Raloxifene (Evista) Reduces Risk of ER-Positive Invasive Breast Cancer
SAN FRANCISCO, June 11 -- Treatment with raloxifene (Evista) reduced the risk of receptor-positive invasive breast cancer by more than half among women enrolled in a randomized study of heart disease prevention.
Patients randomized to the selective estrogen receptor modulator had 55% fewer invasive estrogen receptor-positive breast cancers than women in the placebo group, Deborah Grady, M.D., of the University of California San Francisco, and colleagues reported in the June 18 issue of the Journal of the National Cancer Institute.
The reduction in receptor-positive disease accounted for virtually all of the 44% overall reduction in invasive breast cancer previously reported from the study.
Neither invasive receptor-negative breast cancer nor noninvasive breast cancer was reduced by raloxifene treatment.
The findings also are consistent with those from a trial of raloxifene to prevent osteoporotic fractures in postmenopausal women.
"Raloxifene appeared to be most effective in reducing the incidence of breast cancer during the first four years of treatment," the authors said. "Moreover, the effect of treatment appeared to be similar across subgroups defined by age, reproductive history, and breast cancer risk status."
The findings came from the Raloxifene Use for the Heart (RUTH) trial, which involved 10,101 women with coronary heart disease or who were at high risk for CHD.
The primary results of the trial showed no effect of raloxifene on heart disease risk, but 44% overall reduction in the risk of invasive breast cancer.
The findings followed those from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, which involved 7,705 postmenopausal women with osteoporosis. Among women treated for four years, raloxifene reduced the risk of invasive breast cancer by 72% compared with placebo.
In the current study, Dr. Grady and colleagues analyzed the RUTH data to determine the effects of raloxifene on breast cancer by histologic type, tumor stage, lymph node status, and tumor grade and size.
The original findings from RUTH included a 44% reduction in the hazard ratio for invasive breast cancer in women treated with raloxifene. The reduction translated into the prevention of 1.2 invasive breast cancers per 1,000 women treated for one year.
Dr. Grady and co-authors found that the overall reduction in the risk of invasive breast cancer reflected a hazard ratio of 0.45 (95% CI 0.28 to 0.72) in the subgroup of women with hormone receptor-positive tumors.
The magnitude of the overall reduction in the risk of invasive breast cancer was similar across subgroups defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and five-year estimated risk of invasive breast cancer.
Raloxifene was associated with an increased risk of venous thromboembolism and fatal stroke in RUTH.
Assuming that the relative risks of the trial apply to women in the general population, the authors suggested the best risk:benefit ratio would occur in women with a high risk of breast cancer and osteoporosis and a low risk of venous thromboembolism and stroke.
They also pointed out that participants in the RUTH trial were selected because they either had known coronary disease or were at high risk for coronary disease.
"Thus, it is possible," they wrote, "that the ?ndings of the RUTH trial may not be able to be generalized to women who are not at high risk for coronary disease."
| Dr. Grady acknowledged receiving salary support for research from Eli Lilly. |
Primary source: Journal of the National Cancer Institute Source reference: Grady D, et al "Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk" J Natl Cancer Inst 2008; 100: 854-861.
What breastcancer.org says about this article…
Raloxifene (Evista) Reduces Risk of ER-Positive Invasive Breast Cancer
Evista (chemical name: raloxifene) is a hormonal therapy medicine used to strengthen bones in women with osteoporosis. In September 2007, the U.S. Food and Drug Administration approved using Evista to reduce the risk of breast cancer in post-menopausal women at high risk. Evista also is approved to reduce breast cancer risk in post-menopausal women with osteoporosis.
The study reviewed here, the RUTH (Raloxifene Use for The Heart) study, provides more information on Evista and breast cancer risk reduction in post-menopausal women:
- Post-menopausal women taking Evista were 44% less likely to develop invasive breast cancer than women not taking Evista.
Evista was much more likely to reduce the risk of breast cancers that are hormone-receptor-positive:
- Evista lowered the risk of hormone-receptor-positive invasive breast cancer risk by 55%.
Evista was less likely to reduce the risk of hormone-receptor-negative cancers. More than half of all breast cancers are hormone-receptor-positive.
This study followed more than 10,000 post-menopausal women who either had coronary artery disease or were at high risk for it. The researchers wanted to know if Evista would lower the risk of future heart disease in the women. The researchers also kept track of how many women were diagnosed with invasive breast cancer during the study.
About half the women got Evista and the other half got a placebo. About half of the women were followed for more than 5 1/2 years. The women taking Evista had a lower risk of breast cancer, but Evista didn't lower the risk of heart disease. Evista lowered breast cancer risk most during the first 4 years of treatment. Breast cancer risk was lowered regardless of other factors that can influence risk, such as age, being overweight, family history, and hormone replacement therapy (HRT) use.
It's important to note that only women who already had coronary artery disease or were at high risk for it participated in this study. So the researchers can't say if the results would be the same if women without heart disease or a high risk for it were involved. Still, it's likely that the results would be similar.
Another study, called MORE (Multiple Outcomes of Raloxifene Evaluation), found that Evista reduced the risk of invasive breast cancer by 72% in post-menopausal women. The MORE study included women who didn't have heart disease or a higher risk of heart disease.
Evista is a SERM (selective estrogen receptor modulator) hormonal therapy. SERMs block the action of estrogen in breast and certain other cells by sitting in the cells' estrogen receptors. SERMs don't affect all estrogen receptors the same way because they're selective (as the name says). In bone cells, Evista interacts with the receptors like estrogen does and strengthens bones. In breast cells, Evista blocks the receptors' interaction with natural estrogen, which reduces estrogen's ability to make cells grow. This is probably why Evista lowers the risk of hormone-receptor-positive breast cancers. Hormone-receptor-negative breast cancers don't have estrogen receptors, so wouldn't be affected by Evista.
Tamoxifen is also a SERM. Tamoxifen is used to lower breast cancer risk in women at high risk and to lower the risk of hormone-receptor-positive breast cancer coming back. Tamoxifen also can improve bone health.
If you're a post-menopausal woman thinking about taking medicine to strengthen your bones, Evista, which is a pill taken by mouth, is one choice you and your doctor can consider. Evista also can reduce your risk of invasive breast cancer. Bisphosphonates are another group of medicines used to strengthen bones. The bisphosphonates include:
- Actonel (chemical name: risedronate)
- Boniva (chemical name: ibandronate)
- Fosamax (chemical name: alendronate)
- Reclast (chemical name: zoledronic acid)
Reclast is given intravenously once a year. The others are pills taken by mouth.
Bisphosphonates strengthen bones better than SERMs, but none of the bisphosphonates have been shown to lower the risk of breast cancer in women who've never been diagnosed.
Both Evista and the bisphosphonates may cause side effects. Evista's side effects may include:
- hot flashes
- sweating
- joint pain
- leg cramps
- flu-like symptoms
- blood clots deep in the legs
- a blood clot that travels to the lungs (called a pulmonary embolism)
- stroke
If a woman does develop a blood clot or has a stroke as a side effect of Evista, it may be serious and life-threatening. Some women in the RUTH study experienced these serious side effects.
Side effects of bisphosphonates may include:
- upset stomach
- muscle and joint pain
- esophagus irritation
- osteonecrosis of the jaw (in rare cases)
Some of these side effects can be serious, but the risk of life-threatening side effects is less with bisphosphonates than with Evista.
You and your doctor will need to weigh the risks and benefits of each treatment. You'll also need to consider your unique situation. Do you have a higher than average risk of breast cancer? If so, then Evista may be a good choice for you. Do you have a higher than average risk of breaking a bone? If so, you may opt for the added bone-strengthening ability of a bisphosphonate. Together, you and your doctor can decide what makes the best sense for YOU.