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Long-term tamoxifen use linked to rise in second breast cancer, study finds

A new study suggests long-term use of tamoxifen is linked to increased risk of developing an aggressive type of breast cancer, but experts say the drug’s proven track record in reducing risk of both recurrence of the disease and death outweigh potential negative effects.

TORONTO — A new study suggests long-term use of tamoxifen is linked to increased risk of developing an aggressive type of breast cancer, but experts say the drug’s proven track record in reducing risk of both recurrence of the disease and death outweigh potential negative effects.

Researchers from Fred Hutchinson Cancer Research Center in Seattle looked at 728 women who had been diagnosed with breast cancer. Those women were compared to 367 others diagnosed with both a first and second breast cancer.

A second breast cancer can mean a tumour occurring in the opposite breast or when two separate tumours develop in the same breast.

The main finding from the study, published online Tuesday in the journal Cancer Research, was that tamoxifen lowered the risk of any second breast cancer overall by about half, said lead author Dr. Christopher Li.

While long-term use of the drug for five or more years reduced the more common type of breast cancer by about 60 per cent, it also increased the risk of a more aggressive subtype of the disease by more than 400 per cent, Li said.

Tamoxifen is an estrogen-blocking drug. Li said such drugs were specifically designed to block the estrogen receptor to prevent the growth of breast cancer cells. But not all breast cancers have the estrogen receptor (ER), Li said. Those that don’t tend to be more aggressive and to spread more quickly.

“For the estrogen receptor-positive cancer, we have targeted therapy that again has been proven to again reduce mortality,” said Li. “That’s one of the reasons why ER-negative cancers are more worrisome because we don’t have a targeted treatment for them.”

Li said it’s important to remember that any treatment has risks and benefits associated with it, and tamoxifen is no exception.

Tamoxifen lowers breast cancer patients’ risk of dying of the disease, and has also been shown to lower a woman’s risk of developing a recurrent breast cancer and a second breast cancer, he noted. But use of tamoxifen also comes with risk of stroke, as well as the risk of endometrial cancer, he added.

“So here we’re finding that we’re adding potentially another risk to the risk-benefit equation,” Li said. “We’re finding that there is this increased risk in this more aggressive subtype of second breast cancer. However, we also overall found using tamoxifen did lower the risk of any type of second breast cancer overall.”

“For that reason, we don’t really think that this study changes the overall risk-benefit equation because the benefits for most women who are eligible to use this treatment are going to still outweigh the risks.”

Dr. Pamela Goodwin, head of the medical breast program at Toronto’s Princess Margaret Hospital, said there is a net benefit in using tamoxifen, with decreased risks of death, recurrence of the disease and cancer spreading to the other breast.