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

SIMPLE SUMMARY: Epidemiologic studies have observed higher risks of breast cancer recurrence and death in women diagnosed <40 years of age compared to ≥40 years. There is ongoing clinical debate as to whether this is due to the overrepresentation of advanced and aggressive disease features or unique disease biology. Younger women are more likely to be diagnosed with more aggressive subtypes, including triple-negative breast cancer. Herein, we conduct a systematic review and meta-analysis of studies assessing the association between age <40 years at diagnosis and clinical outcomes in triple-negative breast cancer. We present pooled risk estimates for recurrence-free survival, breast cancer-specific and overall survival, and pathological complete response. Our findings highlight the prognostic significance of age in triple-negative breast cancer and may point to a need for tailored local and systemic treatment strategies in women of younger ages. 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.