Tumors in Adolescents and Young Adults

E. Beghi, G. Logroscino

• Publisher: S. Karger
• Year: 2016
• ISBN:
  9783318059120
• Topic: Medicine
• Subtopic: Gynecology, Obstetrics & Midwifery

The field of adolescents and young adult (AYA) oncology is experiencing a very challenging time. This book is a guide to the key issues for any clinician and health professional managing AYA with cancer in Europe. Emphasis is on collaboration between adult and pediatric specialists. Authors present their perception of the current state of the most prominent primary issues in AYA oncology. Chapters cover cross-cutting issues such as disease epidemiology, systems of care, access to innovative therapy and late effects of treatment and survivorship for AYA-onset cancers. There are discussions of the latest developments and the most important cancer types for AYA, including the shared perspectives of adult and pediatric specialists. Throughout the book recurrent challenges to the AYA community are exposed and solutions proposed. Tumors in Adolescents and Young Adults is highly recommended to any oncologist or haematologist treating patients aged 15 to 39 diagnosed with cancer. It will also be of interest to other members of the multidisciplinary teams involved with this patient group.

Specific Illnesses

Stark DP, Vassal G (eds): Tumors in Adolescents and Young Adults.
Prog Tumor Res. Basel, Karger, 2016, vol 43, pp 64-73 (DOI: 10.1159/000447072)

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Adult Cancers in Adolescents and Young Adults

Valérie Laurence^a · Maria Marples^b · Daniel P. Stark^c

^aAdolescents and Young Adults Unit, Medical Oncology and Pediatric-Adolescents Young Adults Departments, Institut Curie, Paris, France; ^bSt. James’s Institute of Oncology, Leeds, and ^cInstitute of Cancer and Pathology, St. James’s University Hospital, University of Leeds, Leeds, UK

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Abstract

The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials. Here, we discuss the management of AYAs with 3 of the most common cancers affecting adults, when they emerge in the AYA populations, and therefore are currently met by medical oncologists - breast cancer, colorectal cancer and melanoma.

© 2016 S. Karger AG, Basel

Introduction

The epidemiology of ‘adult cancer’ in this population depends on what is the age range considered as adolescents and young adults (AYAs): 15-25 years in the European Network for Cancer Research in Children and Adolescents’ project called European Network for Teenagers and Young Adults with Cancer, 15-39 in the US National Cancer Institute Program and 15-29 in the National Canadian Program.

However, adult-type cancers are an exception in children <15 years, appear in the AYA population and has become the leading cause of cancer in the 20-29 years age range with the emergence of epithelial tumors, melanoma and thyroid cancer [1, 2].

Given the epidemiologic data in the chapter by Desandes and Stark [this vol., pp. 1-15], several adult-type cancers with a young adult onset and therefore possibly encountered by oncologists in their general practice will be discussed: breast cancer, colon cancer and melanoma.

Breast Cancer

Even though it is very rare in adolescents and young women compared to older age groups, with its high incidence in women in general, breast cancer is the leading cause of cancer in young women between 20 and 29. Breast cancer incidence rises steadily with age and, after stabilization, decreases beyond 80 years. The literature about breast cancer in ‘young women’ is huge (2,526 papers in the last 5 years), but has large variations in definitions of ‘young’: <35 years, <40 years and premenopausal. However, less than 1% of breast cancers appear in patients <30 years and 2.7% in patients <35 years, with an estimated incidence of less than 0.1 cases per 100,000 in women <20 years, 1.4 for women of 20-24 years, 8.1 for women of 25-29 years and 24.8 for women of 30-34 years (Seer.gov.org/publications). African American/black young women of 15-39 years have a higher incidence than other ethnic groups [3].

Risk factors for breast cancer in the general population of women <40 years are: higher body mass, use of oral contraceptive and family history of breast cancer. There is a protective effect of breastfeeding [4]. Therapeutic, occupational or wartime radiation exposure are risk factors for breast cancer, depending on age at radiation, time since radiation and radiation dose. In AYAs, this risk is highly relevant. It is a well-established breast cancer risk factor for young women treated for Hodgkin’s lymphoma (HL) who received mantle and/or axillary lymph node radiation, especially for those treated during puberty; after a latency, the risk of breast carcinoma was 75-fold higher in the Bhatia study published in 1996, with an actuarial cumulative likelihood of breast cancer reaching 35% at 40 years; this level of risk is still observed for patients treated in the modern era [5, 6]. Therefore, current guidelines recommend breast cancer screening in female cancer survivors of HL, beginning 8-10 years after the end of treatment, with clinical follow-up and imaging follow-up with mammography and MRI [7, 8]. Genetic predispositions are the other risk factors in the AYA population. Carriers of BRCA1/BRCA2 mutations have a cumulative risk breast cancer estimated at 15-18% for a woman of 25 years of age [8]. Recommendations are that breast awareness starts at 20 years with 6 monthly clinical examination, and at 30 years MRI, mammography ± ultrasound (Institut Curie guidelines, http://www.cancersdusein.curie.fr/sites/default/files//RéférentielFAR-IC-GR-Aout2013.pdf), with a sensitivity advantage of breast MRI is this population [7]. Breast cancers occurring in the Li-Fraumeni syndrome (germline mutation of p53 on chromosome 17) affect women in their twenties and thirties, with 50% risk of breast cancer at 35 years, mostly with a family history of childhood cancer, sarcomas, brain tumors leukemia and adrenal cortex cancer. Another genetic predisposition is Cowden’s syndrome caused by PTEN mutation on chromosome 10 with association of multiple hamartomas, thyroid and breast cancer at a young age [4].

In very young women, breast cancers when diagnosed tend to report a longer history and are also larger than in older women. Physical examination of a lump in this population may be often difficult with dense or nodular breast tissue, complicated by cyclic menstrual changes. The clinical suspicion of malignancy is low as fibroadenomas are the most frequent palpable masses at this age. Mammography is less sensitive and specific in this population, mostly explained by the density of the mammary gland. Ultrasound is more likely to show an abnormality than mammography in this young group and cytology is needed for all focal lesions at this young age, if possible with ultrasound guidance. Presence of palpable mass and coincident imaging abnormality (even seemingly benign) in a young woman requires experienced further investigation. Fine needle and core biopsies are the investigations of choice and largely ensure a quick and accurate differentiation from the much more common benign fibroadenomas seen in women of this age group [9]. MRI might be useful but cannot be recommended as a routine examination [10, 11].

As there is no breast screening program in young women, most women detect their own lump. Ruddy et al. [12] described a self-detection rate of 80% in 585 patients <40 years of age diagnosed between 2006 and 2012 in 12 different sites across the USA. However, 17% of patients report self-delay in seeking medical attention of >90 days, mainly the less financially comfortable women. This suggests that, in this population, co-pays and hidden costs of seeking medical care such as child care expenses and lost wages may be obstacles to timely diagnosis and treatment particularly for such young women. Moreover, 12% of patients in this study report care delay >90 days between first clinical visit and diagnosis, reflecting the possibility of inadequate awareness of the disease or low suspicion for malignancy in professionals, as often described in clinical stories of AYAs with other cancers.

The incidence of breast cancer with distant involvement, associated with a poorer prognosis, has increased in recent years for women aged 25-39 years [13]. Breast cancer in AYAs is in its vast majority invasive cancer and exhibits a worse prognosis and has a more aggressive phenotype than in older patients. Cancers are larger in size, of higher grade, with a higher proportion of triple negative phenotype which carries a poorer prognosis, have a lower estrogen expression and a lower incidence of luminal A (less aggressive) tumors [14-18]. Age of onset in an independent prognostic risk factor; however, whether that is because a unique biology within subtypes or the result of higher frequency of more aggressive subtypes in the younger patients has been the subject of a debate thus far unresolved. The biological characteristics of AYA breast cancer are well reviewed in Tichy et al. [19] and Tricoli et al. [20]. Gene expression profiling studies to identify specific genes and molecular profiles are ongoing but without any clinical conclusion. A growing interest has emerged in the role of apparent age-related differences in the tumor-associated stroma [21]. Carefully controlled analyses of gene signatures in AYA tumors and stroma relative to the same subtypes in older patients are needed to determine if a specific pattern is linked to AYA breast cancer, with the backbone question of identifying molecular targets.

Therapeutic principles are similar between AYAs and relatively older women. However, some specific issues can usefully be underlined. Breast conservation is desirable in young women but only if it would also be indicated in an older woman. Low age is a factor for local re...