Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review

Abstract

Background: Metastatic breast cancer (MBC) treatment has changed substantially over time, but we do not know whether survival post-metastasis has improved at the population level.

Methods: We searched for studies of MBC patients that reported survival after metastasis in at least two time periods between 1970 and the present. We used meta-regression models to test for survival improvement over time in four disease groups: recurrent, recurrent estrogen (ER)-positive, recurrent ER-negative, and de novo stage IV. We performed sensitivity analyses based on bias in some studies that could lead earlier cohorts to include more aggressive cancers.

Results: There were 15 studies of recurrent MBC (N = 18 678 patients; 3073 ER-positive and 1239 ER-negative); meta-regression showed no survival improvement among patients recurring between 1980 and 1990, but median survival increased from 21 (95% confidence interval [CI] = 18 to 25) months to 38 (95% CI = 31 to 47) months from 1990 to 2010. For ER-positive MBC patients, median survival increased during 1990-2010 from 32 (95% CI = 23 to 43) to 57 (95% CI = 37 to 87) months, and for ER-negative MBC patients from 14 (95% CI = 11 to 19) to 33 (95% CI = 21 to 51) months. Among eight studies (N = 35 831) of de novo stage IV MBC, median survival increased during 1990-2010 from 20 (95% CI = 16 to 24) to 31 (95% CI = 24 to 39) months. Results did not change in sensitivity analyses.

Conclusion: By bridging studies over time, we demonstrated improvements in survival for recurrent and de novo stage IV MBC overall and across ER-defined subtypes since 1990. These results can inform patient-doctor discussions about MBC prognosis and therapy.

Figure 1.

Study selection.

Figure 2.

Timeline diagram of breast cancer therapies. Bold font indicates that an overall survival benefit was reported in a randomized clinical trial or meta-analysis; italic font indicates that a progression-free survival (but no overall survival) benefit was reported in a randomized clinical trial or meta-analysis; and plain font indicates that no overall survival benefit nor progression-free survival benefit has been reported. Year of introduction is date of Food and Drug Administration (FDA) approval or, for drugs that are not FDA approved to treat breast cancer (vinorelbine, liposomal doxorubicin, platinums), the date of the first major publication that led to widespread use. Dashed arrows show the transition of each therapy from the metastatic setting, where nearly all were originally introduced, to the early-stage setting.

Figure 3.

Meta-regression of the improvement in median survival after breast cancer metastasis over time in (A) recurrent disease, (B) estrogen receptor (ER)-positive recurrent disease, (C) ER-negative recurrent disease, and (D) de novo stage IV disease. In A–C), open triangles indicate studies that included only distant recurrence, and closed circles indicate studies that included locoregional recurrence. Each study is represented by a different color.