Female survivors of Wilms tumor may be at increased risk for breast cancer

Women who survived Wilms tumor, particularly those who underwent chest radiotherapy, demonstrated increased risk for invasive breast cancer by age 40 years, according to study results.

Norman E. Breslow, PhD, of the department of biostatistics at the University of Washington, and colleagues evaluated 2,492 women from the United States and Canada enrolled in one of the first four protocols of the National Wilms Tumor Study (NWTS), conducted between 1969 and 1995.

Norman E. Breslow

All participants were diagnosed with Wilms tumor between birth and age 19 years.

Follow-up continued from age 15 or 5 years after Wilms tumor onset, whichever was later, until last contact or death.

About half of the women (50.6%) underwent radiotherapy as part of their treatment for Wilms tumor.

In the first protocol, patients underwent radiotherapy in uniform doses of 14 Gy for pulmonary metastasis. The dosage was modified to 12 Gy for the second, third and fourth protocols. Treatment volume encompassed the entire chest, from roughly the clavicle to the L1 vertebra, irrespective of the number and location of detectable metastases.

Abdominal doses of radiotherapy varied, and intensified chemotherapy replaced radiotherapy in later protocols.

Breslow and colleagues determined 16 of 369 women who underwent chest radiotherapy developed invasive breast cancer by age 40 years, equating to a cumulative risk of 14.8% (95% CI, 8.7-24.5). Ten of 894 women who underwent abdominal radiotherapy only developed breast cancer by age 40 years, equating to a cumulative risk of 3.1% (95% CI, 1.3-7.41). Two of 1,229 women who did not undergo radiotherapy developed breast cancer by age 40 years, equating to a cumulative risk of 0.3% (95% CI, 0-2.3).

The standardized incidence ratio (SIR) for women who underwent chest radiotherapy was 27.6 (95% CI, 16.1-44.2) based on 5,010 person-years of follow-up. The SIR for those who underwent abdominal radiotherapy only was 6 (95%, 2.9-11) based on 13,185 person-years of follow-up, and the SIR for those who did not undergo radiotherapy was 2.2 (95% CI, 0.3-7.8) based on 13,560 person-years of follow-up.

Among women diagnosed with Wilms tumor at age 10 years or older, the risk for breast cancer was elevated regardless of receipt of chest radiotherapy. In that subset, nine of 90 women developed breast cancer by age 40 years, equating to a cumulative incidence of 13.5% (95% CI, 5.6-30.6) and a SIR of 23.6 (95% CI, 10.8-44.8) based on 1,463 person-years of follow-up.

The findings show pediatric oncologists must be more vigilant in their management of Wilms tumor survivors who may be at risk for breast cancer later in life, Jennifer B. Dean, MD, and Jeffrey S. Dome, MD, PhD, both of Children’s National Health System, wrote in an accompanying editorial.

“The take-home message is that pediatric oncology providers should closely evaluate their female survivors of Wilms tumor for risk factors for the development of breast cancer, including chest radiotherapy (even at doses <20 Gy), age >10 years at the time of Wilms tumor diagnosis and, possibly, flank radiotherapy that may have involved breast tissue,” Dean and Dome wrote. “Those deemed to be at high risk should undergo breast cancer surveillance with mammography, breast MRI or both starting at age 25 years.

“Further research is needed to define the optimal imaging modality and to refine which survivors are the most appropriate candidates for surveillance,” they added. “Because compliance with breast cancer surveillance is low among adult survivors of childhood cancer, barriers such as education of both survivors and providers should be addressed and mitigated.”

For more information:

Lange JM. Cancer. 2014; DOI: 10.1002/cncr.28908
Dean JB. Cancer. 2014; DOI: 10.1002/cncr.28906

Disclosure: The researchers report no relevant financial disclosures. Dean and Dome report no relevant financial disclosures.