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The distinctive biology of cancer in adolescents and young adults

Key Points

  • The relative lack of progress in treating cancer in adolescents and young adults (AYAs) is in part due to a lack of appreciation of differences in the biology of malignant diseases in this age group relative to younger and older persons.

  • Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of AYAs, including leukaemias, lymphomas, sarcomas, melanoma, and carcinomas of the breast, colon, rectum and nasopharynx.

  • Translational and clinical research should not assume that the biology of cancers and AYA hosts is the same as in other age groups, even if the diseases seem the same clinically and histopathologically.

  • A systematic review of previously reported biological and therapeutic outcomes, that combines older adolescent and young adult patients with younger and older persons, should be made of biological differences if the numbers of subjects or samples permit an adequate assessment.

  • In addition, prospective studies evaluating potential biological differences should be incorporated into investigations that include patients across the age spectrum.

  • Therapeutic strategies tailored to the AYA age group, based on the distinct biology of the cancer and the host, might improve outcomes and prognosis.


One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.

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Figure 1: Relative occurrence of the most common types of cancer in 15–39-year-olds.
Figure 2: Incidence of acute lymphoblastic leukaemia (ALL) as a function of age at diagnosis and gender.
Figure 3: Cancers with 5-year relative survival rates that are lower in adolescents and young adults (AYAs) than in younger or older patients.
Figure 4: Other cancers with 5-year relative survival rates that have different patterns in adolescents and young adults (AYAs) from those in younger or older patients.
Figure 5: Breast cancer survival rates in US women, by age at diagnosis.
Figure 6: Survival by age of diagnosis 1993–1998.
Figure 7: Tumour bank specimens versus incidence of cancer as a function of patient age.


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Author contributions are as follows: Study concept and design: A.B. Acquisition of data: A.B. Analysis and interpretation of data: A.B. Drafting of the manuscript: A.B., R.B. Critical revision of the manuscript for intellectual content: A.B., R.B., B.A., B.H.-L., D.T. and C.E. Statistical expertise: A.B. Obtained funding: A.B. Authors who are independent of any commercial funder and had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis: A.B., R.B., B.A., B.H.-L., D.T. and C.E. Administrative, technical or material support: A.B. Study supervision: A.B. This work was supported by grants from the Aflac Insurance Co., the National Cancer Institute (NCI U10 CA98543) and the Lance Armstrong Foundation. Presented in part at the Roundtable Meeting of the National Cancer Institute Progress Review Group, Denver, Colorado, 24–25 April, 2006. We are indebted to the members of the Children's Oncology Group Adolescent and Young Adult Committee and the Aflac Insurance Co. for their support of and contributions to this investigation. The Biology and Clinical Trials Subgroups of the US National Cancer Institute Progress Review Group in Adolescent and Young Adult Oncology are M. Tewari, L. Balducci, C. Bloomfield, W. Carroll, D. Colaizzi, Robert Comis, G. D'Amato, M. Foti, J. Goldberg, D. Hawkins, M. L. Keohan, M. Link, C. Love, B. Rubin, P. Shaw, C. Somkin, W. Stock, J. Summers, D. Sussman, S. Wells, J. Whelan and B. Williams.

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Correspondence to Archie Bleyer.

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acute lymphoblastic leukaemia

acute myeloid leukaemia

bladder cancer

brain tumour

breast cancer

cervical cancer

chronic myeloid leukaemia

colorectal cancer

endometrial cancer

Ewing sarcoma

gastrointestinal stromal tumour

Hodgkin lymphoma

Kaposi sarcoma

kidney cancer


liver cancer




ovarian cancer

pancreatic cancer

prostate cancer





testicular cancer

thyroid carcinoma

Wilms tumour

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Progress Review Group

(PRG). Panel of experts assembled by the US National Cancer Institute to assess the state of the science of a cancer or cancer group and make recommendations for future research.

Microsatellite instability

A condition manifested by damaged DNA due to defects in the normal DNA repair process and characterized by unstable sequences of repeating units of 1–4 base pairs in length.

Familial adenomatous polyposis

An inherited mutation in the APC or MUTYH gene results in numerous polyps in the large intestine that usually undergo malignant transformation into colon cancer when not treated.

Hereditary non-polyposis colon cancer

(HNPCC). Colon cancer emanating from inherited mutations known as Lynch syndrome that prevent self-repair capability of DNA and also increase risk of stomach, small intestine, liver, uterus, ovary, brain and skin cancer.

L2 morphology

A French–American–British (FAB) system histological type of leukaemic lymphoblast characterized by larger and more variable size, more cytoplasm and a worse prognosis than the L1 type.

Borderline tumour

Tumours of the ovary with epithelial (carcinoma) and stromal (non-epithelial) elements that are histologically of an intermediate grade between benign and malignant and of uncertain malignant potential.

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Bleyer, A., Barr, R., Hayes-Lattin, B. et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer 8, 288–298 (2008).

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