Even after adjusting for comorbidities, socioeconomic status, BCS is effective, safe

Overall survival (OS) and breast cancer-specific survival (BCSS) were better in women with early-stage breast cancer who underwent breast-conserving surgery followed by radiotherapy than those who had mastectomy with or without radiotherapy, according to results from a study published in JAMA Surgery.

Specifically, researchers found that patients undergoing BCS had significantly higher five-year overall survival (95.1%) and BCSS (98.2%) compared with women undergoing mastectomy regardless of whether they had post-mastectomy radiation. In women who underwent post-mastectomy radiation, five-year OS was 86.0% and BCSS was 90.5%, while in mastectomy patients they were 84.5% and 95.0%, respectively.

Jana de Boniface, PhD, of the Department of Surgery, Capio St. Göran’s Hospital, Stockholm, Sweden, and colleagues, put forth the rationale behind their study: “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.”

In addition, several key factors are also known to play a role in breast cancer survival, they noted.

“There are complex interactions between breast cancer survival, socioeconomic status, and comorbidity. Individuals with a lower socioeconomic status present with more advanced disease, have a lower adherence to mammography screening, are less likely to receive chemotherapy, and have inferior survival rates. In addition, lifestyle factors increasing cancer risk and impacting survival, such as obesity and smoking, are more common in socioeconomically deprived groups, in addition to comorbidities that negatively affect completion rates of systemic therapy,” wrote de Boniface and fellow researchers.

“To further dissect the association of locoregional treatment with survival, this large population-based cohort study investigates the association of socioeconomic factors and comorbidity with overall and breast cancer–specific survival after BCS with RT, Mx with, and Mx without postoperative RT,” they added.

These researchers prospectively collected Swedish national data form the National Breast Cancer Quality Register (clinical data), the Patient Registers at the National Board of Health and Welfare (comorbidity data), and Statistics Sweden (individual-level education and income data) from all women with a diagnosis of primary invasive T1-2 NO-2 breast cancer who underwent breast surgery from 2008-2017.

After a median follow-up of 6.28 years, they compared overall survival (OS) and breast cancer-specific survival (BCSS) in women classified into three groups: breast-conserving surgery with radiotherapy (BCS+RT; 59%), mastectomy without radiotherapy (Mx-RT; 25.3%), and mastectomy with radiotherapy (Mx+RT; 14.7%).

All-cause death occurred in 6,573 women, and breast cancer-specific death in 2,313. The five-year OS was 91.1% (95% CI: 90.8-91.3) and BCSS was 96.3% (95% CI: 96.1-96.4).

Women treated with Mx-RT tended to be older, with lower education and income levels. Women in both Mx treatment groups had a higher burden of comorbidity.

Upon adjustment for all covariates and compared with women treated with BCS+RT, women treated with Mx-RT had significantly worse OS (HR: 1.79; 95% CI: 1.66-1.92) and BCSS (HR: 1.66; 95% CI: 1.45-1.90), as did women treated with Mx+RT (HR: 1.24; 95% CI: 1.13-1.37 and HR: 1.26; 95% CI: 1.08-1.46, respectively).

“In conclusion, this report adds evidence to support the recommended use of BCS with RT in both node-negative and node-positive breast cancer. Neither socioeconomic background and comorbidity nor the addition of postoperative RT after mastectomy diminished survival differences. This report casts additional doubt on the practice to offer mastectomy to patients who are suitable candidates for breast conservation,” concluded de Boniface et al. According to Lisa A. Newman, MD, MPH, of the Department of Surgery, Weill Cornell Medicine, New York City, “The study by de Boniface et al features fascinating results that challenge the wisdom of prematurely abandoning radiation after BCS for clinically early-stage disease.”

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In her accompanying editorial, Newman presented the differing approaches to interpreting these results.

“On one hand, we may be seeing evidence supporting the hypothesis that radiation induces secondary abscopal antitumor effects. This study did not include patients treated by lumpectomy alone, but the superior survival in BCS patients who have undergone radiation nonetheless begs the question of whether breast radiation confers an outcome advantage beyond local control. Any independent survival effect of radiation after mastectomy cannot be assessed from this study because nearly all node-positive patients received regional radiation,” she wrote.

“On the other hand, it has also been argued that some breast cancers are so biologically indolent that they do not warrant any locoregional intervention. It is possible that the disproportionately high frequency of T1 and hormone receptor– positive/ERBB2-negative tumors in the BCS compared with mastectomy subsets included a significant subset of potentially overtreated cases within the BCS group,” Newman added.

“Regardless of the interpretation chosen for the outcome patterns observed in this study, one fact cannot be disputed: BCS is safe and effective management in early-stage breast cancer,” she concluded.

Limitations of this study include the lack of potential confounders (smoking, BMI), the possible underestimation of unlisted comorbid conditions, and short follow-up.

  1. Breast conservation offers women with early-stage breast cancer a survival benefit independent of measured confounders and should be given priority if both breast conservation and mastectomy are valid options.

  2. Breast-conserving surgery plus radiotherapy yielded better survival for women with breast cancer than mastectomy regardless of further radiotherapy.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

This study was funded by the Swedish Breast Cancer Association. de Boniface is supported by a Junior Clinical Investigator Award from the Swedish Cancer Society.

de Boniface and Newman reported no conflicts of interest.

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