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Malignant Breast Tumors After Radiotherapy for a First Cancer During Childhood
In summary, the finding by Buist and colleagues that annual screening intervals for women aged 40-49 reduced the relative influence of faster tumor growth rates on mammographic sensitivity is consistent with the conclusions of many earlier studies.1,2, 7-10 On the basis of these studies, both the American Cancer Society and the American College of Radiology in 1997 changed their recommended frequency for screening women aged 40-49 years from every 1-2 years to every year.11,12
References 1. Moskowitz M: Breast cancer: Age-specific growth rates and screening strategies. Radiology 161:37-41, 1986. 2. Tabar L, Fagerberg G, Day NE, et al: What is the optimum interval between screening examinations? An analysis based on the latest results of the Swedish Two-County breast cancer screening trial. Br J Cancer 55:547-551, 1987. 3. Smart CR, Hendrick RE, Rutledge JH III, et al: Benefit of mammography screening in women ages 40-49 years: Current evidence from randomized controlled trials. Cancer 75:16191626, 1995. 4. Hendrick RE, Smith RA, Rutledge JH III, et al: Benefit of screening mammography in women aged 40-49: A new metaanalysis of randomized controlled trials. J Natl Cancer Inst Monogr 22:87-92, 1997.
graphic screening program. J Natl Cancer Inst Monogr 22:6368, 1997. 6. Bjurstam N, Bjorneld L, Duffy SW, et al: The Gothenburg breast screening trial: First results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization. Cancer 80:2091-2099, 1997. 7. Organizing Committee and Collaborators, Falun Meeting: Breast-cancer screening with mammography in women aged 40-49 years. Int J Cancer 68:693-699, 1996. 8. Feig SA: Estimation of currently attainable benefit from mammographic screening of women aged 40-49 years. Cancer 75:2412-2419, 1995. 9. Feig SA: Increased benefit from shorter screening mammography intervals for women ages 40-49 years. Cancer 80:20352039, 1997. 10. Feig SA: Determination of mammographic screening intervals with surrogate measures for women aged 40-49 years. Radiology 93:311-314, 1994. 11. Leitch AM, Dodd GD, Costanza M, et al: American Cancer Society guidelines for the early detection of breast cancer. Update 1997. CA Cancer J Clin 47:150-153, 1997. 12. Feig SA, D’Orsi CJ, Hendrick RE, et al: American College of Radiology Guidelines for Breast Cancer Screening. AJR Am J Roentgenol 171:29-33, 1998.
5. Andersson I, Janzon L: Reduced breast cancer mortality in women under 50: Updated results from the Malmo mammo-
Malignant Breast Tumors After Radiotherapy for a First Cancer During Childhood David B. Mansur, MD Whether considering radium watch-dial painters, atomic bomb survivors, patients with tuberculosis after multiple fluoroscopies, or patients with tinea capitis treated with x-rays, the strong correlation between exposure to ionizing radiation and carcinogenesis has been apparent for decades. Towards the end of the 20th century, another correlation was observed between having survived a cancer in childhood and the incidence of developing a subsequent cancer. The common conclusion has been that this increase in risk of a second cancer results from exposure to therapeutic ionizing radiation. The true causation, however, is more complicated when additional factors are considered, including exposure to carcinogenic chemotherapeutic
324 324
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Breast Diseases: A Year Book Quarterly Vol 16 No 4 2006
agents and, perhaps most importantly, genetic susceptibility in this potentially “cancer-prone” population. These issues were addressed in the thorough study by Guibout and colleagues (see Abstract 4–31), which attempted to establish a radiation dose-response for subsequent occurrence of breast cancer in survivors of childhood nonleukemia cancers. Their cohort of 1,814 women included 1,258 who had received radiation therapy, with the average dose per breast estimated as 5.06 Gy. The average follow-up time was 16 years from the time the first cancer was diagnosed, with 25% of the cohort having been followed for 20 years or more. Sixteen patients developed an invasive breast cancer; the cumulative incidence of 5.1% at the age of 40 years represented 16.9 times the anticipated rate in then general population. Radiation therapy was associated with a statistically insignificant increase in breast cancer risk when it was considered as a dichotomous variable: 13 patients (1.03%) who had undergone irradiation developed an invasive breast cancer as compared with 3 patients (0.54%) who had not undergone irradiation. However, a trend toward an increase in breast
cancer with increasing radiation dose was identified for doses up to 20 Gy. Interestingly, a trend was also seen toward increased risk of breast cancer for patients given nucleotide synthesis inhibitors. Most importantly, having had Hodgkin’s disease as the first cancer predicted a significantly higher rate of subsequent breast cancer. What is clear in this study was the high relative risk of developing breast cancer in female survivors of childhood cancer.
This increased risk was evident even though the follow-up period was relatively short at a mean of 16 years. Unfortunately, this study suffered from a small sample size, which limits the ability to reach conclusions regarding causation. Studies with larger numbers of patients are needed to scrutinize the relative influences of genetic susceptibility and exposure to a wide range of carcinogenic cancer therapies on risk of developing a subsequent breast cancer.
Breast Cancer in African-American Women: Summary of the Evidence
40,000 white women with breast cancer revealed that AA ethnicity was the independent predictor of higher mortality.4 Alternative means of evaluating socioeconomic status in the context of culture, social networks, and environment are necessary to provide improved insights regarding the cancer burden of the poor in our society. Moreover, recent investigations into poorly understood disparities in the delivery of care to ethnic minorities and female patients5-7 raise the concern that subtle provider-level biases may affect breast cancer outcome as well. The threat of increased breast cancer mortality among AA women can be explained in part by the fact that the disease tends to be at more advanced stages at diagnosis among AA women than among WA women—for example, roughly one quarter (28%) of white breast cancer patients present with node-positive disease as compared with about one third (35%) of AA patients.1 On the other hand, numerous analyses of SEER data have revealed persistent survival disadvantages among AA patients even after controlling for stage of disease at presentation. Edwards and colleagues8 analyzed SEER data to assess survival in AA and white women with breast cancer after stratification for node status (positive vs negative); in that 1998 report, the AA background was found to have a significant and independent adverse effect on the likelihood of being “cured” of disease. In another study of SEER data, Li and colleagues9 found that survival was worse among AA women with breast cancer even after the data were adjusted for stage, treatment, and a variety of ethnic/racial backgrounds. The most disturbing reports from the SEER analyses, however, are recent ones focusing on outcome in women presenting with either small invasive tumors or ductal carcinoma in situ. These reports suggested that being AA has a negative effect on relapse rates despite the fact that these tumors are generally associated with a favorable prognosis. In a study reported in abstract form in 2003, Blake and colleagues10 looked at SEER cases of T1 tumors diagnosed between 1990 and 1994 and found that being AA was associated with significantly higher risks of having estrogen receptor–
Lisa A. Newman, MD, MPH Disparities in breast cancer outcome associated with ethnic background in the United States have been documented in population-based data reported by the Surveillance, Epidemiology, and End Results (SEER) Program over the past 3 decades.1 The magnitude of ethnicity-associated differences in breast cancer incidence and mortality is greatest in comparisons between African American (AA) and white women in the United States. Variations in the impact of breast cancer in AA and white women have also generated significant attention because of their complex and multifactorial nature. The lifetime incidence of breast cancer is lower among AA women than in white women, yet paradoxically mortality rates from breast cancer are higher in the AA population. Recent SEER statistics indicate an age-adjusted breast cancer incidence rate of 141 per 100,000 for white women, as opposed to 122 per 100,000 for AA women. However, the mortality rate from breast cancer is higher in AA women than in white women (35.9 vs 27.2 per 100,000), and the 5-year survival rates are 87.9% for white women but only 73.5% for AA patients with breast cancer.1 Possible causes of these disparities include differences in the prevalence of disadvantages associated with socioeconomic status; for example, being underinsured or completely uninsured and living with incomes in the poverty range are twice as high among AA communities as in white communities in the United States.2,3 These disadvantages act as barriers to health care access and are likely to increase the risk of mortality from a variety of comorbid conditions. Single-institution studies generally lack sufficient statistical power to attempt to address the question of whether AA ethnicity acts as a surrogate for inadequate medical care secondary to lack of socioeconomic resources. A pooled analysis of survival, adjusted for socioeconomic status, in more than 10,000 AA women and more than
®
Breast Diseases: A Year Book Quarterly Vol 16 No 4 2006
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References 1. Moskowitz M: Breast cancer: Age-specific growth rates and screening strategies. Radiology 161:37-41, 1986. 2. Tabar L, Fagerberg G, Day NE, et al: What is the optimum interval between screening examinations? An analysis based on the latest results of the Swedish Two-County breast cancer screening trial. Br J Cancer 55:547-551, 1987. 3. Smart CR, Hendrick RE, Rutledge JH III, et al: Benefit of mammography screening in women ages 40-49 years: Current evidence from randomized controlled trials. Cancer 75:16191626, 1995. 4. Hendrick RE, Smith RA, Rutledge JH III, et al: Benefit of screening mammography in women aged 40-49: A new metaanalysis of randomized controlled trials. J Natl Cancer Inst Monogr 22:87-92, 1997.
graphic screening program. J Natl Cancer Inst Monogr 22:6368, 1997. 6. Bjurstam N, Bjorneld L, Duffy SW, et al: The Gothenburg breast screening trial: First results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization. Cancer 80:2091-2099, 1997. 7. Organizing Committee and Collaborators, Falun Meeting: Breast-cancer screening with mammography in women aged 40-49 years. Int J Cancer 68:693-699, 1996. 8. Feig SA: Estimation of currently attainable benefit from mammographic screening of women aged 40-49 years. Cancer 75:2412-2419, 1995. 9. Feig SA: Increased benefit from shorter screening mammography intervals for women ages 40-49 years. Cancer 80:20352039, 1997. 10. Feig SA: Determination of mammographic screening intervals with surrogate measures for women aged 40-49 years. Radiology 93:311-314, 1994. 11. Leitch AM, Dodd GD, Costanza M, et al: American Cancer Society guidelines for the early detection of breast cancer. Update 1997. CA Cancer J Clin 47:150-153, 1997. 12. Feig SA, D’Orsi CJ, Hendrick RE, et al: American College of Radiology Guidelines for Breast Cancer Screening. AJR Am J Roentgenol 171:29-33, 1998.
5. Andersson I, Janzon L: Reduced breast cancer mortality in women under 50: Updated results from the Malmo mammo-
Malignant Breast Tumors After Radiotherapy for a First Cancer During Childhood David B. Mansur, MD Whether considering radium watch-dial painters, atomic bomb survivors, patients with tuberculosis after multiple fluoroscopies, or patients with tinea capitis treated with x-rays, the strong correlation between exposure to ionizing radiation and carcinogenesis has been apparent for decades. Towards the end of the 20th century, another correlation was observed between having survived a cancer in childhood and the incidence of developing a subsequent cancer. The common conclusion has been that this increase in risk of a second cancer results from exposure to therapeutic ionizing radiation. The true causation, however, is more complicated when additional factors are considered, including exposure to carcinogenic chemotherapeutic
324 324
®
Breast Diseases: A Year Book Quarterly Vol 16 No 4 2006
agents and, perhaps most importantly, genetic susceptibility in this potentially “cancer-prone” population. These issues were addressed in the thorough study by Guibout and colleagues (see Abstract 4–31), which attempted to establish a radiation dose-response for subsequent occurrence of breast cancer in survivors of childhood nonleukemia cancers. Their cohort of 1,814 women included 1,258 who had received radiation therapy, with the average dose per breast estimated as 5.06 Gy. The average follow-up time was 16 years from the time the first cancer was diagnosed, with 25% of the cohort having been followed for 20 years or more. Sixteen patients developed an invasive breast cancer; the cumulative incidence of 5.1% at the age of 40 years represented 16.9 times the anticipated rate in then general population. Radiation therapy was associated with a statistically insignificant increase in breast cancer risk when it was considered as a dichotomous variable: 13 patients (1.03%) who had undergone irradiation developed an invasive breast cancer as compared with 3 patients (0.54%) who had not undergone irradiation. However, a trend toward an increase in breast
cancer with increasing radiation dose was identified for doses up to 20 Gy. Interestingly, a trend was also seen toward increased risk of breast cancer for patients given nucleotide synthesis inhibitors. Most importantly, having had Hodgkin’s disease as the first cancer predicted a significantly higher rate of subsequent breast cancer. What is clear in this study was the high relative risk of developing breast cancer in female survivors of childhood cancer.
This increased risk was evident even though the follow-up period was relatively short at a mean of 16 years. Unfortunately, this study suffered from a small sample size, which limits the ability to reach conclusions regarding causation. Studies with larger numbers of patients are needed to scrutinize the relative influences of genetic susceptibility and exposure to a wide range of carcinogenic cancer therapies on risk of developing a subsequent breast cancer.
Breast Cancer in African-American Women: Summary of the Evidence
40,000 white women with breast cancer revealed that AA ethnicity was the independent predictor of higher mortality.4 Alternative means of evaluating socioeconomic status in the context of culture, social networks, and environment are necessary to provide improved insights regarding the cancer burden of the poor in our society. Moreover, recent investigations into poorly understood disparities in the delivery of care to ethnic minorities and female patients5-7 raise the concern that subtle provider-level biases may affect breast cancer outcome as well. The threat of increased breast cancer mortality among AA women can be explained in part by the fact that the disease tends to be at more advanced stages at diagnosis among AA women than among WA women—for example, roughly one quarter (28%) of white breast cancer patients present with node-positive disease as compared with about one third (35%) of AA patients.1 On the other hand, numerous analyses of SEER data have revealed persistent survival disadvantages among AA patients even after controlling for stage of disease at presentation. Edwards and colleagues8 analyzed SEER data to assess survival in AA and white women with breast cancer after stratification for node status (positive vs negative); in that 1998 report, the AA background was found to have a significant and independent adverse effect on the likelihood of being “cured” of disease. In another study of SEER data, Li and colleagues9 found that survival was worse among AA women with breast cancer even after the data were adjusted for stage, treatment, and a variety of ethnic/racial backgrounds. The most disturbing reports from the SEER analyses, however, are recent ones focusing on outcome in women presenting with either small invasive tumors or ductal carcinoma in situ. These reports suggested that being AA has a negative effect on relapse rates despite the fact that these tumors are generally associated with a favorable prognosis. In a study reported in abstract form in 2003, Blake and colleagues10 looked at SEER cases of T1 tumors diagnosed between 1990 and 1994 and found that being AA was associated with significantly higher risks of having estrogen receptor–
Lisa A. Newman, MD, MPH Disparities in breast cancer outcome associated with ethnic background in the United States have been documented in population-based data reported by the Surveillance, Epidemiology, and End Results (SEER) Program over the past 3 decades.1 The magnitude of ethnicity-associated differences in breast cancer incidence and mortality is greatest in comparisons between African American (AA) and white women in the United States. Variations in the impact of breast cancer in AA and white women have also generated significant attention because of their complex and multifactorial nature. The lifetime incidence of breast cancer is lower among AA women than in white women, yet paradoxically mortality rates from breast cancer are higher in the AA population. Recent SEER statistics indicate an age-adjusted breast cancer incidence rate of 141 per 100,000 for white women, as opposed to 122 per 100,000 for AA women. However, the mortality rate from breast cancer is higher in AA women than in white women (35.9 vs 27.2 per 100,000), and the 5-year survival rates are 87.9% for white women but only 73.5% for AA patients with breast cancer.1 Possible causes of these disparities include differences in the prevalence of disadvantages associated with socioeconomic status; for example, being underinsured or completely uninsured and living with incomes in the poverty range are twice as high among AA communities as in white communities in the United States.2,3 These disadvantages act as barriers to health care access and are likely to increase the risk of mortality from a variety of comorbid conditions. Single-institution studies generally lack sufficient statistical power to attempt to address the question of whether AA ethnicity acts as a surrogate for inadequate medical care secondary to lack of socioeconomic resources. A pooled analysis of survival, adjusted for socioeconomic status, in more than 10,000 AA women and more than
®
Breast Diseases: A Year Book Quarterly Vol 16 No 4 2006
325 325