Reframing hormone-positive DCIS management: Effects of adjuvant therapies and surgical extent on any invasive recurrence.

572 Background: The treatment of DCIS is still primarily informed by trials that are now decades old. We have learned since then that only invasive subsequent events, not in situ ones, increase a woman’s risk of eventual metastasis and breast cancer mortality, and may necessitate more aggressive systemic treatment. This suggests a need for the reassessment of the impact of adjuvant therapies. Methods: Women diagnosed with a first breast cancer of unilateral hormone positive DCIS undergoing breast conserving surgery were identified in the Surveillance, Epidemiology and End Results Program registry. Propensity-matching was performed between treatment groups using age, race, lesion size and grade. Competing risks methods were used to estimate the cumulative incidence of any invasive event at 10 years and subdistribution hazard ratios (sHRs) were calculated from multivariate models adjusting for the same covariates used for matching. Results: A total of 14,189 patients diagnosed from 2007 to 2011 were eligible for matching, among whom 900 (6.3%) suffered a subsequent invasive event.A cohort was developed by matching from the smallest treatment group, lumpectomy with endocrine therapy. There were 2,996 matched patients, among whom 511 (17.1%) had an invasive subsequent event. Adjuvant endocrine therapy was associated with reduced risk of any invasive event (sHR=0.38, p<0.001) compared to patients undergoing lumpectomy without adjuvant therapy. Radiotherapy alone was not associated with reduced risk (sHR=1.03, p=0.81): it was associated with reduced risk of an ipsilateral invasive event (sHR=0.65, p=0.006) but an increased risk of a contralateral invasive event (sHR=1.50, p=0.01). In subgroup analyses, lumpectomy with radiation therapy was noted to be non-significantly associated with increased risk of any invasive disease in patients younger than 60 years (sHR=1.38, p=0.053) and with decreased risk in patients 60 years or older (sHR=0.79, p=0.12). Conclusions: Our results suggest that endocrine therapy may confer the greatest risk reduction to the development of any subsequent invasive recurrences, and whole-breast radiotherapy may be associated with increased risk for younger women. The risk posed by DCIS as a high-risk marker may outweigh its risk as a premalignant lesion. Any invasive subsequent breast cancer, and subgroup analyses by age. Only treatment effect shown, but results are adjusted for race, grade, age, and lesion size. Any Invasive, Any Age Any Invasive, < 60 years old Any Invasive, ≥ 60 years old sHR (95% CI) p sHR (95% CI) p sHR (95% CI) p Treatment BCS Ref - Ref - Ref - BCS + ET 0.38 (0.29-0.51) <0.001 0.34 (0.21-0.54) <0.001 0.40 (0.28-0.58) <0.001 BCS + RT 1.03 (0.82-1.28) 0.81 1.38 (1.00-1.91) 0.053 0.79 (0.59-1.07) 0.12 sHR = Subdistribution hazard ratio. BCS=Breast conservation surgery. ET=Endocrine therapy. RT=Radiation therapy.