The Association between Early-Onset Diagnosis and Clinical Outcomes in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

Early-onset diagnosis, defined by age <40 years, has historically been associated with inferior outcomes in breast cancer. Recent evidence suggests that this association is modified by molecular subtype. We performed a systematic review and meta-analysis of the literature to synthesize evidence on the association between early-onset diagnosis and clinical outcomes in triple-negative breast cancer (TNBC). Studies comparing the risk of clinical outcomes in non-metastatic TNBC between early-onset patients and later-onset patients (≥40 years) were queried in Medline and EMBASE from inception to February 2023. Separate meta-analyses were performed for breast cancer specific survival (BCSS), overall survival (OS), and disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and pathological complete response (pCR). In total, 7581 unique records were identified, and 36 studies satisfied inclusion criteria. The pooled risk of any recurrence was significantly greater in early-onset patients compared to later-onset patients. Better BCSS and OS were observed in early-onset patients relative to later-onset patients aged >60 years. The pooled odds of achieving pCR were significantly higher in early-onset patients. Future studies should evaluate the role of locoregional management of TNBC and the implementation of novel therapies such as PARP inhibitors in real-world settings, and whether they improve outcomes.

Keywords: breast cancer-specific survival; early-onset breast cancer; meta-analysis; overall survival; pathological complete response; recurrence-free survival; systematic review; triple-negative breast cancer; young age.

Figure 1

PRISMA flow diagram of included and excluded studies based on eligibility criteria [22].

Figure 2

Forest plot for meta-analysis of disease-free survival. Hazard ratios less than 1 show favourable outcomes in early-onset age group; hazard ratios greater than 1 show poorer outcomes in early-onset age group. References [20,21,23,28,29,31,33,34,35,36,37,41,42,44,45,46,47,49,51,52]. Abbreviations: CI = confidence interval; HR = hazard ratio.

Figure 3

Forest plot for meta-analysis of locoregional and distant recurrence-free survival. Hazard ratios less than 1 show favourable outcomes in early-onset age group; hazard ratios greater than 1 show poorer outcomes in early-onset age group. References [19,20,31,33,34,36,37,38,42,45,47,49]. Abbreviations: CI = confidence interval; HR = hazard ratio.

Figure 4

Forest plot for meta-analysis of breast cancer-specific survival. Hazard ratios less than 1 show favourable outcomes in early-onset age group; hazard ratios greater than 1 show poorer outcomes in early-onset age group. References [13,22,25,27,29,30,33,40,42,48,49]. Abbreviations: CI = confidence interval; HR = hazard ratio.

Figure 5

Forest plot for meta-analysis of overall survival. Hazard ratios less than 1 show favourable outcomes in early-onset age group; hazard ratios greater than 1 show poorer outcomes in early-onset age group. References [18,20,22,28,32,34,37,39,40,41,44,45,46,47,48]. Abbreviations: CI = confidence interval; HR = hazard ratio.

Figure 6

Forest plot for meta-analysis of pathological complete response (pCR). Odds ratios less than 1 show lower odds of achieving pCR in early-onset age group; Odds ratios greater than 1 show higher odds of achieving pCR in early-onset age group. References [24,26,37,43,44,45]. Abbreviations: CI = confidence interval; OR = odds ratio.