Study Investigates the Risk of Breast Cancer Mortality After Late Breast Cancer Recurrence

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In a Danish study reported in the Journal of Clinical Oncology, Pedersen et al identified risk of breast cancer mortality among women with breast cancer recurrence at ≥ 10 years after primary diagnosis and found that mortality risk was reduced after late vs early recurrence.

Study Details

The study involved data from the Danish Breast Cancer Group and other nationwide databases on women with early (< 10 years after primary diagnosis) or late (≥ 10 years after primary diagnosis) breast cancer recurrence between 2004 and 2018 who were alive 6 months after recurrence. Patients were followed until either breast cancer death, death from other causes, emigration, 10 years, or end of December 2018—whichever occurred first. Mortality rates per 1,000 person-years and cumulative breast cancer mortality were calculated. Cox regression was used to determine hazard ratios (HRs) for breast cancer death, accounting for death from other causes as a competing risk.

Key Findings

Among 2,004 patients with late recurrence, 721 died of breast cancer, with a median breast cancer–specific survival of 10 years from 6 months after recurrence. The breast cancer–specific mortality rate was 84.8 (95% confidence interval [CI] = 78.8–91.2) per 1,000 person-years. Cumulative breast cancer­–specific mortality at 2, 5, and 10 years after recurrence was 11%, 32%, and 50%, respectively.

Among 1,528 patients with early recurrence, 1,092 died of breast cancer, with a median breast cancer–specific survival time of 4 years. The breast cancer–specific mortality rate was 173.9 (95% CI = 163.9–184.5) per 1,000 person-years. Cumulative breast cancer–specific mortality 2, 5, and 10 years after recurrence was 27%, 58%, and 72%, respectively.

In analysis adjusted for calendar year at primary diagnosis; stage of primary breast cancer; grade of primary breast cancer; surgery type of primary breast cancer; allocation to chemotherapy and/or endocrine therapy at primary breast cancer comorbidity at recurrence; age at recurrence; calendar year of recurrence; estrogen receptor status; HER2 status at recurrence; treatment of recurrence (radiation therapy, chemotherapy, and surgery); and extent of recurrent disease, risk of breast cancer–specific death was lower for late vs early recurrence (HR = 0.72, 95% CI = 0.62–0.85). Hazard ratios were 0.47 (95% CI = 0.30–0.75) for late vs early locoregional recurrence and 0.82 (95% CI = 0.66–1.02) for late vs early distant recurrence.

Among patients with late recurrence, risk of breast cancer–specific death was increased among patients with distant vs locoregional recurrence (HR = 1.69, 95% CI = 1.26–2.26) and those who received chemotherapy (HR = 2.03, 95% CI = 1.68–2.46) or radiation therapy (HR = 1.92, 95% CI = 1.60–2.30) for recurrence. Advanced stage at primary diagnosis was also associated with increased risk, whereas additional factors associated with reduced risk were breast-conserving surgery at primary diagnosis and surgery for recurrence.

The investigators concluded, “Patients with late recurrence had more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for breast cancer death.”

Deirdre P. Cronin-Fenton, PhD, of Aarhus University and Aarhus University Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the Danish Cancer Society. For full disclosures of the study authors, visit

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