Women who have had breast cancer are at increased risk for developing other cancers, and this risk cannot be fully explained by treatment history or genetic and environmental influences, new research shows.

The largest study ever to examine new primary cancers among breast cancer survivors included more than half a million women enrolled in 13 cancer registries in Europe, Canada, Australia, and Singapore. The women were followed for an average of about seven years, but some were followed much longer.

Women with a history of breast cancer had a 25 percent increase in the risk of developing new cancers at sites other than the breast, compared with women with no history of the disease. That is in line with increases reported in previous, smaller studies.

“It is important to emphasize that this extra risk is quite moderate, and doctors have known about it for many years,” researcher Lene Mellemkjaer, PhD, tells WebMD.

Second Cancers by Site

The various registries followed more than 525, 000 women treated for breast cancer as early as 1943 and as late as 2000, with 133,414 women followed for more than 10 years after their initial diagnosis, notes a news release.

The younger a woman was when her breast cancer was diagnosed, the higher her risk for developing a second new cancer.

Increased risk was seen in several cancers including lung, colon, stomach, ovary, uterus, leukemia, skin, bone, sarcoma, and pancreas. For example, women one to nine years after breast cancer had between a 50 percent and 60 percent increase in leukemia, nonmelanoma skin cancer, endometrial (uterine) cancer, and thyroid cancer.

Interestingly, decreased risk was noted in multiple myeloma, cervical, liver, and brain cancers.

The study is published in the Dec. 8 online edition of the International Journal of Cancer.

While the findings may sound scary, a breast cancer expert who talked to WebMD pointed out that the risk of developing a second cancer is still very small for breast cancer survivors.

Among women in the study who remained cancer-free for at least 10 years after breast cancer treatment, only three extra cancers were seen annually among 1,000 women.

“That is one-third of a percent, which is pretty small,” says Debbie Saslow, PhD, of the American Cancer Society.

Treatment Risks Lower Today

Saslow points out that the risk for developing treatment-related second cancers is lower today than in the past, thanks to advances in radiation, chemotherapy, and other treatments.

The study found an almost sixfold increase in the risk of cancer in connective tissue of the thorax and upper limbs -- rare cancers believed to be caused by radiation treatment.

“We have gotten much better at targeting radiation to protect the rest of the body while we treat the cancer,” Saslow says.

The excess of endometrial (uterine) cancers seen in the study can be largely traced to the hormonal treatment tamoxifen. But Saslow says doctors are increasingly treating patients with another hormonal therapy that does not increase endometrial cancer risk.

While much of the observed increase in risk could be explained by breast cancer treatment and hereditary or environmental factors, Mellemkjaer and colleagues concluded that other, unidentified factors may also come into play.

“The known effects of treatment and common risk factors do not seem to fully explain the excesses,” they wrote. “Future knowledge about the impact of such factors may add further explanations in addition to potential influences from increased surveillance and general cancer susceptibility.”

Salynn Boyles, reviewed by Louise Chang, MD

SOURCES: Mellemkjaer, L. International Journal of Cancer, Dec. 8, 2005; vol 118: online edition. Lene Mellemkjaer, PhD, senior researcher, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. Debbie Saslow, PhD, director, breast and gynecological cancer, American Cancer Society. News release, International Journal of Cancer.