Abstract
Background
The aim of the current study was to investigate the pattern of cancer screening behavior in adult retinoblastoma survivors, who are at high risk of developing second cancers.
Methods
Self-reported cancer screening practices were investigated in a cohort of retinoblastoma survivors to evaluate whether they were receiving adequate screening for specific cancers and compare these rates with those of other adult survivors of childhood cancer and the general population. The prevalence of breast self-examination, clinical breast examination, mammography, Papanicolaou (Pap) test, testicular self-examination, and magnetic resonance imaging (MRI) or computed tomography (CT) scanning was determined from computer-aided telephone interviews with 836 retinoblastoma survivors aged >18 years.
Results
Among female survivors, 87% had a Pap test within the past 2 years, and 76% of females age >40 years reported having a mammogram within the past 2 years; 17.4% of male survivors had performed monthly testicular self-examinations. A significantly higher proportion of hereditary compared with nonhereditary survivors reported having undergone an MRI or CT scan in the past 5 years. Higher education, greater contact with the medical care system, and having a second cancer were found to be associated positively with most screening practices. Cancer screening practices reported by retinoblastoma survivors were similar to national screening rates for breast, cervical, and testicular cancer.
Conclusions
To the authors' knowledge, the current study provides the first report of cancer screening practices of retinoblastoma survivors. Survivors of hereditary retinoblastoma should be encouraged to maintain, if not increase, their current screening practices to ensure early detection of second cancers in this high-risk population.
Retinoblastoma (Rb), a rare childhood cancer of the eye, occurs in a hereditary form related to germline mutations in the RB1 tumor suppressor gene, and a nonhereditary form related to somatic mutations or inactivation in the same gene. Because of a reported survival rate of 97% at 5 years,1 the population of long-term Rb survivors is growing, and many individuals are now adults. Survivors of hereditary Rb have a significantly elevated risk of developing second cancers, whereas survivors with the nonhereditary form are not prone to developing a secondary cancer.2–5 The most common second cancers in hereditary patients are soft-tissue sarcomas, osteosarcomas, nasal cavity cancers, and cutaneous melanoma.2, 4, 5 Radiologic imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) scans are sensitive tools for detecting sarcomas.
In addition to these more frequent second cancers in hereditary patients, we noted a statistically significant increase in the risk of breast cancer in hereditary (observed, 10 cases; standardized incidence ratio [SIR] of 3.96 [95% confidence interval (95% CI), 1.9–7.3]) and nonhereditary Rb (observed, 7 cases; SIR of 2.8 [95% CI, 1.1–5.9]) survivors.4 This increased risk for breast cancer was noted in patients treated with radiotherapy for Rb, and could be related to the small scatter radiation dose (0.40 Gray [Gy]) to the breasts, which has been associated with an increased breast cancer risk in studies of infants who underwent radiotherapy for enlarged thymus glands and hemangiomas.6, 7 In addition, somatic mutations in the RB1 gene have been detected in breast cancers in non-Rb patients.8–10 Alternatively, the increased risk for breast cancer after Rb could partially be because of more intense breast cancer screening of these patients, because hereditary Rb patients who received radiotherapy are known to be at an increased risk of developing a second cancer.
To our knowledge to date, few studies have been published that describe the cancer screening practices of survivors of various childhood and adolescent cancers11–13 and, to our knowledge, none have been published on survivors of retinoblastoma. With the number of childhood cancer survivors increasing and the recognition of treatment related to second cancers gaining more prominence, researchers have identified the need to develop and implement evidence-based recommendations for clinical follow-up, including cancer screening, based on clinical and epidemiologic studies.14, 15 In addition, it is important for all patients to receive adequate screening for cancers that are prevalent in the general population, while focusing on those cancers for which retinoblastoma survivors are at increased risk.
MATERIALS AND METHODS
For this retrospective cohort study, 1601 1-year survivors of Rb diagnosed between 1914 and 1984 who were treated at 2 medical centers in New York and Boston were identified.4 Data regarding medical history, family history of Rb, treatment for Rb, reports of additional cancers, and causes of death were collected from medical records, radiotherapy records, periodic searches of the National Death Index, and 3 subsequent telephone interviews with Rb survivors or their parents in 1987, 1993, and 2000.4, 16, 17 The Institutional Review Board of the National Institutes of Health approved this study.
When we conducted the most recent telephone interview with survivors in 2000, 1169 (73%) were still alive, 385 (24%) had died, and 47 (2.9%) were lost to follow-up.18 In all, 875 survivors (75%) responded to a computer-aided telephone interview (CATI) survey. Nonresponders did not differ significantly from responders by year of birth, age at survey, sex, hereditary status, age at Rb diagnosis, or treatment for Rb. Our current analysis excluded 39 survivors who were aged <18 years at the time of the survey because they would have been unlikely to have been screened for cancer. The current study included 836 respondents who were aged ≥18 years.
Cancer Screening Outcome Measures
The survey was administered to study subjects by trained telephone interviewers. Female Rb survivors were asked about their frequency of monthly breast self-examination, the last time they had a breast examination by a physician or a healthcare professional, a mammogram, and a Papanicolaou (Pap) test. Male Rb survivors were asked about their frequency of testicular self-examination. We also asked all survivors about the frequency and reason for MRI or CT scan within the past 5 years. We categorized the reasons for screening into 5 categories: 1) trauma; 2) surveillance primarily related to detection of a second cancer; 3) staging of an existing cancer; 4) evaluation of new symptoms, mainly migraines, unexplained pain; and 5) other, including sinus and varied orthopedic problems.
Statistical Methods
We used a chi-square for 2 independent samples to test for differences in selected characteristics and the prevalence of cancer screening practices between hereditary and nonhereditary survivors. We used unconditional logistic regression to explore factors associated with cancer screening prevalence in the cohort. These factors included age at interview, level of education (less than high school graduate, high school/some college, or college graduate), race (white, nonwhite), radiotherapy for Rb, hereditary Rb status, ever hospitalized within the past 5 years for any reason besides childbirth, ever taken birth control pills, ever taken hormone replacement therapy for menopausal symptoms, and ever diagnosed with a second cancer. The maximum likelihood estimates and 95% Wald-type confidence interval were computed.
We focused most of the analyses on mammography in women aged ≥40 years because this is the recommended age at which to begin routine mammography,19 and national rates are not available for women aged <40 years.20 However, when we compared the rates of mammography in Rb survivors with those in other childhood cancer survivors, we included all women aged ≥30 years to be comparable to the rates reported for childhood cancer survivors.13 Pap screening rates for the U.S. are available for all women aged ≥18 years. We were not able to age-adjust these comparisons because these data were not available; however, we did restrict the comparisons to similar age ranges. We used U.S. screening rates from 2000, the same year as the Rb survey.
RESULTS
Baseline Characteristics
Of the 836 respondents to the 2000 CATI survey, 441 (53%) were hereditary survivors and 395 (47%) were nonhereditary survivors of Rb (Table 1). Respondents ranged in age from 18 to 73 years (mean age, 35 years). The majority of subjects in this cohort were white (91.2%) and college graduates (46.5%). Hereditary survivors were more likely than nonhereditary survivors to have been hospitalized within the past 5 years (32.9% vs 21.0%; P ≤ .001) and to report a second cancer (10% vs 1.8%; P ≤ .001).
TABLE 1.
Selected Characteristics of 836 1-Year Retinoblastoma Survivors Who Responded to a Telephone Interview
| Characteristic | Hereditary (n = 441) no. (%) |
Nonhereditary (n = 395) no. (%) |
P |
|---|---|---|---|
| Age at interview, y* | |||
| <25 | 71 (16.1) | 72 (18.2) | |
| 25–29 | 73 (16.6) | 68 (17.2) | |
| 30–34 | 92 (20.9) | 51 (12.9) | |
| 35–39 | 90 (20.4) | 80 (20.3) | |
| 40+ | 115 (26.1) | 124 (31.4) | .035 |
| Sex | |||
| Male | 241 (54.6) | 198 (50.4) | |
| Female | 200 (45.4) | 196 (49.6) | .217 |
| Race† | |||
| White | 402 (91.6) | 357 (90.8) | |
| Nonwhite | 37 (8.4) | 36 (9.2) | .709 |
| Education‡ | |||
| <High school graduate | 34 (7.9) | 22 (5.7) | |
| High school/some college | 202 (47.0) | 177 (46.1) | |
| College graduate | 194 (45.1) | 185 (48.2) | .398 |
| Hospitalized within the past 5 y§ | |||
| No | 294 (67.1) | 309 (79.0) | |
| Yes | 144 (32.9) | 82 (21.0) | <.001 |
| History of second cancer | |||
| No | 396 (89.8) | 388 (98.23) | |
| Yes | 45 (10.2) | 7 (1.8) | <.001 |
Excludes all retinoblastoma survivors aged <18 years.
Data unknown for 4 subjects.
Data unknown for 22 subjects.
Hospitalized for any reason except childbirth.
Frequency of Cancer Screening
Overall, female survivors did not differ significantly in their frequency of screening examinations by hereditary status (Table 2). A very high proportion of both hereditary (85.8%) and nonhereditary (88.4%) survivors reported Pap screening within the past 2 years. Among women aged ≥40 years, 10 women (8%) had never had a mammogram. Fewer hereditary survivors compared with nonhereditary survivors aged ≥40 years reported undergoing mammography within the past 2 years (71.2% vs 79.1%, respectively).
TABLE 2.
Frequency of Self-Reported Cancer Screening in 1-Year Retinoblastoma Survivors by Hereditary Status
| Type of cancer screening examination |
Hereditary no. (%) |
Nonhereditary no. (%) |
P |
|---|---|---|---|
| Females only | |||
| Breast self-examimation | |||
| Rarely/never | 51 (26.0) | 53 (28.2) | |
| Occasionally | 67 (34.2) | 69 (36.7) | |
| Regularly* | 78 (39.8) | 66 (35.1) | |
| Total† | 196 (100.0) | 188 (100.0) | .637 |
| Clinical breast examination | |||
| Never | 9 (4.6) | 7 (3.7) | |
| <1 y ago | 133 (67.5) | 136 (72.0) | |
| 1–2 y ago | 44 (22.3) | 35 (18.5) | |
| ≥3 y ago | 11 (5.6) | 11 (5.8) | |
| Total | 197 (100.0) | 189 (100.0) | .767 |
| Pap test | |||
| Never | 11 (5.6) | 12 (6.3) | |
| <1 y ago | 116 (58.9) | 133 (70.4) | |
| 1–2 y ago | 53 (26.9) | 34 (18.0) | |
| ≥3 y ago | 17 (8.6) | 10 (5.3) | |
| Total | 197 (100.0) | 189 (100.0) | .072 |
| Mammography‡ | |||
| Never | 3 (5.8) | 7 (10.4) | |
| <1 y ago | 16 (30.8) | 22 (32.8) | |
| 1–2 y ago | 21 (40.4) | 31 (46.3) | |
| ≥3 y ago | 12 (23.1) | 7 (10.4) | |
| Total | 52 (100.0) | 67 (100.0) | .266 |
| Males only | |||
| Testicular self-examination | |||
| Rarely/never | 124 (52.8) | 127 (66.5) | |
| Occasionally | 59 (25.1) | 42 (22.0) | |
| Regularly* | 52 (22.1) | 22 (11.5) | |
| Total | 235 (100.0) | 191 (100.0) | .005 |
Pap indicates Papanicolaou.
Once a month.
Total differs due to missing information.
Includes women aged ≥40 y only.
Male survivors differed significantly in their frequency of testicular self-examination by hereditary status (P < .005). Among hereditary survivors, twice as many had performed a testicular examination regularly compared with nonhereditary survivors (22.1% vs 11.5%).
Among hereditary Rb survivors, we did not note any statistically significant difference in the proportion of Rb survivors affected by bilateral or unilateral eye disease receiving cancer screening examinations.
Eleven of 16 Rb female survivors in the cohort who were diagnosed with breast cancer had responded to the latest telephone survey. All 11 reported having had a mammogram, but only 1 reported that a routine mammogram had detected her cancer. These 11 women ranged in age from 34 to 59 years at the time of breast cancer diagnosis. Information regarding breast tumor size was available for 9 women: 2 had tumors measuring <1.2 cm, 3 had tumors measuring 1 to 4 cm, and 4 had tumors measuring ≥5 cm at the time of diagnosis.
Multivariate Risk Factors Related to Cancer Screening
A higher level of education was found most consistently to be related to all of the screening practices that we evaluated (Table 3). Women who had used birth control pills were 2 times more likely to have had a clinical breast examination within the past year and 7 times more likely to report a Pap test within 3 years. The use of hormone replacement therapy was found to be strongly but nonsignificantly associated with having undergone a mammogram within the past 2 years. Survivors who had a second cancer diagnosed were 3 times more likely than survivors without a second cancer to report a breast self-examination within the last year or to perform regular testicular self-examinations.
TABLE 3.
Multivariate Risk Factors Predicting Cancer Screening Practices in 1-Year Retinoblastoma Survivors
| Female | Male | ||||
|---|---|---|---|---|---|
| Breast self-examinations* | Clinical breast examinations† | Mammogram‡ | Pap test§ | TSE‖ | |
| Age at interview, y | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) |
| 18–24 | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | |
| 25–29 | 1.75 (0.76–4.04) | 0.72 (0.30–1.72) | 0.89 (0.30–2.67) | 1.20 (0.49–2.91) | |
| 30–34 | 1.49 (0.64–3.44) | 0.85 (0.36–2.01) | 2.96 (0.80–10.89) | 0.66 (0.26–1.67) | |
| 35–39 | 1.44 (0.66–3.12) | 0.77 (0.35–1.66) | 3.10 (1.07–8.96) | 1.40 (0.60–3.31) | |
| ≥40 | 2.54 (1.16–5.57) | 1.50 (0.66–3.37) | 1.00 | 2.97 (1.04–8.49) | 0.60 (0.29–1.49) |
| ≥50 | NA | NA | 0.91 (0.24–3.36) | NA | NA |
| Education | |||||
| <High school graduate | 0.71 (0.23–2.24) | 0.82 (0.27–2.52) | 0.05 (0.004–0.70) | 0.45 (0.11–1.81) | 0.87 (0.33–2.31) |
| High school /some college | 0.91 (0.57–1.45) | 0.68 (0.41–1.12) | 0.83 (0.3–2.31) | 0.68 (0.32–1.43) | 0.51 (0.29–0.91) |
| College graduate | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| Race | |||||
| White | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| NonWhite | 1.75 (0.74–3.39) | 0.61 (0.27–1.39) | 0.78 (0.1–6.0) | 1.06 (0.32–3.49) | 0.76 (0.27–2.10) |
| Radiotherapy for Rb | |||||
| No | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| Yes | 1.57 (0.81–3.02) | 0.95 (0.47–1.89) | 0.69 (0.16–3.01) | 0.41 (0.14–1.13) | 1.10 (0.45–2.69) |
| Hereditary Rb status | |||||
| Nonhereditary | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| Hereditary | 0.84 (0.43–1.61) | 0.83 (0.42–1.66) | 0.47 (0.11–2.04) | 1.41 (0.51–3.86) | 1.95 (0.79–4.82) |
| Hospitalized within past 5 y | |||||
| No | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| Yes | 0.95 (0.58–1.56) | 0.81 (0.49–1.36) | 1.95 (0.65–5.38) | 1.16 (0.56–2.39) | 0.49 (0.25–0.99) |
| Ever taken birth control pills | |||||
| No | 1.00 (referent) | 1.00 (referent) | – | 1.00 (referent) | NA |
| Yes | 0.98 (0.59–1.63) | 2.80 (1.60–4.89) | – | 7.71 (2.77–21.44) | NA |
| Ever taken hormone replacement therapy | |||||
| No | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | NA |
| Yes | 0.86 (0.38–1.94) | 0.99 (0.41–2.41) | 6.60 (1.06–40.98) | 1.19 (0.31–4.54) | NA |
| Ever had a second cancer | |||||
| No | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) |
| Yes | 0.38(1.36–8.38) | 2.11 (0.73–6.15) | 2.03 (0.40–10.29) | 0.87 (0.25–3.02) | 3.46 (1.32–9.06) |
Pap indicates Papanicolaou; TSE, testicular self-examination; OR, odds ratio; 95% confidence interval; NA, not applicable; RB, retinoblastoma.
Breast self-examination performed regulary (once a month).
Clinical breast examination performed within last year.
For females aged ≥40 years, report of having a mammogram within past 2 years.
Papnicolaou testing within past 3 years.
Testicular self-examination performed regularly (once a month).
Although not statistically significant, survivors who received radiotherapy for Rb were more likely to perform breast self-examination or testicular self-examination, but less likely to have reported a clinical breast examination, mammogram, or Pap test. Hereditary Rb survivors were more likely to have had a Pap test or testicular self-examination, but less likely to have had a breast self-examination, clinical breast examination, or mammogram compared with nonhereditary patients.
Comparison With Other Childhood Cancer Survivors and the U.S. Population
Rb survivors reported a similar prevalence of mammography (58%) compared with other similarly aged childhood cancer survivors who had received chest or mantle irradiation (57%).13 A higher proportion of Rb survivors reported monthly breast self-examination compared with childhood cancer survivors who had received chest or mantle radiation therapy (40% vs 34%), whereas a clinical breast examination within the past year was reported by slightly fewer Rb survivors compared with childhood cancer survivors who had received chest or mantle radiotherapy (71% vs 73%). More Rb survivors aged >18 years had had a Pap test within the past 3 years compared with other childhood cancer survivors (87.0% vs 78.2%). Male Rb survivors reported the same level of testicular self-examination screening compared with other childhood cancer survivors (17.4% for both).
A similar percentage of Rb survivors aged ≥40 years reported receiving a mammogram within the past 2 years compared with the white, general U.S. population (76% vs 72%). The percentage of Rb survivors having a Pap test in the past 3 years was also similar compared with the U.S. population (87% vs 86%).
Frequency of MRI or CT Scanning
A significantly higher proportion of hereditary compared with nonhereditary survivors reported having undergone an MRI or CT scan within the past 5 years (39% vs 24%; P < .001) (Table 4). Hereditary survivors were 3 times more likely to report that their MRI or CT scan was for screening for a second cancer compared with nonhereditary survivors (26% vs 8%), and 13 of these 45 hereditary patients who reported an MRI or CT for this reason had a documented second cancer. These included 6 cancer diagnoses in the head area and 7 in the trunk or limbs. Nonhereditary survivors were twice as likely to be evaluated for trauma compared with hereditary survivors (28% vs 13%) and for new symptoms of migraines and other conditions (45% vs 39%).
TABLE 4.
Frequency of Self-Reported MRI or CT Scan Within the Past 5 Years in 1-Year Retinoblastoma Survivors by Hereditary Status
| MRI or CT scan | Hereditary no. (%) |
Nonhereditary no. (%) |
Chi-square P |
|---|---|---|---|
| No. of MRI or CT scans | |||
| None | 271 (61.5) | 300 (76.0) | |
| 1 | 80 (18.1) | 55 (13.9) | |
| 2–4 | 61 (13.8) | 30 (7.6) | |
| ≥5 | 29 (6.6) | 10 (2.5) | <.001 |
| Reason scan was performed | |||
| Trauma* | 22 (12.9) | 27 (28.4) | |
| Surveillance† | 45 (26.5) | 8 (8.4) | |
| Staging‡ | 11 (6.5) | 2 (2.1) | |
| Evaluation of new symptoms§ | 66 (38.8) | 43 (45.3) | |
| Other | 26 (15.3) | 15 (15.8) | <.001 |
MRI indicates magnetic resonance imaging; CT, computed tomography.
Orthopedic injuries.
Screening of asymptomatic second cancer after retinoblastoma.
Staging of cancer.
Evaluation of headaches, migraines, kidney stones, etc.
DISCUSSION
Although hereditary Rb survivors are at a much higher risk of developing a second cancer compared with nonhereditary survivors, current cancer screening behavior reported by this large cohort of adult Rb survivors indicates that female hereditary and nonhereditary survivors do not differ significantly with regard to their frequency of breast self-examinations, clinical breast examinations, mammography, and Pap tests, whereas male hereditary survivors were twice as likely as nonhereditary survivors to perform a regular testicular self-examination. A higher level of education and more contact with the medical system because of a second cancer, a hospitalization within the past 5 years, taking birth control pills, or taking hormone replacement therapy were found to be positively associated with screening practices. The use of an MRI or CT scan to screen Rb survivors for a second cancer was 3 times more common among hereditary compared with nonhereditary survivors, which is consistent with the higher risk of second cancers noted among hereditary survivors. Current screening practices of Rb survivors were similar to national screening levels for breast, cervical, and testicular cancer. Current screening practices of Rb survivors were somewhat higher than those of other childhood cancer survivors, except for testicular self-examination, which were similar.
It is not clear why female Rb survivors, who either received radiotherapy or had the hereditary form of Rb, were less likely to have a clinical breast examination or mammography. It is possible that this is attributable to differences in age related to hereditary status because approximately one-third of nonhereditary survivors were aged ≥40 years, compared with 26% of hereditary survivors. This lack of screening may point to a need for this higher-risk population to receive more breast cancer screening given their higher risk of breast cancer.
We observed that a higher level of education is associated with cancer screening practices in females, a finding that is consistent with data regarding other childhood cancer survivors13 and national screening data.20 The strong association between oral contraceptive use and ever having had a Pap test, as well as that between the use of hormone replacement therapy and clinical breast examination and mammography in women aged ≥40 years, support the notion that women with more frequent contact with the healthcare system receive more overall cancer screening procedures. This has also been noted for mammography in the general population.21
To our knowledge, the current study is the first report of the prevalence of MRI or CT scanning to screen for second cancers in adult Rb survivors. Neuroimaging with MRI has been recommended for screening of primitive neuroectodermal tumors in very young hereditary Rb survivors. However, a series of 226 Rb patients did not demonstrate improved outcomes because of early diagnosis of these tumors by routine screening.22
In contrast to the breast cancer screening recommendations for the general population,19, 23 those for childhood cancer survivors tend to be more rigorous. For example, the Children's Oncology Group recommends that childhood cancer patients who were treated with chest radiotherapy at a dose of ≥20 Gy during childhood, adolescence, or young adulthood should perform monthly breast self-examination, annual clinical breast examination until age 25 years and then every 6 months thereafter, and a yearly mammogram starting at age 25 years or 8 years after radiotherapy, whichever comes later.24 A recent report from the American Cancer Society recommends annual MRI screening in addition to mammography for women who received radiation to the chest between ages 10 and 30 years.25 Compared with other childhood cancer survivors of similar ages who had received either chest or mantle radiotherapy,11, 13 overall levels of breast cancer screening among Rb survivors were similar. The higher cancer screening levels for Rb survivors for Pap testing compared with other childhood cancer survivors may be explained in part by the higher attained mean age of Rb survivors (35 years vs 23 years).
Although retinoblastoma patients are not at a higher risk of testicular cancer compared with the general population, the proportion of Rb survivors practicing testicular self-examination (17.4%) was found to be similar to other reports of other childhood cancer survivors.26, 27 It should be noted, however, that not all investigators agree that testicular self-examination is an effective method for the early detection of testicular cancer.19, 28 This may explain the low prevalence of testicular self-examination in the current as well as other studies.
Limitations of the current study include self-reporting of all cancer screening without medical record validation or reason for screening, and lack of data regarding health insurance that would likely affect access to screening. It is possible that the survey respondents may have been healthier than the nonrespondents and as a result may have been more likely to take advantage of cancer screening. Alternatively, if a survivor had been diagnosed with another cancer, they may have been more likely to undergo annual cancer screening. Therefore, our data may overestimate the actual prevalence of cancer screening practices of Rb survivors. However, the prevalence of screening did not differ by hereditary status in this survey, despite 10% of hereditary and 1.8% of nonhereditary Rb survey respondents reporting a second cancer.
We did not inquire regarding the reason for mammography or whether a healthcare provider recommended it. For example, some mammograms may have been used to evaluate suspicious masses or to follow up on existing breast cancer rather than for routine screening. We hypothesized that the apparent increased risk for breast cancer in this cohort may have been due partially to more aggressive screening. However, only 1 of 11 breast cancers was stated to have been detected on a routine mammogram. Based on the size of the breast tumors, it appears that more intense screening is not likely to contribute to the increased risk of breast cancer in the cohort, because approximately half of the tumors were >5 cm in size when diagnosed.
Strengths of the current study include similar survey response rates for hereditary and nonhereditary Rb survivors, as well as no statistically significant differences detected in characteristics between responders and nonresponders. To our knowledge, the current study population is 1 of the largest existing cohorts of Rb survivors being studied over a long period of time. This group has attained a later age and a higher risk of adult cancers than most other studied cohorts of Rb patients.
Educating both survivors and healthcare professionals regarding potential second cancers is important. Various studies have shown that childhood cancer survivors lack accurate knowledge concerning their cancer diagnosis, treatment, and long-term health risks.11, 29–31 Therefore, it is important to ascertain whether those cancer survivors who are at the highest risk for developing certain second cancers are receiving the appropriate screening. In addition, knowledge regarding physician-guided screening, which we did not collect, would be useful in determining which groups of physicians need more education. According to a report evaluating the follow-up care of childhood cancer survivors in both the U.S. and U.K., primary care physicians are unfamiliar with the pediatric cancer survivor population.30 Raising awareness among these physicians of the unique health risks of cancer survivors could boost cancer screening and detection.29
This study establishes, to our knowledge, the first report of cancer screening behavior among Rb survivors in the U.S. Given the recent report that hereditary Rb survivors are at an increased risk for breast and other second cancers, these adult survivors, with the assistance of their physicians, should be encouraged to at least continue, if not increase, the level of cancer screening to ensure long-term health and overall quality of life.
REFERENCES
- 1.Ries LAG, Melbert D, Krapcho M, et al. Bethesda, MD: National Cancer Institute; 2006. [Accessed May 1, 2007]. SEER Cancer Statistics Review, 1975–2004. Available from URL: http://seer.cancer.gov/csr/1975_. [Google Scholar]
- 2.Draper GJ, Sanders BM, Kingston JE. Second primary neoplasms in patients with retinoblastoma. Br J Cancer. 1986;53:661–671. doi: 10.1038/bjc.1986.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Fletcher O, Easton D, Anderson K, et al. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst. 2004;96:357–363. doi: 10.1093/jnci/djh058. [DOI] [PubMed] [Google Scholar]
- 4.Kleinerman RA, Tucker MA, Tarone RE, et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol. 2005;23:2272–2279. doi: 10.1200/JCO.2005.05.054. [DOI] [PubMed] [Google Scholar]
- 5.Moll AC, Imhof SM, Bouter LM, et al. Second primary tumors in patients with hereditary retinoblastoma: a register- based follow-up study, 1945–1994. Int J Cancer. 1996;67:515–519. doi: 10.1002/(SICI)1097-0215(19960807)67:4<515::AID-IJC9>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
- 6.Hildreth NG, Shore RE, Dvoretsky PM. The risk of breast cancer after irradiation of the thymus in infancy. N Engl J Med. 1989;321:1281–1284. doi: 10.1056/NEJM198911093211901. [DOI] [PubMed] [Google Scholar]
- 7.Lundell M, Mattsson A, Karlsson P, et al. Breast cancer risk after radiotherapy in infancy: a pooled analysis of 2 Swedish cohorts of 17,202 infants. Radiat Res. 1999;151:626–632. [PubMed] [Google Scholar]
- 8.Lee EY, To H, Shew JY, et al. Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science. 1988;241:218–221. doi: 10.1126/science.3388033. [DOI] [PubMed] [Google Scholar]
- 9.T’Ang A, Varley JM, Chakraborty S, et al. Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science. 1988;242:263–266. doi: 10.1126/science.3175651. [DOI] [PubMed] [Google Scholar]
- 10.Varley JM, Armour J, Swallow JE, et al. The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours. Oncogene. 1989;4:725–729. [PubMed] [Google Scholar]
- 11.Diller L, Medeiros Nancarrow C, Shaffer K, et al. Breast cancer screening in women previously treated for Hodgkin’s disease: a prospective cohort study. J Clin Oncol. 2002;20:2085–2091. doi: 10.1200/JCO.2002.08.031. [DOI] [PubMed] [Google Scholar]
- 12.Kaste SC, Hudson MM, Jones DJ, et al. Breast masses in women treated for childhood cancer: incidence and screening guidelines. Cancer. 1998;82:784–792. doi: 10.1002/(sici)1097-0142(19980215)82:4<784::aid-cncr23>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- 13.Yeazel MW, Oeffinger KC, Gurney JG, et al. The cancer screening practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2004;100:631–640. doi: 10.1002/cncr.20008. [DOI] [PubMed] [Google Scholar]
- 14.Aziz NM, Rowland JH. Trends and advances in cancer survivorship research: challenge and opportunity. Semin Radiat Oncol. 2003;13:248–266. doi: 10.1016/S1053-4296(03)00024-9. [DOI] [PubMed] [Google Scholar]
- 15.Hawkins MM, Robison LL. Importance of clinical and epidemiological research in defining the long-term clinical care of pediatric cancer survivors. Pediatr Blood Cancer. 2006;46:174–178. doi: 10.1002/pbc.20609. [DOI] [PubMed] [Google Scholar]
- 16.Eng C, Li FP, Abramson DH, et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst. 1993;85:1121–1128. doi: 10.1093/jnci/85.14.1121. [DOI] [PubMed] [Google Scholar]
- 17.Wong FL, Boice JD, Jr, Abramson DH, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA. 1997;278:1262–1267. doi: 10.1001/jama.278.15.1262. [DOI] [PubMed] [Google Scholar]
- 18.Foster MC, Kleinerman RA, Abramson DH, et al. Tobacco use in adult long-term survivors of retinoblastoma. Cancer Epidemiol Biomarkers Prev. 2006;15:1464–1468. doi: 10.1158/1055-9965.EPI-05-0783. [DOI] [PubMed] [Google Scholar]
- 19.U.S. Preventive Services Task Force. The guide to clinical preventive services 2006. Washington, DC: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services; 2006. Jun, AHRQ Pub. No. 06-0588. [Google Scholar]
- 20.National Center for Health Statistics. Hyattsville, MD: National Center for Health Statistics; 2006. Health, United States, 2005, With Chartbook on Trends in the Health of Americans. [PubMed] [Google Scholar]
- 21.Rakowski W, Meissner H, Vernon SW, et al. Correlates of repeat and recent mammography for women ages 45 to 75 in the 2002 to 2003 Health Information National Trends Survey (HINTS 2003) Cancer Epidemiol Biomarkers Prev. 2006;15:2093–2101. doi: 10.1158/1055-9965.EPI-06-0301. [DOI] [PubMed] [Google Scholar]
- 22.Duncan JL, Scott IU, Murray TG, et al. Routine neuroimaging in retinoblastoma for the detection of intracranial tumors. Arch Ophthalmol. 2001;119:450–452. [PubMed] [Google Scholar]
- 23.Qaseem A, Snow V, Sherif K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007;146:511–515. doi: 10.7326/0003-4819-146-7-200704030-00007. [DOI] [PubMed] [Google Scholar]
- 24.Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. [Accessed June 15, 2007];Version 2.0. 2006 Mar; Available from URL: http://www.survivorshipguidelines.org. [Google Scholar]
- 25.Saslow D, Boetes C, Burke W, et al. American cancer society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89. doi: 10.3322/canjclin.57.2.75. [DOI] [PubMed] [Google Scholar]
- 26.Castellino SM, Casillas J, Hudson MM, et al. Minority adult survivors of childhood cancer: a comparison of long-term outcomes, health care utilization, and health-related behaviors from the childhood cancer survivor study. J Clin Oncol. 2005;23:6499–6507. doi: 10.1200/JCO.2005.11.098. [DOI] [PubMed] [Google Scholar]
- 27.Hudson MM, Tyc VL, Srivastava DK, et al. Multi-component behavioral intervention to promote health protective behaviors in childhood cancer survivors: the protect study. Med Pediatr Oncol. 2002;39:1–2. doi: 10.1002/mpo.10071. discussion, 2. [DOI] [PubMed] [Google Scholar]
- 28.Buetow SA. Testicular cancer: to screen or not to screen? J Med Screen. 1996;3:3–6. doi: 10.1177/096914139600300103. [DOI] [PubMed] [Google Scholar]
- 29.Landier W, Wallace WH, Hudson MM. Long-term follow-up of pediatric cancer survivors: education, surveillance, and screening. Pediatr Blood Cancer. 2006;46:149–158. doi: 10.1002/pbc.20612. [DOI] [PubMed] [Google Scholar]
- 30.Oeffinger KC, Wallace WH. Barriers to follow-up care of survivors in the United States and the United Kingdom. Pediatr Blood Cancer. 2006;46:135–142. doi: 10.1002/pbc.20614. [DOI] [PubMed] [Google Scholar]
- 31.Skinner R, Wallace WH, Levitt GA. Long-term follow-up of people who have survived cancer during childhood. Lancet Oncol. 2006;7:489–498. doi: 10.1016/S1470-2045(06)70724-0. [DOI] [PubMed] [Google Scholar]