received research support from Pfizer, Seagen, and IQVIA.
REFERENCE
- Wright JL: Impact of tamoxifen only after breast conservation surgery for “good risk” duct carcinoma in situ: Results from the NRG Oncology/RTOG 9804 and ECOG-ACRIN E5194 trials. 2024 San Antonio Breast Cancer Symposium. Abstract GS2-02. Presented December 12, 2024.
