A new analysis presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) reveals that adjuvant tamoxifen significantly reduces the 15-year risk of ipsilateral breast cancer recurrence in patients with good-risk ductal carcinoma in situ (DCIS) who did not receive radiation therapy after breast-conserving surgery. The combined analysis of the phase III NRG Oncology/RTOG 9804 and the phase II ECOG-ACRIN E5194 trials offers crucial insights for treatment decisions in this patient population.
Impact of Tamoxifen on Recurrence Rates
The study, led by Jean L. Wright, MD, FASTRO, Chair and Professor of Radiation Oncology at the University of North Carolina School of Medicine at Chapel Hill, included 878 patients with good-risk DCIS. 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. The analysis showed that patients who received tamoxifen had a statistically significant reduction in ipsilateral breast recurrence compared to those who did not (11.4% vs 19.0%, P = .001), representing a 48% risk reduction.
Specifically, tamoxifen significantly impacted invasive ipsilateral breast cancer, with a 15-year rate of 6.0% in the tamoxifen group compared to 11.5% in the non-tamoxifen group (P = .005). However, the study found that adjuvant tamoxifen did not significantly reduce the 15-year risk of DCIS ipsilateral breast cancer recurrence (5.5% vs 8.1%) or the incidence of contralateral breast cancer.
Clinical Implications and Shared Decision-Making
Dr. Wright emphasized the importance of these findings for clinical practice, stating, "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."
The study's results suggest that for carefully selected patients with good-risk DCIS, it may be acceptable to forgo radiation after surgery, provided they adhere to a full course of endocrine therapy. This is particularly relevant given the variability in endocrine therapy use for DCIS, as highlighted by the differing rates of tamoxifen use in the two trials (66% in NRG Oncology/RTOG 9804 vs 30% in ECOG/ACRIN E5194).
Study Details and Patient Characteristics
The median patient age across both trials was 59 years, with 80% of patients aged 50 or older, and 89% were White. Most patients (61%) had a surgical margin width between 3 and 9 mm, and nearly half (48%) had a DCIS size of 5 mm or smaller. The majority (56%) had grade 2 DCIS.
Subgroup analysis indicated that the benefit of tamoxifen was more pronounced in patients with a surgical margin width of 10 mm or greater and a DCIS size of 10 mm or greater.
Expert Commentary
Virginia Kaklamani, MD, Co-Director of SABCS and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, noted the surprising lack of impact of tamoxifen on contralateral breast cancer. Elinor Sawyer, MBBS, PhD, a consultant clinical oncologist at King’s College London, UK, highlighted the importance of the decrease in ipsilateral invasive recurrence with tamoxifen, as invasive recurrence after DCIS is associated with a worse prognosis than pure DCIS recurrence.
Dr. Sawyer also cautioned that the study population had very specific inclusion criteria for good-risk DCIS, with smaller DCIS sizes than the upper limit allowed by the criteria. This may limit the generalizability of the findings to a broader population of DCIS patients.
Conclusion
This analysis provides valuable data for clinicians and patients making treatment decisions for good-risk DCIS. The findings support the consideration of tamoxifen as a viable option to reduce the risk of recurrence, particularly invasive recurrence, in patients who forgo radiation therapy after breast-conserving surgery.
