Breast cancer in Wilms tumor survivors: New insights into primary and secondary prevention

Abstract

The treatment of Wilms tumor (WT) is one of the great success stories in the field of oncology. Five-year overall survival (OS) estimates are 90% using modern treatment regimens, including surgery, chemotherapy, and radiotherapy (RT). 1 However, WT survivorship comes at a cost, as meticulously demonstrated by the Childhood Cancer Survivor Study (CCSS) and the National Wilms Tumor Late Effects Study (NWTS). [2][3][4] In the CCSS cohort, the cumulative incidence of chronic health conditions among survivors of WT was 65% at 25 years after WT diagnosis. WT survivors had an incidence of severe (grade 3 and 4, according to the National Cancer Institute Common Terminology Criteria for Adverse Events grading system) chronic health conditions that was 4.7 times that of their sibling comparison group.2 Common chronic health conditions included congestive heart failure, renal failure, and hypertension. Subsequent malignant neoplasms (SMNs) are another well-documented late complication of WT therapy. In the CCSS cohort of 1256 survivors of WT, the cumulative incidence of SMNs was 3.0% at 25 years from the time of WT diagnosis, with the most common being soft tissue sarcoma (6 cases) and breast cancer (5 cases).2 In a previously reported NWTS cohort of 5287 survivors of WT, the cumulative incidence of SMNs was 1.6% at 15 years after WT diagnosis. 5The most common SMNs were carcinomas (13 cases), sarcomas (13 cases), and leukemias (9 cases); 3 cases of breast cancer were observed. In a combined international cohort of 13,351 survivors of WT, a cumulative risk of second solid tumors of 6.7% at age 40 years was observed; 23 survivors in this cohort had breast cancer. 6The article by Lange et al in this issue of Cancer describes what appears to be the largest number of breast cancer cases among survivors of WT reported to date and sheds light on measures that can be taken for both primary and secondary prevention. 7 The study included a total of 2492 female survivors of WT who were enrolled on one of the first 4 NWTS trials . Twenty-nine cases of invasive breast cancer were identified among 28 patients. The median age at the time of first breast cancer diagnosis was 34.3 years (range, 15.5 years-48.4 years) and the median time from WT diagnosis to breast cancer diagnosis was 27.1 years (range, 7.9 years-35.7 years). The estimated cumulative risk of breast cancer at age 40 years (CR40) for all female survivors of WT was 4.5% (95% confidence interval [95% CI], 2.8-7.2), with a standardized incidence ratio (SIR) of 9.1 (95% CI, 6.0-13.0) compared with the general US population. The risk of breast cancer was most pronounced in the cohort of patients who received chest RT, with a CR40 of 14.8% (95% CI, 8.7%-24.5%) and an SIR of 27.4 (95% CI, 16.1-44.2). It is interesting to note that the risk of breast cancer was elevated compared with the general population in patients who received abdominal RT only, with a CR40 of 3.1% (95% CI, 1.3%-7.1%) and an SIR of 6.0 (95% CI, 2.9-11.0). This SIR was not statistically significantly different f...

Wilms tumor and breast cancer

“…Malignant tumors are a well-documented late complication of therapy for Wilms tumor. 1 Lange et al reported that female survivors of Wilms tumor who were treated with radiotherapy to the thorax at a dose of 12 to 14 gray (Gy) had an elevated risk of developing early breast cancer, with nearly 15% having invasive disease by age 40 years. 2 Radiotherapy to the thorax is a risk factor for male breast cancer as well.…”

“…Males account for <1% of breast cancers diagnosed in the United States, and the disease is especially rare in younger men. 1 Using data from the 9th (1973-1991), 13th (1992-1999), and 18th (2000-2010) Surveillance, Epidemiology, and End Results registries, we calculated incidence rates of invasive plus in situ breast cancer for men and women aged <40 years of 0.0433 and 13.99 per 100,000 person-years, respectively. This yielded a male:female (M:F) ratio of 0.0031.…”

Reply to Wilms tumor and breast cancer

“…We thank Drs. Lehrer and Rosenzweig for their insightful comments and opportunity to expand on our discussion regarding breast cancer in survivors of Wilms tumor . We acknowledge that the development of breast cancer in men was not specifically addressed in our comments.…”