. Author manuscript; available in PMC: 2023 Oct 1.

Published in final edited form as: Nat Rev Clin Oncol. 2022 Sep 6;19(10):656–673. doi: 10.1038/s41571-022-00672-8

Table 2.

Clinical and tumour-specific characteristics of early-onset versus later-onset cancers

Cancer type	Clinical characteristics	Tumour characteristics
Breast cancer	Advanced disease stages at diagnosis, inferior OS^{261, 263, 265, 339–342}	Adverse pathological features, including high tumour grade, triple-negative (ESR1 (also known as ER)-negative, PGR (also known as PR)-negative, ERBB2 (also known as HER2)-negative) subtype, ERBB2 (HER-2)-positive subtype, and MKI67 (Ki-67) overexpression.^261–269
CRC	Predilection to rectal and distal localization within the colon, advanced disease stages at diagnosis, inferior OS^{94, 187, 270, 271, 276, 280, 343–358}	Aggressive tumour phenotypes (excluding MSI-high status) such as poor differentiation, lymphovascular and perineural invasion, signet ring cell histology, LINE-1 hypomethylation, and lower lymphocytic immune reaction.^{190, 273–282}
Endometrial cancer	Inconsistent findings on OS and disease stages at diagnosis^{196, 283–289}	Certain studies suggest that early-onset endometrial cancer is associated with favourable features, such as well-differentiated carcinoma and adenoacanthoma^283–287; whereas, others suggest that early-onset endometrial cancer is associated with unfavourable pathological features, including poor differentiation, high mitotic rates, and deep myometrial invasion.^{196, 288, 289}
Multiple myeloma	–	Certain studies suggest that younger patients have greater numbers of lytic lesions and high-risk cytogenetic abnormalities^{290, 291}; whereas, other studies suggest that younger patients have similar or more-favourable tumour characteristics.^{291, 293, 294}
Pancreatic cancer	Advanced disease stages at diagnosis^{297, 298}	Poor differentiation, perineural invasion.^{228, 295–298}
Prostate cancer	Metastatic disease, resistance to androgen-deprivation therapy, and shorter OS^299–302	Genomic and epigenomic aberrations seen in patients with early-onset prostate cancer might be distinctly different to those seen in patients with later-onset disease^{303, 304}; for example, clinically-advanced early-onset prostate cancers might be associated with TMPRSS2::ERG fusions and fewer AR, SPOP and ASXL1 alterations.³⁰⁵
Stomach cancer	More common in women, advanced disease stages at diagnosis^299–302	Higher grades, advanced disease stages, signet ring cell or diffuse histology^{246, 253, 306}; fewer somatic mutations in TP53 and more somatic mutations in MUC5B, BANP, CDH1, and TGFBR1.^{307, 308}

CRC, colorectal cancer; LINE-1, long interspersed nucleotide element-1; MSI, microsatellite instability; OS, overall survival.