Zosia Chustecka

June 04, 2012

June 4, 2012 — Among survivors of childhood cancer who were treated with radiotherapy to the chest, the risk of developing breast cancer is higher than was previously thought. New data suggest that recommendations for screening should cast a wider net to catch more of these people.

Currently, the Children's Oncology Group recommends that women who received chest radiation with 20 Gy or more be screened annually for breast cancer, using both mammography and breast magnetic resonance imaging, starting at 25 years of age or 8 years after receiving the radiotherapy.

However, new data, presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), show that women who received lower doses of radiation (from 10 to 19 Gy) are also at high risk of developing breast cancer.

"These women also have a substantially elevated risk of breast cancer," said lead author Chaya Moskowitz, PhD, biostatistician at Memorial Sloan-Kettering Cancer Center in New York City. "It is remarkable that there is no recommendation for screening in this group," she added.

The researchers estimate that some 50,000 women in the United States have been treated with chest radiation of 20 Gy or higher, and that another 7000 to 9000 have been treated with 10 to 19 Gy.

"The benefit of curing a cancer is that these survivors can live for 25 years or more. We have an obligation to these thousands of young women we treated all those years ago, and we have to look again at how they should be followed-up and screened," said Nicholas Vogelzang, MD, chair of the ASCO Cancer Communications Committee and medical director at the US Oncology Comprehensive Cancer Centers of Nevada.

"These are rather striking data," he said at a press briefing, and "they warrant our careful attention to improve follow-up of these cancer survivors."

Comparable to Risk in BRCA1 Carriers

The risk for breast cancer after chest radiation is well recognized; it led to the discontinuation in the mid-1990s of mantle radiation, which exposes the entire chest region, Dr. Moskowitz explained. The doses used for chest irradiation have been decreasing in recent years, but this study shows that even the lower doses increase the risk, she said at a press briefing.

Dr. Moskowitz and colleagues analyzed data from more than 1200 female childhood cancer survivors participating in the Childhood Cancer Survivor Study (CCSS) and 4570 female first-degree relatives of women participating in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study.

They found that, overall, women who had received radiation to the chest for the treatment of a childhood cancer (at a median age of 16 years) had a 24% risk of having breast cancer the time they reached the age of 50.

For a subgroup of women who had had Hodgkin's lymphoma (about half of the group) and who had received higher doses of chest radiation, the risk for breast cancer was 30% by the age of 50.

This is similar to the 31% risk seen in carriers of the BRCA1 mutation; for these patients, the recommended management includes the option of bilateral prophylactic mastectomy, said Maureen O'Brien MD, from the Cincinnati Children's Hospital Medical Center in Ohio, who acted as a discussant for the study.

In comparison, women with BRCA2 mutations have a 10% risk of developing breast cancer by the time they reach the age of 50; women in the general population have a 4% risk at that age.

A critical take-home message from this study is that the cut-off point of 20 Gy might be inappropriate, Dr. O'Brien said. These data show a risk with doses in the region of 10 to 19 Gy, which is "disheartening," she said, because doses of 15 Gy are currently widely used.

Dr. O'Brien revisited the ongoing controversy of whether radiation is absolutely necessary in the treatment of Hodgkin's lymphoma. She reviewed data suggesting that more intensive chemotherapy without radiation is a reasonable first-line approach, with radiation added if necessary on relapse. She asked: "Should we eliminate radiotherapy for more patients and accept a higher relapse rate, and then use salvage therapy?"

Challenges of Survivor Care

Other data that Dr. O'Brien highlighted in her discussion suggest that current surveillance of cancer survivors is inadequate. A study published in JAMA (2009;301:404-414) found that only 55% of female childhood cancer survivors had ever had a screening mammogram, and that 47% of those younger than 40 years had never had one.

In addition, a study being presented at the meeting shows that primary care physicians, who generally end up caring for cancer survivors, are not following guidelines. When presented with a vignette of a 29-year-old woman treated for Hodgkin's lymphoma with mantle radiation at the age of 16, only 29% of the primary care physicians surveyed said they would screen for breast cancer (abstract 9586). Another study, this time surveying childhood cancer survivors, found that less than one third reported receiving survivorship-focused care (abstract 6027).

Dr. Moskowitz and Dr. O'Brien have disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract CRA9513. Presented June 4, 2012.

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