We searched Medline (through PubMed), and the Cochrane Central Library of Controlled Trials from January, 1966, to August, 2011, using the search terms “childhood”, “adolescent”, “neoplasm”, “Hodgkin”, “survivor”, “breast”, “radiation”, “alkylating”, “mammogram”, “magnetic resonance imaging”, and “clinical breast exam” (detailed search strategies are provided in the appendix [p 1]). Additionally, references supporting the existing recommendations were critiqued, and experts in the field
ReviewRecommendations for breast cancer surveillance for female survivors of childhood, adolescent, and young adult cancer given chest radiation: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group
Introduction
Advances in the treatment of childhood, adolescent, and young adult (CAYA) cancer over the past decades have greatly improved long-term survival, which now exceeds 80% for some cancer types.1, 2, 3 As a result, survivors of CAYA cancer are a growing group, and many have a high risk of premature morbidity and mortality due to previous cancer treatment.4, 5 Of particular concern is the substantially elevated risk for breast cancer among female survivors who were given radiation to fields in or encompassing the chest area, thereby including breast tissue—ie, thorax, whole lung, mediastinal, axilla, mini-mantle, subtotal lymphoid, high abdominal, and total body irradiation. Among this group, the cumulative incidence of breast cancer by age 40–45 years ranges from 13% to 20%, with standardised incidence ratios ranging from 13·3 to 55·5 per 10 000 person-years and absolute excess risk ranging from 18·6 to 79·0 per 10 000 person-years.6 The incidence of breast cancer after high-dose chest radiation in female survivors of CAYA cancer is similar to that in BRCA mutation carriers, in whom, by age 40 years, the cumulative incidence ranges from 10% to 19%.7, 8, 9, 10 In the general population, the cumulative incidence of breast cancer in women by age 45 years is only 1% to 2%.6, 11, 12 Because of the high breast cancer risk in female survivors of CAYA cancer, these individuals might benefit from tailored long-term breast cancer surveillance.
Clinical practice guidelines are needed to ensure that CAYA cancer survivors receive optimum care.13, 14, 15, 16 Survivors and health-care providers need guidance to be aware of and proactive about cancer-related and treatment-related health risks. To promote early detection and intervention for complications that might arise as a result of treatment for paediatric malignancies, clinical practice guidelines for long-term follow-up of CAYA cancer survivors have been developed by groups in North America and Europe.17, 18, 19, 20, 21 These guidelines differ regarding the definition of patient risk groups, and surveillance methods and frequencies. This raises uncertainty about which guidelines to follow, potentially hindering implementation, provision of, and adherence to clinically effective care. Recognising the need for collaboration, an international endeavour was initiated to harmonise guidelines for CAYA cancer survivors.22 The first aim of the International Late Effects of Childhood Cancer Guideline Harmonization Group was to harmonise recommendations for breast cancer surveillance for female survivors of CAYA cancer given chest radiation before age 30 years.
Section snippets
Concordance assessment and literature search
A detailed description of the international guideline harmonisation methods is provided elsewhere.22 These breast cancer surveillance recommendations were prepared by a core group consisting of eleven representatives from the North American Children's Oncology Group (COG),17 the Dutch Childhood Oncology Group (DCOG),18 the Scottish Intercollegiate Guidelines Network (SIGN),19 and the UK Children's Cancer and Leukaemia Group (UKCCLG).20 The recommendations were discussed in a working group of 31
Levels of evidence and strength of recommendations
As agreed by the International Guideline Harmonization Group, levels of evidence and strength of recommendations were determined using an adapted version of the Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria, and by applying the American Heart Association's classification of recommendations and level of evidence criteria.23, 24 The working group discussed the evidence and formulated recommendations for breast cancer surveillance in CAYA cancer survivors in
Guideline concordance and discordance
Table 1 shows concordance and discordance among breast cancer surveillance recommendations by COG,17 DCOG,18 and UKCCLG.20 There was concordance across guidelines for the following statements: female survivors of CAYA cancer who were given chest radiation have an increased risk for breast cancer; surveillance should be initiated at age 25 years or 8 years after radiation, whichever occurs last; surveillance should be done annually; and clinical breast examination, mammography, and breast MRI
Who needs breast cancer surveillance?
Women given therapeutic radiation to fields that include breast tissue are at increased risk of breast cancer at a younger age than the general population. The risk is especially high for women given high-dose chest radiation (≥20 Gy).6 However, for moderate-dose (10–19 Gy) and low-dose (1–9 Gy) chest radiation, the magnitude of breast cancer risk is unclear. There is evidence for a linear dose-response relationship, but precise risk estimates for exposures of 1–9 Gy and 10–19 Gy have not been
At what age should breast cancer surveillance be initiated?
Studies have shown that breast cancer risk in female survivors of CAYA cancer is increased as early as 8 years after radiation, and that the cumulative breast cancer incidence increases from age 25 years onwards.6, 32, 34, 35, 36, 37 We recommend beginning breast cancer surveillance at age 25 years or 8 years after radiation, whichever occurs last. For women who were given high-dose chest radiation (≥20 Gy), the benefits of starting surveillance at age 25 years outweigh the harms. For women who
At what frequency should breast cancer surveillance be done?
There is evidence that breast cancer risk in female survivors of CAYA cancer who were given chest radiation increases with length of follow-up;6, 32, 34, 35, 36, 37 however, an appropriate surveillance interval is difficult to define. It is essential to detect breast cancer early, since women diagnosed in an early stage have a higher likelihood for a favourable outcome and a survival benefit.38, 58, 59, 60, 61, 62 For women with node-positive breast cancer, the therapy given for the initial
At what age should breast cancer surveillance be stopped?
With follow-up of women to age 50 years, it does not seem that the increased breast cancer risk in CAYA cancer survivors who were given chest radiation diminishes with age. Although larger studies with extended follow-up are needed to substantiate this observation, the biological mechanisms of radiation-induced breast tissue apoptosis and carcinogenesis suggest that the cumulative incidence of breast cancer will continue to increase with age, and that the excess risk will remain substantially
Evidence in CAYA cancer survivors
So far, there is little evidence describing the diagnostic value of different breast cancer surveillance methods in female survivors of CAYA cancer who were given chest radiation. Three prospective surveillance studies assessed screening mammography in 320 adult women (median age ranged from 35 to 41 years) who survived childhood or young adult Hodgkin's lymphoma.39, 40, 41 The strengths and limitations of each of these studies were discussed by Henderson and colleagues.6 Increased breast
Conclusion
In this report, we presented international, harmonised, breast cancer surveillance recommendations for female survivors of CAYA cancer who were given chest radiation before age 30 years. Based on the evidence and consensus among the group, we formulated recommendations that are intended to be consistent and scientifically rigorous, to positively affect health outcomes, and to facilitate consistent follow-up care globally for female survivors of CAYA cancer given chest radiation.
There is
Search strategy and selection criteria
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