Associations between axillary staging, adjuvant treatment, and survival in older women with early-stage breast cancer: A population-based study.
Authors: Castelo Matthew , Sutradhar Rinku , Faught Neil , Giffoni M. M. Mata Danilo , Hahn Ezra , Nguyen Lena , Paszat Lawrence Frank , Rodin Danielle , Trebinjac Sabina , Rakovitch Eileen 
Published: June 2022

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Background: The Choosing Wisely guidelines recommend against surgical axillary staging (AS) in women ≥70 years with ER+/HER2- early stage breast cancer (BC). However, there has been little change in practice patterns, which may be influenced by observational studies reporting worse survival among women not receiving AS. Previous analyses did not take into account comorbidities, specific adjuvant treatments and HER2 status which may confound the association between AS omission and survival. This study examined the impact of AS omission on survival in older patients with Stage I/II BC, and secondarily emulated the Choosing Wisely population in a subgroup of those ≥70 years undergoing sentinel node biopsy (SLNB) vs. no AS for ER+/HER2- tumors. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women aged 65-95 years who underwent surgery for Stage I/II BC between 2010 and 2016. We excluded women who received neoadjuvant chemotherapy. To address confounding between those who did and did not receive AS, we built a propensity score model including patient and disease characteristics. Patients were weighted by propensity scores using overlap weights. Association with overall survival (OS) was calculated using weighted Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using weighted Fine and Gray models, adjusting for biomarkers and adjuvant treatments. Adjuvant treatment receipt was modelled with weighted log-binomial models. Results: Among 17,546 older women, 1,807 (10.3%) did not undergo AS, who were older, more comorbid, less likely to undergo mastectomy, and more likely to have tumors ≥ 2 cm. After propensity score weighting, baseline characteristics including comorbidity were balanced between the two groups. Women who did not undergo AS were less likely to receive adjuvant chemotherapy (adjusted RR 0.70. 95% CI 0.58-0.84), endocrine therapy (adjusted RR 0.85, 95% CI 0.82-0.89) and radiotherapy (adjusted RR 0.69, 95% CI 0.65-0.73). Unadjusted 5-year survival was lower for women who did not undergo AS (68.1%, 95% CI 65.8-70.2 vs. 87.6%, 95% CI 87.0-88.1; p< 0.001), and there was a higher 5-year incidence of BC deaths (7.6%, 95% CI 6.2-9.2 vs. 4.3%, 95% CI 3.9-4.7; p< 0.001). After weighting and adjustment, women who did not undergo AS continued to have worse OS (adjusted HR 1.13, 95% CI 1.03-1.24), however, there was no significant difference in BCSS (adjusted HR 1.00, 95% CI 0.78-1.26). The results among 6,286 ER+/HER2- women ≥70 years undergoing SLNB vs. no AS were similar for OS (adjusted HR 1.22, 95% CI 1.05-1.42) and BCSS (adjusted HR 1.08, 95% CI 0.67-1.76). Conclusions: The omission of AS in older women with early stage BC was associated with worse OS, reflecting selection bias, but no significant difference in BCSS.