Breast Cancer Surveillance Recommended When Chest Irradiated for Cancer Early in Life

Nick Mulcahy

April 06, 2010

April 6, 2010 — Women treated with chest radiation for cancer during childhood, adolescence, or young adulthood have a substantially elevated risk for breast cancer at a relatively young adult age, according to a new systematic review on the subject.

The increased risk is found as early as 8 years after chest radiation and does "not plateau with increasing length of follow-up," according to the review authors, led by Kevin C. Oeffinger, MD, director of the Adult Long-Term Follow-Up Program in the Departments of Pediatrics and Medicine at the Memorial Sloan-Kettering Cancer Center in New York City.

The cumulative incidence of breast cancer by 40 to 45 years in these women ranged from 13% to 20%.

This incidence is similar to that in women with a BRCA gene mutation.

"This incidence is similar to that in women with a BRCA gene mutation," write Dr. Oeffinger and his colleagues from the Children's Oncology Group (COG).

The review, which is published in the April 6 issue of the Annals of Internal Medicine, noted that about two thirds of these women were initially treated for Hodgkin's lymphoma. Their breast cancer risk increased linearly with the dose of the earlier chest radiation.

The COG reports that "there seems to be a benefit from early detection" in these patients. Thus, when there is radiation of 20 Gy or more early in life, the COG recommends annual surveillance mammography and magnetic resonance imaging (MRI) starting either at the age of 25 years or 8 years after completion of radiation therapy, whichever occurred last.

Nevertheless, this approach to annual surveillance is a recommendation with caveats.

"Too little is understood about the potential harms," write the COG authors about screening-related false-positives, additional unnecessary testing and biopsies, and the emotional and economic costs.

And there is also the matter of giving more radiation to these women via mammograms.

"Another potential harm is the additional risk for radiation-induced breast cancer," write the authors.

A standard 2-view mammogram exposes a woman to about 3.85 mGy.

"A standard 2-view mammogram exposes a woman to about 3.85 mGy," Dr. Oeffinger told Medscape Oncology.

Women who start receiving surveillance at the age of 25 would have at least 15 more mammographies than women who undergo usual screening, which begins at the age of 40, note the authors.

However, as the COG authors note, findings from researchers who have looked at the "detected-induced [breast cancer] ratio" from mammography are probably not applicable to the population of women treated with high doses of therapeutic radiation. In short, the ratio is unknown.

"Further research is required to better define the harms and benefits of lifelong surveillance," say the authors about the variety of unknowns, including the effects of mammography-related radiation exposure.

Still, given the COG recommendation for these women to start early surveillance with mammography and MRI, these experts endorse annual screening. "Limited evidence indicates that specialized surveillance will benefit this high-risk population," they write.

Study Findings and the Need to Intervene

Clinicians who want to discuss breast cancer risk and surveillance with these women first need to know the history of chest radiation for cancer during childhood, adolescence, and young adulthood.

The women need to know it too, write the study authors, so "interventions" are needed.

At Memorial Sloan-Kettering, women are provided with a summary of their earlier cancer treatment and risks, and a recommendation for surveillance, according to Dr. Oeffinger. "We give our patients a 1-page summary with this information and discuss it with them. The surveillance rate of our women exceeds 90%," he said.

To assess breast cancer risk in this population, Dr. Oeffinger and his COG colleagues looked at 11 retrospective cohort studies and 3 case–control studies. The cohort studies consisted of more than 14,000 women, 7,000 of whom received chest radiation for some kind of cancer before the year 2000. There were 422 women who subsequently developed breast cancer.

Among the "higher-quality" cohort studies, the standardized incidence ratio ranged from 13.3 to 55.5 per 10,000 person-years, and the absolute excess risk ranged from 18.6 to 79.0 per 10,000 person-years.

One of the case–control studies found that, among women who received a diagnosis of Hodgkin's lymphoma at the age of 15 and were counseled to undergo screening at the age of 25, 9.2% of those who received 20 to 39 Gy and 11.1% of those who received 40 Gy or more would develop breast cancer by the age 45.

Receiving radiation to the chest for cancer in childhood is not protective, compared with receiving radiation in adolescence, observe the authors.

"Risk in women treated before puberty is not lower than that in those treated during adolescence, as suggested by some early studies," they write. Studies with extended years of follow-up have not found a difference in breast cancer risk between women treated with chest radiation before puberty and those treated in adolescence, they note.

With regard to the clinical characteristics of breast cancer in these women and the outcomes after diagnosis, the authors found that "available limited evidence" suggests that they are similar to those of women in the general population."

The study was funded by the National Cancer Institute. Dr. Oeffinger has disclosed no relevant financial relationships.

Ann Intern Med. 2010;152:444-455.


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