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1 Supplementary Online Content 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(4):e doi: /jamanetworkopen etable 1. Excluded Cases of Stage 0 Breast Cancer Identified in SEER From 1998 to 2014 etable 2. Matched DCIS Patients Treated With Lumpectomy Alone Versus Lumpectomy and Radiation etable 3. Matched DCIS Patients Treated With Lumpectomy Alone Versus Mastectomy etable 4. Matched DCIS Patients Treated With Lumpectomy and Radiation Versus Mastectomy etable 5. Breast Cancer-Specific Mortality Rates From DCIS Diagnosis for the Entire Cohort and According to Treatment Group (Mastectomy, Lumpectomy Alone, Lumpectomy and Radiotherapy) etable 6. Hazard Ratios Associated With Radiation/Extent of Surgery Using Multivariate Cox Regression, Inverse Probability Treatment Weighting and 1:1 Propensity Score-Based Matching, With and Without Accounting for Competing Risks of Death Among Matched Subgroups etable 7. Breast Cancer-Specific Mortality And Ipsilateral Invasive Recurrence Rates From DCIS Diagnosis Among Matched DCIS Patients Treated With Lumpectomy Alone Versus Lumpectomy and Radiation etable 8. Breast Cancer-Specific Mortality and Ipsilateral Invasive Recurrence Rates From DCIS Diagnosis Among Matched DCIS Patients Treated With Mastectomy Versus Lumpectomy and Radiation efigure 1. Breast Cancer-Specific Survival Post-DCIS in Propensity-Matched Patients Treated With Lumpectomy Alone vs. With Mastectomy efigure 2. Ipsilateral Invasive Recurrence-Free Survival Post-DCIS in Propensity-Matched Patients Treated With Lumpectomy and Radiation vs. With Lumpectomy Alone efigure 3. Breast Cancer-Specific Survival Post-DCIS in Propensity-Matched Patients Treated With Lumpectomy and Radiation vs. With Mastectomy efigure 4. Ipsilateral Invasive Recurrence-Free Survival Post-DCIS in Propensity-Matched Patients Treated With Lumpectomy and Radiation vs. With Mastectomy
2 efigure 5. Contralateral Invasive Breast Cancer-Free Survival Post-DCIS in PropensityMatched Patients Treated With Lumpectomy and Radiation vs. With Lumpectomy Alone This supplementary material has been provided by the authors to give readers additional information about their work.
3 etable 1. Excluded cases of stage 0 breast cancer identified in SEER from 1998 to 2014 Exclusion criteria Frequency Percent Cumulative Cumulative frequency percent 1. Prior cancers not in SEER 12, , First primary is not Stage 0 breast cancer 25, , Missing or no follow-up months 1, , LCIS 23, , Paget's disease 1, , Unknown/invasive histology type , Unknown laterality , Did not undergo surgery 3, , Unknown surgery 1, , Unknown radiation treatment 2, , Eligible for study 140, ,
4 etable 2. Matched DCIS patients treated with lumpectomy alone versus lumpectomy and radiation Value Lumpectomy alone Lumpectomy and radiation Standardized difference Number of patients 29,465 (50.0%) 29,465 (50.0%) Year of diagnosis ,446 (38.8%) 11,446 (38.8%) ,128 (31.0%) 9,128 (31.0%) ,891 (30.2%) 8,891 (30.2%) 0 Age at diagnosis Mean (SD) 60.4 (11.8) 60.4 (11.8) 0 Median (IQR) 60.0 ( ) 60.0 ( ) Ethnicity White 23,473 (79.7%) 23,440 (79.6%) 0 Black 3,041 (10.3%) 3,043 (10.3%) 0 East Asian 1,155 (3.9%) 1,212 (4.1%) 0.01 Southeast Asian 1,057 (3.6%) 1,024 (3.5%) 0.01 Other/Unknown 739 (2.5%) 746 (2.5%) 0 Annual household income, $ Mean (SD) 35,522.1 (8,103.4) 35,425.7 (8,092.8) 0.01 Median (IQR) 34,970.0 (30, ,610.0) 35,020.0 (29, ,610.0) Tumour grade I 4,639 (15.7%) 4,639 (15.7%) 0 II 11,569 (39.3%) 11,569 (39.3%) 0 III/IV 7,807 (26.5%) 7,807 (26.5%) 0 Unknown 5,450 (18.5%) 5,450 (18.5%) 0 Tumour size Mean (SD) 1.2 (1.6) 1.3 (1.3) 0.01 Median (IQR) 0.8 ( ) 0.9 ( ) ER status Negative 1,538 (5.2%) 1,538 (5.2%) 0 Positive 15,368 (52.2%) 15,368 (52.2%) 0 Unknown 12,559 (42.6%) 12,559 (42.6%) 0 PR status Negative 2,854 (9.7%) 2,934 (10.0%) 0.01 Positive 12,966 (44.0%) 12,983 (44.1%) 0 Unknown 13,645 (46.3%) 13,548 (46.0%) 0.01
5 etable 3. Matched DCIS patients treated with lumpectomy alone versus mastectomy Value Lumpectomy alone Mastectomy Standardized difference Number of patients 20,832 (50.0%) 20,832 (50.0%) Year of diagnosis ,115 (39.0%) 8,115 (39.0%) ,531 (31.4%) 6,531 (31.4%) ,186 (29.7%) 6,186 (29.7%) 0 Age at diagnosis Mean (SD) 59.1 (12.0) 59.0 (12.1) 0 Median (IQR) 58.0 ( ) 58.0 ( ) Ethnicity White 16,299 (78.2%) 16,262 (78.1%) 0 Black 2,211 (10.6%) 2,248 (10.8%) 0.01 East Asian 866 (4.2%) 843 (4.0%) 0.01 Southeast Asian 747 (3.6%) 798 (3.8%) 0.01 Other/Unknown 709 (3.4%) 681 (3.3%) 0.01 Annual household income, $ Mean (SD) 35,211.0 (8,236.8) 35,075.1 (8,228.1) 0.02 Median (IQR) 34,970.0 (30, ,610.0) 34,970.0 (29, ,610.0) Tumour grade I 2,312 (11.1%) 2,312 (11.1%) 0 II 7,918 (38.0%) 7,918 (38.0%) 0 III/IV 6,761 (32.5%) 6,761 (32.5%) 0 Unknown 3,841 (18.4%) 3,841 (18.4%) 0 Tumour size Mean (SD) 1.5 (2.1) 1.6 (1.8) 0.04 Median (IQR) 1.1 ( ) 1.2 ( ) ER status Negative 1,242 (6.0%) 1,242 (6.0%) 0 Positive 10,672 (51.2%) 10,672 (51.2%) 0 Unknown 8,918 (42.8%) 8,918 (42.8%) 0 PR status Negative 2,248 (10.8%) 2,361 (11.3%) 0.02 Positive 8,911 (42.8%) 8,818 (42.3%) 0.01 Unknown 9,673 (46.4%) 9,653 (46.3%) 0
6 etable 4. Matched DCIS patients treated with lumpectomy and radiation versus mastectomy Value Lumpectomy and radiation Mastectomy Standardized difference Number of patients 29,865 (50.0%) 29,865 (50.0%) Year of diagnosis ,217 (34.2%) 10,217 (34.2%) ,460 (31.7%) 9,460 (31.7%) ,188 (34.1%) 10,188 (34.1%) 0 Age at diagnosis Mean (SD) 57.1 (11.3) 57.0 (11.3) 0 Median (IQR) 56.0 ( ) 56.0 ( ) Ethnicity White 23,238 (77.8%) 23,152 (77.5%) 0.01 Black 3,214 (10.8%) 3,227 (10.8%) 0 East Asian 1,277 (4.3%) 1,317 (4.4%) 0.01 Southeast Asian 1,216 (4.1%) 1,227 (4.1%) 0 Other/Unknown 920 (3.1%) 942 (3.2%) 0 Annual household income, $ Mean (SD) 34,909.9 (8,346.4) 34,850.1 (8,368.5) 0.01 Median (IQR) 34,970.0 (28, ,610.0) 34,970.0 (28, ,610.0) Tumour grade I 2,441 (8.2%) 2,441 (8.2%) 0 II 9,957 (33.3%) 9,957 (33.3%) 0 III/IV 13,167 (44.1%) 13,167 (44.1%) 0 Unknown 4,300 (14.4%) 4,300 (14.4%) 0 Tumour size Mean (SD) 1.7 (1.6) 1.7 (1.6) 0.04 Median (IQR) 1.3 ( ) 1.5 ( ) ER status Negative 2,970 (9.9%) 2,970 (9.9%) 0 Positive 16,521 (55.3%) 16,521 (55.3%) 0 Unknown 10,374 (34.7%) 10,374 (34.7%) 0 PR status Negative 4,782 (16.0%) 4,846 (16.2%) 0.01 Positive 13,554 (45.4%) 13,480 (45.1%) 0 Unknown 11,529 (38.6%) 11,539 (38.6%) 0
7 etable 5. Breast cancer-specific mortality rates from DCIS diagnosis for the entire cohort and according to treatment group (mastectomy, lumpectomy alone, lumpectomy and radiotherapy) Year Complete DCIS Cohort Mastectomy Lumpectomy and radiation Lumpectomy alone FU time (years) Events Ann. Rate (%) Cum. Rate (%) FU time (years) Events Rate (%) Cum. Rate (%) FU time (years) Events Rate (%) Cum. Rate (%) FU time (years) Overall 986,201 1, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Events Rate (%) Cum. Rate (%) Abbreviations: Ann., annual; Cum., cumulative
8 etable 6. Hazard ratios associated with radiation/extent of surgery using multivariate cox regression, inverse probability treatment weighting and 1:1 propensity score-based matching, with and without accounting for competing risks of death among matched subgroups Comparison Model 1: matched subgroups (noncompeting risks model) Hazard Ratio P-value (95% CI) Model 2: matched subgroups (competing risks model)* Hazard Ratio P-value (95% CI) Model 3: inverse probability treatment weighting Hazard Ratio P-value (95% CI) Model 4: multivariate Cox regression** Hazard Ratio (95% CI) Lumpectomy alone Lumpectomy + radiation 0.77 ( < ( ( ( ) 0.96) 0.91) 0.92) Lumpectomy alone Mastectomy 0.91 ( ( ( ( ) 1.10) 1.04) 1.04) Mastectomy Lumpectomy + radiation 0.75 ( < (0.69 < (0.67 < ( ) 0.91) 0.90) 0.94) P-value *Model considers other non-breast cancer-specific deaths as competing risks **Adjusted for year of diagnosis (categorical), age at diagnosis (continuous), ethnicity, tumour grade, tumour size (continuous), ER-status and PRstatus
9 etable 7. Breast cancer-specific mortality and ipsilateral invasive recurrence rates from DCIS diagnosis among matched DCIS patients treated with lumpectomy alone versus lumpectomy and radiation etable 7a. Breast cancer-specific mortality rates from DCIS diagnosis among matched DCIS patients treated with lumpectomy alone versus lumpectomy and radiation Year Lumpectomy and radiation Lumpectomy alone FU time (years) Events Rate (%) Cumulative Rate (%) FU time (years) Events Rate (%) Cumulative Rate (%) Overall 216, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
10 etable 7b. Ipsilateral invasive recurrence rates from DCIS diagnosis among matched DCIS patients treated with lumpectomy alone versus lumpectomy and radiation Year Lumpectomy and radiation Lumpectomy alone FU time (years) Events Rate (%) Cumulative Rate (%) FU time (years) Events Rate (%) Cumulative Rate (%) Overall 210,819 1, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
11 etable 8. Breast cancer-specific mortality and ipsilateral invasive recurrence rates from DCIS diagnosis among matched DCIS patients treated with mastectomy versus lumpectomy and radiation etable 8a. Breast cancer-specific mortality rates from DCIS diagnosis among matched DCIS patients treated with mastectomy versus lumpectomy and radiation Year Lumpectomy and radiation Mastectomy FU time (years) Events Rate (%) Cumulative Rate (%) FU time (years) Events Rate (%) Cumulative Rate (%) Overall 213, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
12 etable 8b. Ipsilateral invasive recurrence rates from DCIS diagnosis among matched DCIS patients treated with mastectomy versus lumpectomy and radiation Year Lumpectomy and radiation Mastectomy FU time (years) Events Rate (%) Cumulative Rate (%) FU time (years) Events Rate (%) Cumulative Rate (%) Overall 210, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
13 efigure 1. Breast cancer-specific survival post-dcis in propensity-matched patients treated with lumpectomy alone vs. with mastectomy 100.0% 99.5% 99.0% Survival 98.5% 98.0% 97.5% 97.0% Lumpectomy alone Mastectomy p =.43 (log-rank) Years after DCIS diagnosis Number at risk Lumpectomy alone 20,832 13,338 6, Mastectomy 20,832 13,556 6,
14 efigure 2. Ipsilateral invasive recurrence-free survival post-dcis in propensitymatched patients treated with lumpectomy and radiation vs. with lumpectomy alone 100% 98% Survival 96% 94% 92% Lumpectomy alone Lumpectomy and radiation p <.001 (log-rank) 90% Years after DCIS diagnosis Number at risk Lumpectomy alone 29,458 18,339 8,813 1,127 Lumpectomy and radiation 29,465 19,373 9,689 1,248
15 efigure 3. Breast cancer-specific survival post-dcis in propensity-matched patients treated with lumpectomy and radiation vs. with mastectomy 100.0% 99.5% 99.0% Survival 98.5% 98.0% 97.5% 97.0% Lumpectomy and radiation Mastectomy p =.02 (log-rank) Years after DCIS diagnosis Number at risk Lumpectomy and radiation 29,865 18,551 8,735 1,143 Mastectomy 29,865 18,311 8,562 1,131
16 efigure 4. Ipsilateral invasive recurrence-free survival post-dcis in propensitymatched patients treated with lumpectomy and radiation vs. with mastectomy 100% 98% Survival 96% 94% 92% 90% Lumpectomy and radiation Mastectomy p <.001 (log-rank) Years after DCIS diagnosis Number at risk Lumpectomy and radiation 29,864 18,376 8,509 1,080 Mastectomy 29,850 18,209 8,463 1,113
17 efigure 5. Contralateral invasive breast cancer-free survival post-dcis in propensity-matched patients treated with lumpectomy and radiation vs. with lumpectomy alone 100% 98% Survival 96% 94% 92% Lumpectomy alone Lumpectomy and radiation p =.01 (log-rank) 90% Years after DCIS diagnosis Number at risk Lumpectomy alone 29,390 18,428 8,907 1,146 Lumpectomy and radiation 29,411 19,019 9,342 1,186
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