Raloxifene Lowers Risk of Breast Cancer by 72% - Brief Article

0 Comments | Family Practice News, Feb 1, 2001 | by Bruce Jancin

At 4 -year follow-up, benefit was greatest with higher lifetime estrogen exposure.

SAN ANTONIO -- Among women taking raloxifene, those with the highest lifetime exposure to estrogen had the greatest reduction in breast cancer risk.

That was a key finding of an analysis of new data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial reported at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

The latest follow-up data from the MORE trial show that 4 years of raloxifene therapy reduced the risk of all breast cancers by 72%, compared with placebo. The selective estrogen receptor modifier (SERM) reduced the risk of estrogen receptor-positive breast cancers by 84%, said Dr. Marc E. Lippman, professor of medicine at Georgetown University, Washington.

A particularly encouraging new finding was that the higher a woman's lifetime exposure to estrogen--hence, the greater her breast cancer risk--the more potent her breast cancer risk reduction appeared to be with raloxifene, which is indicated for the prevention of osteoporosis in postmenopausal women, Dr. Lippman added.

MORE was a randomized double-blind trial comparing raloxifene with placebo in 7,705 post-menopausal women with osteoporosis. The primary study end point was prevention of fractures, for which raloxifene proved effective and now has Food and Drug Administration approval. A secondary end point was the incidence of breast cancer.

With a total of 79 breast cancers at the 4-year mark, the rate was 4.7 cases per 1,000 patient-years in the placebo group, compared with 1.3 with raloxifene, a highly significant difference. This protective effect was essentially restricted to cancers that were estrogen receptor positive. There were 31 cases of estrogen receptor-positive breast cancer with placebo but only 10 with raloxifene, even though the raloxifene treatment arm was twice the size of the placebo group.

Increased exposure to estrogen has been linked to greater breast cancer risk in hundreds of studies. The MORE researchers sought to determine whether raloxifene's cancer-preventing effects were greater in women with high lifetime estrogen exposure, based on surrogate markers for such exposure in the osteoporotic study population.

This indeed proved to be the case. For example, greater bone mineral density is known to be a surrogate marker for greater lifetime estrogen exposure. Among MORE participants in the placebo group whose femoral neck bone mineral density was in the highest one-third of the study population, the 4-year incidence of breast cancer was significantly greater than in the lowest two-thirds. Similarly, women in the top one-third in terms of baseline serum estradiol-with a value of at least 5 pmol/ L--had a breast cancer rate 2.5-fold greater than in those with lesser estradiol values.

Raloxifene protected against breast cancer in women having surrogate markers indicative of low lifetime estrogen exposure, but reduced risk by an even greater margin in those with high lifetime estrogen exposure. For example, breast cancer risk in women in the lower two-thirds in terms of bone mineral density was lowered by 56% with raloxifene, compared with placebo--but by 94% in those in the highest bone mineral density tertile.

Similarly, raloxifene was associated with a greater reduction in breast cancer risk in women who were in the top one-third for baseline serum estradiol or body mass index than in women who were in the lower two-thirds. Minor trends toward greater protection against breast cancer also were seen among women with later onset of menopause or a history of HRT.

In terms of side effects, 4 years of raloxifene use was associated with a 2.8-fold increased relative risk of deep venous thrombosis and a 2.8-fold elevated rate of pulmonary embolus, compared with placebo. These increases are comparable to those noted for tamoxifen, another SERM, in other trials. Raloxifene wasn't associated with any increase in endometrial cancer in MORE, according to Dr. Lippman.

Asked if he believes the new MORE data give a green light to prescribing raloxifene to prevent breast cancer, the oncologist replied with an emphatic "No."

"My personal belief is tamoxifen is the drug of choice, as it's the only approved drug for breast cancer prevention," he said. In his practice, he reserves raloxifene for breast cancer risk reduction in the few women who can't tolerate tamoxifen.

Now underway is the Study of Tamoxifen and Raloxifene (STAR), a head-to-head comparison of the two SERMs in the arena of breast cancer prevention.