Cohort studies show better survival after breast-conserving surgery (BCS) with postoperative radiotherapy (RT) than after mastectomy (Mx) without RT. It remains unclear whether this is an independent effect or a consequence of selection bias.
To determine whether the reported survival benefit of breast conservation is eliminated by adjustment for 2 pivotal confounders, comorbidity and socioeconomic status.
Cohort study using prospectively collected national data. Swedish public health care; nationwide clinical data from the National Breast Cancer Quality Register, comorbidity data from Patient Registers at the National Board of Health and Welfare, and individual-level education and income data from Statistics Sweden. The cohort included all women diagnosed as having primary invasive T1-2 N0-2 breast cancer and undergoing breast surgery in Sweden from 2008 to 2017. Data were analyzed between August 19, 2020, and November 12, 2020.
Locoregional treatment comparing 3 groups: breast-conserving surgery with radiotherapy (BCS+RT), mastectomy without radiotherapy (Mx-RT), and mastectomy with radiotherapy (Mx+RT).
Overall survival (OS) and breast cancer-specific survival (BCSS). Main outcomes were determined before initiation of data retrieval.
Among 48 986 women, 29 367 (59.9%) had BCS+RT, 12413 (25.3%) had Mx-RT, and 7206 (14.7%) had Mx+RT. Median follow-up was 6.28 years (range, 0.01-11.70). All-cause death occurred in 6573 cases, with death caused by breast cancer in 2313 cases; 5-year OS was 91.1% (95% CI, 90.8-91.3) and BCSS was 96.3% (95% CI, 96.1-96.4). Apart from expected differences in clinical parameters, women receiving Mx-RT were older, had a lower level of education, and lower income. Both Mx groups had a higher comorbidity burden irrespective of RT. After stepwise adjustment for all covariates, OS and BCSS were significantly worse after Mx-RT (hazard ratio [HR], 1.79; 95% CI, 1.66-1.92 and HR, 1.66; 95% CI, 1.45-1.90, respectively) and Mx+RT (HR, 1.24; 95% CI, 1.13-1.37 and HR, 1.26; 95% CI, 1.08-1.46, respectively) than after BCS+RT.
Despite adjustment for previously unmeasured confounders, BCS+RT yielded better survival than Mx irrespective of RT. If both interventions are valid options, mastectomy should not be regarded as equal to breast conservation.

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