Factors associated with local breast cancer recurrence after mastectomy in the Netherlands: a retrospective nationwide cohort study

Background: Despite presumed complete removal of glandular breast tissue, breast cancer (BC) patients can experience local recurrence (LR) after mastectomy. Most trials report recurrences as locoregional recurrence, potentially obscuring risk factors for LR. In this study, incidence of and risk factors for isolated LR after mastectomy were analysed. Methods: Women diagnosed with primary unilateral nonmetastatic BC treated with mastectomy between 2012 and 2016 were selected from the Netherlands Cancer Registry. LR incidence was assessed within guideline-based indication groups. Multivariable Cox regression models were constructed for patients with and without primary systemic therapy (PST). Results: In total, 17,082 non-PST and 5033 PST patients were included, of whom 345 (2%) and 80 (1.6%) had LR after a median follow-up of 7.8 and 6.7 years, respectively. LR rates were low but varied between indication groups. In the non-PST group, screening detection, low grade, targeted therapy while HER2-positive, radiation therapy (RT), and adjuvant chemotherapy were associated with lower LR risk. Younger age, inner-quadrant location, higher tumour and nodal stage, immediate reconstruction, and omission of endocrine therapy were associated with higher LR risk. In the PST group, pathologic complete response, HER2-positivity, and RT were associated with lower LR risks, while higher clinical T stage, presence of ductal carcinoma in situ, and no endocrine therapy while hormone-receptor positive were associated with higher LR risk. Conclusion: We identified several factors associated with LR rates after mastectomy. Despite the observational character of our study, these factors could be considered in future treatment decision-making.