Tamoxifen is a hormonal therapy medicine that can be taken by women with a much higher-than-average risk of breast cancer to reduce risk. The study reviewed here found that tamoxifen was successful at reducing risk only in high-risk women whose breast density significantly decreased during the first year or so of taking tamoxifen. The results were presented at the 2008 San Antonio Breast Cancer Symposium.
More than 7,000 women at high risk for breast cancer, but who had never been diagnosed, participated in the study, called IBIS-1. About half the women took tamoxifen for 5 years. The other half of the women took a placebo (sugar pill) for 5 years. After about 8 years of follow-up, the women who took tamoxifen were 27% less likely to develop breast cancer compared to the women who took the placebo.
During the study, the researchers measured the breast density of the women who took tamoxifen. Breast density is the proportion of fatty tissue compared to non-fatty tissue in the breast. A denser breast has more non-fatty tissue in it than a less-dense breast. Breasts usually get a little less dense over time.
More than 45% of the women who took tamoxifen had their breast density drop by 10% or more during the first 12 to 18 months of taking tamoxifen. The other 54% of these women had their breast density drop by less than 10% during the same time period. The researchers compared the breast cancer risk of the two groups of women who took tamoxifen to women who took the placebo.
The results:
This means that women who took tamoxifen and didn't have a 10% or greater drop in breast density within the first year or so on tamoxifen had no reduction in breast cancer risk. Essentially, the tamoxifen wasn't effective for these women.
Tamoxifen may cause bothersome and sometimes serious side effects, including hot flashes and life-threatening blood clots. Many women who might benefit from taking tamoxifen to lower breast cancer risk choose not to take tamoxifen because they're worried about these side effects, as well as whether tamoxifen actually will reduce breast cancer risk.
In a perfect world, tamoxifen would only be given to high-risk women whose breast cancer risk would be reduced significantly. This study may offer a way to figure out if a woman at high risk for breast cancer is getting protective benefits from taking tamoxifen. The study suggests that only women whose breast density drops by 10% or more after 12 to 18 months of taking tamoxifen will benefit from 5 years of tamoxifen. Still, these results are EARLY results. More research is needed before lower breast density can be used to measure the effectiveness of tamoxifen.
If you have a higher-than-average risk of breast cancer and you're taking (or thinking about taking) tamoxifen, you might want to ask your doctor about this study. Together you can decide if and for how long tamoxifen treatment makes sense for you.
Visit the Breastcancer.org Protective Measures for Women at High Risk page to learn more about ways to lower breast cancer risk if your risk is considered to be higher than average.
SAN ANTONIO, Dec. 15 (MedPage Today) -- Tamoxifen's likely efficacy in preventing breast cancer may be predicted by changes in tissue density on annual mammography scans, researchers found.
High-risk women in the randomized controlled IBIS-1 trial who had at least a 10% reduction in mammographic breast density over the first 12 to 18 months of tamoxifen prophylaxis had a 63% reduction in breast cancer risk (P=0.002) whereas other women had no benefit (P=0.89).
The benefit was even greater for women with precancerous atypical hyperplasia or lobular carcinoma in situ lesions, Jack Cuzick, Ph.D., of the Cancer Research United Kingdom Center for Epidemiology, Mathematics, and Statistics in London, and colleagues reported at the San Antonio Breast Cancer Symposium here.
If validated, breast density changes would be the first biomarker that could be used by clinicians to determine who stands to benefit from continued tamoxifen prophylaxis, Dr. Cuzick said.
"If your preventive strategy doesn't work, then there's no reason in pressing on for five years," he said.
Conversely, this information could be used to reassure women that the drug is having a benefit, commented Powel H. Brown, M.D., Ph.D., of Baylor College of Medicine in Houston, who moderated the press conference at which the findings were reported.
Currently only about one in 10 candidates accept prophylactic tamoxifen, often because of concern about toxicity, such as blood clots, he said.
This kind of test for efficacy could change women's assessment of the risk-benefit ratio and potentially improve long-term adherence or even willingness to go on the drug, Dr. Brown noted.
Many prior studies have documented mammographic breast density as the greatest contributor to breast cancer risk among known risk factors, predicting four- to five-fold higher risk of breast cancer.
To see what potential it had as a biomarker, Dr. Cuzick's group analyzed findings from the IBIS-1 study, which included 7,154 high-risk women randomized to tamoxifen or placebo for five years.
After about eight years of follow-up, there was an overall 27% reduction in breast cancer risk with tamoxifen compared with placebo (142 versus 195 cases, P=0.004).
While mammographic density declined over time, likely because of aging, in both groups, the reduction was significantly greater in the tamoxifen-treated group (from 41.92% to 28.2% versus from 42.59% to 36.3% with placebo).
The majority of the breast density reduction occurred over the first 18 months of treatment. The 46% of patients who had at least a 10% reduction over this period had a significantly higher benefit from tamoxifen in reducing breast cancer whereas others did not (OR 0.37 versus OR 1.03, P=0.004 between density groups).
This effect was similar across age groups and different baseline breast densities.
A drop in breast density with tamoxifen was particularly predictive of benefit among the high-risk group with atypical hyperplasia or lobular carcinoma in situ (OR 0.29, 95% confidence interval 0.04 to 2.01), although not significantly more so than in other women (P=0.82).
Although breast density is routinely included on radiology reports from annual screening mammograms, "at the moment that information is not used," he said.
Other studies have shown that breast density begins to return to baseline after women discontinue tamoxifen, Dr. Cuzick noted.
An important remaining question is whether the breast density effect is only for tamoxifen or could predict efficacy of other preventive strategies, such as raloxifene (Evista), Dr. Cuzick said.
He also cautioned that the findings could not address whether breast density changes predict effectiveness of tamoxifen or other agents among women who have already developed breast cancer.
The IBIS-I trial was supported in part by Cancer Research UK and, in Australia, by the National Health and Medical Research Council. Dr. Cuzick reported having had conflicts of interest for AstraZeneca, Novartis, Pfizer, and Lilly.
Dr. Brown reported receiving research funding from Lilly.
Primary source: San Antonio Breast Cancer Symposium Source reference: Cuzick J, et al "Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1" SABCS 2008; Abstract 61.
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