Mortality After Late Breast Cancer Recurrence in Denmark

Abstract

PURPOSE Late breast cancer (BC) recurrence (ie, ≥ 10 years after primary diagnosis) may have a more favorable prognosis than earlier recurrence. We investigated the risk of BC death after late recurrence, identified prognostic factors, and compared survival after early and late recurrence. METHODS Using the Danish Breast Cancer Group and other nationwide databases, we identified women with early or late BC recurrence during 2004-2018, who were alive 6 months after recurrence. We followed them until BC death, death from other causes, emigration, 10 years, or December 31, 2018, whichever came first. We calculated mortality rates (MRs) per 1,000 person-years (PY) and cumulative BC mortality, for early versus late recurrence, and by characteristics of the primary tumor and the late recurrence. Using Cox regression, we calculated adjusted hazard ratios (HRs) for BC death, accounting for death from other causes as competing risks. RESULTS Among 2,004 patients with late recurrence, 721 died of BC with a median survival time of 10 years (MR = 84.8 per 1,000 PY; 10-year cumulative mortality = 50%). Among 1,528 patients with early recurrence, 1,092 BC deaths occurred with a median survival time of 4 years (MR = 173.9 per 1,000 PY; 10-year cumulative mortality = 72%). We observed a lower hazard of BC-specific death among patients who developed late compared with early recurrence (hazard ratio = 0.72; 95% CI, 0.62 to 0.85). Advanced stage at primary diagnosis, distant metastases, adjuvant treatment for locoregional recurrence, and systemic treatment for distant recurrence were associated with increased mortality after late recurrence. Breast-conserving surgery at primary diagnosis, locoregional recurrence, and surgery for recurrence were associated with lower mortality after late recurrence. CONCLUSION Patients with late recurrence had more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for BC death.

Late Recurrence Following Early Breast Cancer

“…Two contemporary challenges in breast oncology are apparent in these cases: (1) assessing the risk of late recurrence and optimizing adjuvant therapy to prevent late recurrence, plus (2) managing clinically overt distant metastatic breast cancer presenting many years after diagnosis. The report by Pedersen et al 1 that accompanies this article both extends our knowledge of the scope of this challenge and provides insight into survival patterns for patients with early versus late recurrence.…”

“…At present, radiologically detectable or symptomatic distant metastases presenting years after diagnosis remains an important clinical issue, as seen in our second case. The accompanying report by Pedersen et al 1 shows improved survival for late versus early breast cancer recurrence (late recurrence defined in their study as recurrence 10 years from initial diagnosis) from a large single-country data set. Previous smaller reports have similarly found improved survival for those with late recurrence relative to those with early recurrence.…”

Rethinking breast cancer follow-up based on individual risk and recurrence management

“…LRR occurs in 5-15% of cases treated with breast conservative surgery (BCS) plus adjuvant radiotherapy (RT) or mastectomy [27][28][29], and represents an independent poor prognostic factor [4]. The management of LRR requires a multidisciplinary approach [30].…”

“…In patients with HR-positive disease, the annual risk of relapse remains constant at long term, and relapse may occur as late as a decade after the initial diagnosis [3]. Early relapses have a worse prognosis than late ones [4].…”

Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

“…5 For patients with late recurrences, 10-year breast cancer-specific mortality approaches 50%. 6 Although about 6% of patients with breast cancer are diagnosed with de novo metastatic breast cancer, most are diagnosed with earlier-stage disease and treated with curative-intent local and systemic therapy. 7 Of more than 150,000 patients currently living with metastatic breast cancer, approximately three quarters initially presented with early-stage disease.…”