Abstract

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.

Highlights

  • IMPORTANCE Cohort studies show better survival after breast-conserving surgery (BCS) with postoperative radiotherapy (RT) than after mastectomy (Mx) without RT

  • S ince the publication of key trials[1,2] confirming the oncological equivalence of breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) and mastectomy (Mx), BCS is recommended for patients with early breast cancer

  • It is important to consider that RT is indicated after BCS: in Sweden, postmastectomy RT is recommended for T3 tumors and extensive tumor multifocality as well as in nodepositive disease, with few exceptions

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Summary

Methods

This cohort study used prospectively collected data from the Swedish National Breast Cancer Register (NKBC), with national coverage since 1992 and harmonized online reporting since 2008. Overall and breast cancer–specific mortality rates were modeled and adjusted using Cox regression, with time since surgery as the underlying timescale. Associations between locoregional treatment (BCS+RT, Mx-RT, and Mx+RT) and mortality rates are reported as hazard ratios (HRs) with 95% CIs. First, models were stepwise adjusted for confounders (age, year, region, prognostic group, Nottingham grade, subtype, socioeconomic factors, and CCI). HRs for locoregional treatment were estimated for short (0-5 years) and long (>5 years) follow-up separately. We assessed a model with a time-varying effect of CCI as a sensitivity analysis, the results of the exposure variable of interest (locoregional treatment); this remained unchanged to the second decimal. The final model used in the main analysis did not include time-varying effects in CCI. All statistical analyses were performed using R, version 4.0.1 (R Foundation)

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