Outcomes After Sentinel Lymph Node Biopsy and Radiotherapy in Older Women With Early-Stage, Estrogen Receptor-Positive Breast Cancer

Abstract

Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published.

Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer.

Design, setting, and participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system.

Exposures: Sentinel lymph node biopsy and adjuvant RT.

Main outcomes and measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs).

Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%).

Conclusions and relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Beriwal reported receiving consulting fees from Varian and Elsevier and serving on the data safety monitoring board of Xoft. Dr Diego reported serving on the data safety monitoring board of Xoft. Dr Brufsky reported receiving personal fees from AstraZeneca, Lilly, Novartis, Roche, and Pfizer outside the submitted work. Dr Ferris reported receiving consulting fees from Aduro Biotech, clinical trial research funding from AstraZeneca/MedImmune; serving on the advisory board of Bristol Myers Squibb, and MacroGenecs, Numab Therapeutics, and Pfizer; clinical trial research funding from the EMD Serono advisory board and the Merck advisory board; stock, research funding, and consulting fees from Novasenta, Sanofi, and Zymeworks; and research funding from Tesaro. Dr Emens reported being an employee of University of Pittsburgh and UPMC University of Pittsburgh Physicians; receiving grants from HeritX Inc, National Surgical Adjuvant Breast and Bowel Project Foundation, Translational Breast Cancer Research Consortium, Breast Cancer Research Foundation, National Cancer Institute, US Department of Defense, Stand Up to Cancer, Johns Hopkins University, University of California San Francisco, Cornell University, Dana Farber Cancer Institute, Aduro Biotech, Astrazeneca, Bolt Therapeutics, Bristol Myers Squibb, Corvus, EMD Serono, Genentech, Roche, Maxcyte, Merck, Silverback, Tempest, Takeda, CytomX, and Compugen; receiving publication support from Genentech; receiving nonfinancial support from Aduro Biotech for preclinical studies; receiving in-kind materials for preclinical studies from Maxcyte; receiving travel support from Genentech, Roche, Amgen, Macrogenics, Replimune, Vaccinex, and Bristol Myers Squibb; receiving consulting fees from Genentech, Roche, Macrogenics, Replimune, Vaccinex, Syntax, Abbvie, Astrazeneca, Medimmune, Bayer, GCPR, Gilead, Gritstone, Novartis, Peregrine, Shionogi, and Chugai outside the submitted work; holding a patent for Aduro Biotech with royalties paid and a patent for Elsevier with royalties paid; and serving as vice president for Society for Immunotherapy of Cancer and as a former at-large member of the Society for Immunotherapy of Cancer board of directors. No other disclosures were reported.

Figures

Figure 1.. Rates of Sentinel Lymph Node Biopsy (SLNB) and Radiotherapy (RT) Use, 2010-2018

Use rate was calculated as a percentage of patients who underwent SLNB or RT over the total number of patients who did not undergo axillary staging or RT. A, The vertical dashed line at 2016 indicates the adoption by the Society of Surgical Oncology of the Choosing Wisely guideline. The P values for patients who received SLNB were P = .09 for those younger than 70 years and P = .49 for those aged 70 years or older. B, Limited data were available for 2018. The P values for patients who received RT were P = .27 for those younger than 70 years and P = .04 for those aged 70 years or older.

Figure 2.. Sankey Diagrams of Treatment and Pathological Relationships in the Study Cohort

Panels should be read from left to right. A, Of the whole cohort of 2109 patients, 736 did not undergo sentinel lymph node biopsy (SLNB) but 1373 patients received it. Furthermore, of the 1373 patients who received SLNB, 1214 were deemed pathologically node negative (pN0) and 159 were deemed pathologically node positive (pN+). pNX indicates unknown pathological nodal status in patients who did not receive SLNB. B, Breast operation included lumpectomy, mastectomy, or no surgery, and subsequent adjuvant treatments included radiotherapy (RT), endocrine therapy, and chemotherapy (CTx).

Figure 3.. Kaplan-Meier Recurrence-Free Survival Estimates of Patients Who Underwent Sentinel Lymph Node Biopsy (SLNB) and Radiotherapy (RT) in the Propensity Score–Matched Cohorts

Patients who did not die and were lost to follow-up within the observation period were censored at their date of last contact. DFS indicates disease free survival; LRFS, locoregional recurrence-free survival.