Jun 02, 2011
Smita Bhatia, MD, MPH
City of Hope Comprehensive Cancer Center
Women exposed to chest radiation during childhood or adolescence for an unrelated cancer are at an increased risk of breast cancer. Overall, childhood cancer survivors are at a 13- to 55-fold increased risk compared with an age- and sex-matched general population. The absolute excess risk ranges from 18.6-79 per 10,000 person-years, and the cumulative incidence from 12%-26% after 25-30 years from radiation exposure.1-4 The risk of breast cancer has been found to increase as early as eight years from radiation exposure and continues to increase with time from exposure.1 The cumulative incidence of breast cancer by age 40-45 ranges from 13%-20%.1,2,4 The median age at diagnosis of breast cancer is 36, at least 25 years earlier than that observed in the general population.
The risk is strikingly similar to that observed for women with a BRCAgene mutation, where, by age 40, the cumulative incidence of breast cancer ranges from 10%-19%,5 and is substantially higher than the risk for womenin the general population (1% at acomparable age).6 Because of the similarity in risk of breast cancer between women receiving chest radiation and those with a BRCA mutation, it is logical to assume that similar recommendations, in terms of age at initiation, frequency of screening, and screening modalities should apply to the former group. Although currently available evidence is insufficient to demonstrate a survival benefit from the initiation of breast cancer surveillance in women treated with chest radiation for childhood cancer, interventions to promote detection of small and early-stage tumors may improve prognosis,particularly for those who may have more limited treatment options because of prior exposure to radiation or anthracyclines.7
In the feature that follows, clinicians from the United Kingdom (U.K.) and United States (U.S.) briefly discuss how breast cancer surveillance recommendations for this high-risk population were developed and implemented within their countries, with special reference to common and unique access issues and barriers within the respective health care systems. Theperspectives presented underscore the need for more research, on both sides of the pond, to expand the evidence base, better understand the benefits and harms of the various breast cancer surveillance options, and to test interventions aimed at overcoming individual-, provider-, and system-level barriers.
Dr. Bhatia is the first holder of Ruth Ziegler Chair in Population Sciences. In addition, she holds several positions at City of Hope National Medical Center, including Chair, Department of Population Sciences, Associate Director for Population Research at the Comprehensive Cancer Center, and Director of the Center for Cancer Survivorship. She is a member of the ASCO Cancer Survivorship Committee and has served on the Cancer Prevention Committee and the Journal of Clinical Oncology Editorial Board. She is the Associate Chair of the Children’s Oncology Group.
Developing and Implementing Breast Cancer Surveillance Recommendations in the U.K.
Gill Levitt, BSc, MRCP, MRCPCH
Great Ormond Street Hospital for Children
Roderick Skinner, MB, ChB
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
In 2003, the U.K. Department of Health (DH) and the National Health Service (NHS) Breast Cancer Screening Programme released a recommendation for female Hodgkin lymphoma survivors treated with chest radiation prior to age 36.8 Initiation of screening begins at age 25 or eight years after radiation, whichever occurs last. Annual MRI is recommended for those age 25-29. At age 30, a baseline two-view mammogram is assessed. If the mammogram shows predominantly fatty tissue, then the woman has annual mammography until age 49.
For women with dense breast tissue at baseline mammography, an annual breast MRI is combined with mammography. If the breast tissue becomes predominantly fatty prior to age 50, screening continues with annual mammography alone. Once a survivor is 51, the screening recommendation follows the average risk (general population) guideline consisting of mammography every three years.
Concurrent with the release of the above recommendations, the DH set up a retrospective national notification and screening program for the approximately 5,000 women who were treated from 1962 onwards for Hodgkin lymphoma with supra-diaphragmatic radiation prior to age 36.8 The DH, working with the cancer network lead clinicians and regional cancer registries, identified eligible women and notified them by mail of their risk of breast cancer and invited them back to the lymphoma clinic for a single visit. At the clinic visit, the above recommendation for breast cancer screening was discussed and breast cancer screening tests ordered if desired. The new surveillance recommendations were made public by the press.
Access and participation
Through the U.K. NHS, there is universal access to the recommended breast cancer screening, according to the protocol described above. However, this access does not include other women treated with chest radiation for other cancers (e.g., non-Hodgkin lymphoma, Wilms tumor, sarcoma) during their pediatric or young-adult years. U.K. investigators have undertaken preliminary investigations to evaluate uptake and potential facilitators and barriers of breast cancer surveillance recommendations following the 2003 U.K. DH notification. Howell et al reported that only 58% (243/417) of eligible women in the Greater Manchester and Cheshire Cancer Network, the largest cancer network in England, responded to the notification and attended the lymphoma clinic visit.9 Among eligible women in the Weston Park Hospital, Sheffield area, 76% (77/101) attended a lymphoma clinic visit.10 Fifty-six of these women were interviewed before risk counseling and again following screening and results (50 patients).11 Absolom et al found that 64% learned more about late effects, 76% were reassured about their health, and that women were generally keen to take advantage of screening and experienced relatively little distress. To date, there are no published data on the national uptake of breast cancer surveillance from this notification exercise. Since 2003, there has not been another national effort to notify patients or general practitioners.
New initiativesTwo current initiatives seek to improve the care of children and young people treated for cancer in England. The National Institute for Health and Clinical Excellence (NICE) has published Improving Outcomes Guidance with quality standards against which cancer centers are now judged by regular peer review.12 The second is the DH-funded National Cancer Survivorship Initiative, which aims to improve the lives of those living with and beyond cancer, including appropriate care for cancer survivors as well as surveillance for later consequences of cancer and its treatment. This initiative has recommended that all patients receive a summary of the treatment they received and a care plan to outline the risk for specific late adverse effects of treatment and planned surveillance to facilitate earlier detection. It is anticipated that prospective provision of such information soon after completion of treatment will improve follow-up and surveillance uptake rates. Although Hodgkin lymphoma survivors are recognized to be at particularly high risk of breast cancer following radiotherapy and have a national surveillanceprogram in place, other patient groups who received irradiation involving breast tissue are not included in the program. While less evidence is available than for Hodgkin lymphoma survivors, it appears logical to suggest similar surveillance for these survivors.9
Dr. Levitt is a Consultant in Pediatric Oncology at Great Ormond Street Hospital for Children NHS Trust. Her research and patient care interests include the treatment and late effects of treatment for childhood malignant disease in particular solid tumours.
Dr. Skinner is a pediatric oncologist at Royal Victoria Infirmary. His professional interests include the late side-effects of treatment for cancer and leukemia in children, as well as bone marrow transplantation and aplastic anemia in children.
Developing and Implementing Breast Cancer Surveillance Recommendations in the U.S.
Kevin C. Oeffinger, MD
Memorial Sloan-Kettering Cancer Center
In 2002, the Institute of Medicine charged the Children’s Oncology Group (COG) with development of comprehensive clinical practice guidelines for long-term follow-up care of childhood cancer survivors.13,14 Based upon the available evidence and an assessment of the potential benefits and harms of different breast cancer surveillance options, COG recommended in 2003 that women treated for a pediatric cancer with moderate- to high-dose chest radiation (> 20 Gy) initiate annual screening mammography at age 25 or eight years after the radiation, whichever occurs last. In 2008, the recommendations were revised to alsoinclude an annual breast MRI.15 These recommendations have been adopted as the standard of care in the U.S. and are consistent with those of the American Cancer Society.16
Because a national or regional method to notify women of their risk of breast cancer does not exist in the U.S., dissemination efforts have largely been undertaken through posting of the COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers on a publicly available website.17 COG investigators have also contributed to efforts to increase clinician awareness of the risk of breast cancer in women treated with chest radiation through multiple avenues, including primary care-based journals, continuing medical education monographs, and through national and regional meetings.
Access and participation
There is no national health plan in the U.S.; universal access to breast cancer surveillance methods is not available. Instead, the cost of surveillance is either covered through private health insurance plans, public assistance programs (e.g., Medicaid, Medicare), or paid by the individual. Notably, 22.8% of U.S. women age 25-34 and 19.8% of U.S. women age 35-44 are currently without any form of health insurance.18 Many others are underinsured. Most private health insurance plans include coverage of breast MRI in this population of women; however, some insurers and Medicaid require a pre-authorization letter stating that the woman has a lifetime risk of breast cancer of 20% or more. For women without health insurance or with inadequate insurance, the cost of breast MRI generally prohibits the use of this mode of screening. Uptake of COG breast cancer surveillance recommendations is also challenged by the fact that adult survivors of pediatric cancer in the U.S. are not followed at a cancer center, but rather by a primary care physician or obstetrician/gynecologist, most of whom are unaware of the substantially heightened risk of breast cancer among these women.19-21
In 2005-2006, Childhood Cancer Survivor Study (CCSS) investigators interviewed women in the U.S. and Canada, age 25-50 years, who had survived pediatric cancer and whose treatment included chest radiation.22 Of those younger than 40 years, 47% had never had a mammogram or other breast imaging study. The most common barriers among younger women were their lack of awareness of the risk or the lack of recommendation for screening from their primary physician. Only 53% of women age 40-50 were being regularly screened. Less than 3% reported ever having a breast MRI.
These data have motivated increased efforts to develop effective interventions to educate providers and survivors about the need for breast cancer surveillance in this high-risk group. In a prospective feasibility study conducted among a random sample of 72 Hodgkin lymphoma survivors in the CCSS who were at increased risk for breast cancer and had not had a screening mammogram within the prior two years, distribution of a one-page survivorship care plan with breast cancer surveillance recommendations prompted 41% to complete a mammogram.23 These data informed an ongoing randomized clinical trial through the CCSS that is testing the effectiveness of a mail- and telephone-based intervention aimed at communicating with women about risk and the COG recommendation.
In 2010, the Patient Protection and Affordable Care Act (PPACA) was signed into U.S. law. PPACA willprohibit denial of coverage based upon preexisting conditions, such as a history of childhood cancer. Thus,the PPACA may provide coverage for breast cancer surveillance for many cancer survivors who are currently unable to access the recommended screening tests. In addition, since many of these women have chronic diseases related to their cancer therapy,24the PPACA may influence the type of health care and preventive services available for these women.25 The effect of PPACA is yet to be determined, but offers the potential to improve access to breast cancer surveillance among women in this high-risk group.
Dr. Oeffinger is a primary care physician and Director of the Adult Long-Term Follow-Up Program at Memorial Sloan-Kettering Cancer Center. He is a member of the ASCO Cancer Survivorship Committee and has served on the Journal of Clinical Oncology Editorial Board. He also serves on the Late Effects and Outcomes Steering Committee of the Children’s Oncology Group and the Survivorship Research Task Force for the American Association for Cancer Research.
- Bhatia S, Yasui Y, Robison LL, et al. J Clin Oncol. 2003;21:4386-94.
- Kenney LB, Yasui Y, Inskip PD, et al. Ann Intern Med. 2004;141:590-7.
- Ng AK, Bernardo MV, Weller E, et al. Blood. 2002;100:1989-96.
- Taylor AJ, Winter DL, Stiller CA, et al. Int J Cancer. 2007;120:384-91.
- Easton DF, Ford D, Bishop DT. Am J Hum Genet. 1995;56:265-71.
- Fay MP, Pfeiffer R, Cronin KA, et al. Stat Med. 2003;22:1837-48.
- Tabár L, Duffy SW, Vitak B, et al. Cancer. 1999;86:449-62.
- United Kingdom Department of Health; Cancer Policy Team. Increased risk of breast cancer after radiotherapy for Hodgkin’s Disease: Patient Notification Exercise. London: Department of Health, 2003. NHS Breast Screening Programme. Accessible at http://www.cancerscreening.nhs.uk/breastscreen/.
- Howell SJ, Searle C, Goode V, et al. Br J Cancer. 2009;101:582-8.
- Greenfield DM, Wright J, Brown JE, et al. Br J Cancer. 2006;94:469-72.
- Absolom K, Greenfield D, Ross R, et al. Breast. 2007;16:590-6.
- Improving Outcomes Guidance National Institute for Health and Clinical Excellence (NICE) Accessible at http://guidance.nice.org.uk/CSGCYP.
- Hewitt M, Weiner S, Simone JV, eds. Childhood Cancer Survivorship: Improving Care and Quality of Life. Washington, DC: National Academies Press; 2003.
- Landier W, Bhatia S, Eshelman DA, et al. J Clin Oncol. 2004;22:4979-90.
- Henderson TO, Amsterdam A, Bhatia S, et al. Ann Intern Med. 2010;152:444-55; W144-54.
- Saslow D, Boetes C, Burke W, et al. CA Cancer J Clin. 2007;57:75-89.
- Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer. 2008; Version 3.0. Accessible at http://www.survivorshipguidelines.org.
- Martinez ME, Cohen RA. Health insurance coverage: Early release of estimates from the National Health Interview Survey, January–June 2010. National Center for Health Statistics. December 2010. Accessible at http://www.cdc.gov/nchs/nhis.htm.
- Nathan PC, Greenberg ML, Ness KK, et al. J Clin Oncol. 2008;26:4401-9.
- Oeffinger KC, Mertens AC, Hudson MM, et al. Ann Fam Med. 2004;2:61-70.
- Oeffinger KC, Robison LL. JAMA. 2007;297:2762-4.
- Oeffinger KC, Ford JS, Moskowitz CS, et al. JAMA. 2009;301:404-14.
- Oeffinger KC, Hudson MM, Mertens AC, et al. Pediatr Blood Cancer. 2011;56:818-24.
- Oeffinger KC, Mertens AC, Sklar CA, et al. N Engl J Med. 2006;355:1572-82.
- Laiteerapong N, Huang ES. JAMA. 2010;304:899-900.
Current Controversies in Oncology is a forum for the exchange of views on topical issues in the field of oncology. The views and opinions expressed therein are those of the authors alone. They do not necessarily reflect the views or positions of the Editor orof the American Society of Clinical Oncology.