Re: Li PC, Zhang Z, Cronin AM, Punglia RS. Mortality After Invasive Second Breast Cancers Following Prior Radiotherapy for DCIS. J Natl Compr Canc Netw 2019;17(11):1367–1371.
We read with interest the article by Li et al1 regarding the impact of prior radiotherapy (RT) for ductal carcinoma in situ (DCIS) on the prognosis of women with invasive breast cancer. The authors report that the risk of breast cancer mortality following invasive breast cancer among women with a prior diagnosis of DCIS is 1.7 times higher if the DCIS was treated with lumpectomy + RT versus lumpectomy alone (adjusted hazard ratio [HR], 1.70; 95% CI, 1.18–2.45; P=.005). The authors suggest that this finding may have implications for the use of RT in the initial treatment of DCIS. However, we propose another interpretation.
Treatment of DCIS with lumpectomy + RT, compared with lumpectomy alone, is associated with a large reduction in the risk of subsequent ipsilateral invasive breast cancer but little or no reduction in the risk of breast cancer mortality.2,3 In SEER, we compared the risks of ipsilateral invasive recurrence and of breast cancer–specific mortality among patients with DCIS treated with lumpectomy ± RT using one-to-one matching.2 In this analysis (including 29,465 propensity-matched pairs of patients), the use of RT after lumpectomy was associated with a 36% reduction in the 15-year risk of ipsilateral invasive breast cancer (8.1% vs 5.2%; absolute reduction of 2.9%) and a small reduction in the risk of breast cancer mortality (2.0% vs. 1.8%; absolute reduction of 0.2%). The ratio of deaths to recurrences increased from 0.25 in patients treated with lumpectomy alone to 0.35 in patients treated with lumpectomy + RT; therefore, for every 10,000 patients treated with lumpectomy alone, we would expect approximately 810 ipsilateral invasive recurrences and 200 breast cancer deaths, whereas for every 10,000 patients treated with lumpectomy + RT, we would expect 520 ipsilateral invasive recurrences and 180 breast cancer deaths. These numbers correspond to a HR for death associated with RT of approximately 1.40, suggesting that the HR of 1.70 generated by Li et al1 may in part be explained by a reduction in the number of cases (ie, patients with recurrence after DCIS) but no reduction in the number of deaths.
Li PC, Zhang Z, Cronin AM, Punglia RS. Mortality after invasive second breast cancers following prior radiotherapy for DCIS. J Natl Compr Canc Netw 2019;17:1367–1371.
Giannakeas V, Sopik V, Narod SA. Association of radiotherapy with survival in women treated for ductal carcinoma in situ with lumpectomy or mastectomy. JAMA Netw Open 2018;1:e181100.
Garg PK, Jakhetiya A, Pandey R, et al. Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in-situ: a meta-analysis of randomized controlled trials. Breast J 2018;24:233–239.