P4-11-08: Changes in the Distribution of Loco-Regional and Distant Breast Cancer Recurrences over the Last 20 Years: Implications for Patient Care and Future Research.

Abstract

Abstract Introduction: Improvements in adjuvant therapy have led to a sustained fall in recurrences after early breast cancer. The differential reduction of both local-regional and systemic recurrences is poorly understood. This study aimed to explore changes in the distribution of loco-regional and distant recurrences in clinical trials reported over the last 20 years. We also aimed to determine the relative impact of adjuvant chemotherapy and endocrine therapy. Methods: A MEDLINE search for adjuvant, Phase III randomized breast cancer clinical studies between January 1990 and March 2011 was performed. Neo-adjuvant, single agent biologics and studies that did not report the proportion of loco-regional and distant recurrences were excluded. Change in the frequency of recurrences was assessed as the non-parametric correlation between the number of loco-regional recurrences (as a proportion of all recurrences) and time. Studies were weighted by sample size. Pre-specified subgroup analyses were assessed using the interaction test and included type of surgery performed, radiotherapy use, menopausal status and type of systemic therapy delivered. Definition of local and distant recurrences differed between studies. For consistency, loco-regional recurrences were classified as recurrences limited to the ipsilateral breast, chest wall, axillary, supraclavicular and internal mammary lymph nodes. Any other recurrence was defined as distant, with the exception of contralateral breast cancer; that was excluded from this analysis. Results: Fifty-three randomized clinical trials with a total of 86,598 patients were included in the analysis. Between 1990 and 2011, the proportion of loco-regional recurrences has decreased from approximately 50% to 10% (Spearman's rho = −0.40, p<.001). There was no interaction between type of surgery (mastectomy vs. lumpectomy, p=0.40), adjuvant radiotherapy use (p=0.63) and menopausal status (p=0.95) and the correlation of loco-regional recurrences and time. Chemotherapy use showed a larger negative correlation compared with endocrine therapy (rho = 0.49 vs rho = 0.24, p=0.008). Conclusion: Advances in treatment of early breast cancer have differentially reduced the proportion of loco-regional recurrences compared with distant recurrences. In recent trials, loco-regional recurrences account for less than 10–15% of all recurrences. These falling event rates may affect patient care, especially when deciding on treatments influencing loco-regional control. This change may also impact on the design of clinical trials assessing loco-regional therapy such as surgery and/or local radiation therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-08.