The study reviewed here shows that a new osteoporosis medicine, Oporia (chemical name: lasofoxifene), may reduce the risk of breast cancer, especially hormone-receptor-positive breast cancer. The results were presented at the 2008 San Antonio Breast Cancer Symposium.
Lasofoxifene is a SERM (selective estrogen receptor modulator), a type of hormonal therapy medicine. Because of the way they work in the body, SERMs can both improve bone health AND lower the risk of hormone-receptor-positive breast cancer. SERMs block the action of estrogen in breast cells 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, SERMs affect estrogen receptors the way estrogen does, so SERMs strengthen bones. In breast cells, SERMs block the receptors from interacting with estrogen, so breast cancer cells that rely on estrogen can't grow. Hormone-receptor-negative breast cancers don't have estrogen receptors, so aren't affected by SERMs.
Tamoxifen and Evista (chemical name: raloxifene) are other SERMs that many women take to lower breast cancer risk. Both tamoxifen and Evista also improve bone health. Doctors prescribe tamoxifen to lower breast cancer risk in women at high risk and to lower the risk of hormone-receptor-positive breast cancer coming back. Doctors prescribe Evista to post-menopausal women with osteoporosis to improve bone health and lower breast cancer risk. Evista also is prescribed to lower breast cancer risk in post-menopausal women who don't have osteoporosis.
More than 8,500 post-menopausal women participated in the Postmenopausal Evaluation and Risk-reduction with Lasofoxifene (PEARL) study. Half the women got lasofoxifene every day for 5 years. The other half got a placebo (sugar pill). All of the women also took vitamin D and calcium supplements, which can help maintain or improve bone health. The results showed lasofoxifene improved bone health and reduced breast cancer risk, compared to the placebo.
The findings from this study suggest that lasofoxifene may work better than either tamoxifen or Evista to reduce breast cancer risk in post-menopausal women being treated for osteoporosis. During 5 years of treatment, only 0.1% of the women who took lasofoxifene were diagnosed with breast cancer, compared to 0.8% of the women who took the placebo pill. This means that lasofoxifene reduced breast cancer risk by 85%. In comparison, other research has found that tamoxifen reduces breast cancer risk by 43% and that Evista reduces breast cancer risk by 72%, compared to placebo.
The U.S. Food and Drug Administration (FDA) is deciding whether lasofoxifene should be approved to treat osteoporosis and lower breast cancer risk in post-menopausal women.
If you're a post-menopausal woman and have osteoporosis or are taking steps to reduce your risk of developing osteoporosis, you and your doctor will probably consider a number of treatment options to improve your bone health. SERMs, such as Evista and lasofoxifene (which isn't available yet), are one choice. Bisphosphonates are another group of medicines used to strengthen bones. Bisphosphonates include:
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 SERMs and bisphosphonates may cause side effects.
The SERM Evista's side effects may include:
A blood clot or stroke as a side effect of Evista may be serious and life-threatening.
Side effects of bisphosphonates may include:
Some of these side effects can be serious, but the risk of life-threatening side effects is lower 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. Whatever your choice, also ask your doctor about whether vitamin D and calcium supplements should be a part of your overall plan to improve your bone health.
SAN ANTONIO, Dec. 11 (MedPage Today) -- For postmenopausal women, the investigational osteoporosis agent lasofoxifene (Oporia) may substantially reduce the occurrence of hormone-responsive breast cancer, researchers found.
After five years of a randomized trial, estrogen receptor-positive breast cancer occurrence dropped to 0.1% with 0.5 mg/day of lasofoxifene compared with 0.8% among placebo-treated women (P<0.001), Andrea Z. LaCroix, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues reported here.
The significant 85% reduction in relative risk compared with reported reductions of 43% with tamoxifen and 72% with raloxifene (Evista), the researchers reported at the San Antonio Breast Cancer Symposium.
These randomized trial findings for the novel selective estrogen receptor modulator (SERM) may put it back in the running as a competitor for raloxifene.
Raloxifene is the only SERM approved for treatment of osteoporosis and reduction of invasive breast cancer risk in postmenopausal women receiving it for osteoporosis.
Lasofoxifene had also been shown to reduce fracture risk in treatment of osteoporosis, but it was turned down by the FDA in 2005. The drug is now back before the FDA and an advisory board recommended approval, Dr. LaCroix said.
The five-year results were from the international Postmenopausal Evaluation and Risk-reduction with Lasofoxifene (PEARL) study, which included both the three-year randomized controlled results and a two-year extension.
In the trial, 8,556 women ages 50 to 80 with osteoporosis were randomized to placebo or lasofoxifene at a dose of 0.25 or 0.5 mg. All received 400 to 800 IU of vitamin D3 and 1 g of calcium daily as well.
At five years, the higher dose of lasofoxifene reduced estrogen receptor-positive breast cancer occurrence by 81% compared with placebo, although event numbers were low in all arms, Dr. LaCroix said.
Rates were 0.8% with placebo compared with 0.4% with 0.25 mg and 0.1% with 0.5 mg lasofoxifene (hazard ratio 0.52, P=0.073, and HR 0.19, P<0.001).
Cumulative incidence curves started to diverge at two years in the higher dose group and at four years in the lower dose group compared with placebo.
Women at higher risk of breast cancer with Gail scores of 1.66% or higher through five years also had a significant benefit with the higher dose of the investigational SERM (HR 0.25, P=0.022).
When stratified by estradiol levels, estrogen receptor-positive breast cancer rates were reduced most substantially in the groups with higher levels.
For all breast cancer types, the 0.5 mg dose of lasofoxifene also significantly reduced risk 79% compared with placebo (rate 0.2% versus 0.9%, HR 0.21, P<0.001).
Breast biopsy was down 35% with the higher dose (P=0.014) but not with the lower dose compared with placebo (P=1.00).
The study also showed a significant reduction of the coprimary endpoint of nonvertebral fractures at five years, Dr. LaCroix noted, although she did not present the data.
The main adverse event risk with lasofoxifene is an about two-fold increased risk of venous thromboembolism, she said.
Her group concluded that the agent "appears to have a favorable benefit-risk profile for prevention of clinical fractures in postmenopausal women with osteoporosis."
Dr. LaCroix reported being on the scientific advisory committee for Pfizer, Proctor & Gamble, and sanofi-aventis. Her colleagues reported conflicts of interest for Pfizer, Eli Lilly, Schering, Amgen, GlaxoSmithKline, Merck, Novartis, Nycomed, Proctor & Gamble, Servier, Wyeth, AstraZeneca, and Roche. Several authors were employees of Pfizer.
The study was funded by Pfizer.
Primary source: San Antonio Breast Cancer Symposium Source reference: LaCroix AZ, et al "Effects of 5 years of treatment with lasofoxifene on incidence of breast cancer in older women" SABCS 2008; Abstract 11.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
Learn more about our commitment to your privacy
© 2009 Breastcancer.org - All rights reserved.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
_tcm8-332386.jpg "wellness_dvd_promo")