Women who survived cancer when they were children are four times more likely to develop early breast cancer as adults than those who did not have cancer as a child, even if they never received radiation therapy to the chest.
According to a study published December 21, 2015, in the Journal of Clinical Oncology, 85 percent of the increase was caused by two specific cancer types: sarcoma, a cancer of the connective tissues, and leukemia, a cancer of the blood. The women in this study who survived childhood sarcoma were 5.3 times more likely than average to have a breast cancer diagnosis. The women treated for leukemia were 4.1 times more likely.
“Two classes of chemotherapy, anthracyclines and alkylators, appear to be associated with this increase,” said the study’s lead author, Tara Henderson, MD, MPH, associate professor of pediatrics and director of the Childhood Cancer Survivors Center at the University of Chicago Medicine.
Both of these medications are used to treat many kinds of cancer. They work by causing cause genetic damage to cancer cells, but they are toxic to normal cells as well, particularly those that divide frequently, such as bone marrow and the cells that line the gastrointestinal tract. Many of these agents are also carcinogenic.
In this study, women exposed to high doses of alkylator or anthracycline chemotherapy as children were almost 10 times more likely to be diagnosed with breast cancer in their 20s, 30s or early 40s than women who have never been diagnosed or treated for cancer.
“This is the first time such an increase has been reported in a large study of patients who did not receive radiation to the chest but were exposed to these agents,” Henderson said. The data suggest there is “a relationship between higher doses of anthracyclines and alkylators and greater risk of subsequent breast cancer.”
The researchers reviewed the records of 3,768 women diagnosed with a childhood cancer between 1970 and 1986 who survived at least 5 years. None of the women in the study—which involved 26 leading centers in North America, all part of the Childhood Cancer Survivor Study—received radiation therapy to the chest, a known cause of increased breast cancer risk.
The researchers found that 47 of these women developed breast cancer 10 to 34 years after their first cancer. The median age for diagnosis was 38 years, much younger than normal. These women were more likely to have cancer in both breasts.
Risk was highest among women who had been treated for sarcoma or leukemia. Twenty-six of those 47 women (55%) were treated for sarcoma as children and 14 (30%) were treated for leukemia.
Women who were between the ages of 10 and 20 when they were diagnosed with childhood cancer were also more likely to get breast cancer at a relatively young age.
By the age of 45, 4.5 percent of the women in the study had developed breast cancer. Some developed breast cancer as early as age 22. The highest rates by age 45 were 6.3 percent of childhood cancer survivors with leukemia and 5.8 percent of those with sarcoma. Each group was more than twice as likely to develop cancer as the other survivors.
The study had several limitations, the authors note. It included a relatively small number of patients who developed second cancers. The researchers had limited information about family history of cancer risk. They also lacked detailed knowledge about radiation exposure for patients from X-rays or CT scans utilized, for example, for surveillance for recurrence of the primary cancer.
Despite these limitations, the researchers encourage women who were treated for cancer as children to have regular screenings for any complications of earlier treatment, including heart and lung disease as well as cancer.
They also suggest that clinicians should consider whether all survivors, and in particular survivors of sarcoma and leukemia, should obtain a detailed family history of cancer and consider genetic counseling and testing where warranted. Clinicians should counsel women who have an increased familial risk or genetic predisposition to breast cancer to initiate breast cancer surveillance that includes more frequent mammograms, starting at an earlier age, and possibly additional screening techniques such as breast MRI.