Much research has shown that the hormonal therapy medicine tamoxifen reduces the risk of hormone-receptor-positive cancer coming back (recurrence) and improves the overall survival of women diagnosed with hormone-receptor positive disease.
In the study reviewed here, researchers found that there may be a link between taking tamoxifen for 5 years and a higher risk of developing hormone-receptor-negative cancer in the opposite breast.
Hormone-receptor-negative breast cancer is less common than hormone-receptor-positive breast cancer. About 20% of breast cancers are hormone-receptor-negative. Hormone-receptor-negative breast cancer that also is HER2-negative is called "triple-negative" breast cancer and is considered more aggressive and harder to treat than hormone-receptor-positive breast cancer.
While these results are troubling, the researchers were quick to point out that the findings don't change tamoxifen's risk-benefit ratio. It's also worth noting that the study looked at the medical records of more than 1,000 women in four counties in Washington state. While the study looked at a large number of women, it was geographically limited to only one state. It's possible that something in the environment in the area may have been a factor in the results. More research is needed to confirm the link between taking tamoxifen for 5 years and a higher risk of developing hormone-receptor-negative cancer in the opposite breast.
Some of the cancers in this study were diagnosed almost 20 years ago. At that time, tamoxifen was the standard hormonal therapy medicine; aromatase inhibitors were not commonly used. More research also is needed to see if taking tamoxifen for 2 years and then switching to an aromatase inhibitor for 3 years has the same link to a higher risk of hormone-receptor-negative cancer in the opposite breast. The study reviewed here suggests that taking tamoxifen for less than 5 years may not be associated with the same increase in risk of hormone-receptor-negative cancer.
This study only looked at women that had been diagnosed with breast cancer. It's not clear if the possible link between taking tamoxifen for 5 years and a higher risk of hormone-receptor-negative breast cancer would apply to women at higher-than-average risk but who have never been diagnosed who are taking tamoxifen to reduce risk.
Research continues to show that an aromatase inhibitor is the best hormonal therapy medicine to start with after initial breast cancer treatment for post-menopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer. But tamoxifen is still a good choice, depending on your unique situation. For a number of reasons, including side effects and cost, tamoxifen may be a better choice for some women.
When you're deciding on a treatment plan, keep two things in mind:
If you're being treated for hormone-receptor-positive breast cancer, talk to your doctor about the risks and benefits of tamoxifen and aromatase inhibitors. If you're currently taking tamoxifen, ask whether switching to an aromatase inhibitor makes sense for you. Together, you and your doctor can decide on a treatment plan that's the best one for you.
Breast cancer survivors who take tamoxifen for secondary prevention may actually increase their risk of the more difficult to treat estrogen receptor-negative cancers, according to a population-based study.
Women who took the drug for at least five years had a 4.4-fold higher risk of estrogen receptor-negative contralateral breast cancer (95% confidence interval 1.03 to 19.0) than women not treated with the hormone therapy, according to a study reported in the Sept. 1 issue of Cancer Research.
But these findings don't negate the benefits of tamoxifen or substantially change the risk-benefit ratio, Christopher I. Li, MD, PhD, MPH, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues cautioned.
In their study, a full five-year course of tamoxifen lowered estrogen receptor-positive contralateral breast cancer risk by 60% (95% CI 30% to 70%). Other research has shown lower recurrence and mortality with the drug.
"Nevertheless, risk of a hormone receptor–negative contralateral breast cancer may now need to be tallied among the risks of treatment with tamoxifen, and further studies are needed to determine if other hormonal therapies and the increasingly used aromatase inhibitors in particular also carry this risk," Li's group wrote.
Li speculated that hormonal therapy may give estrogen receptor-negative cancer cells a competitive advantage, reflecting a true increase in risk rather than a shift in the proportion of second cancers that do or do not overexpress estrogen.
If this were the case, any secondary prevention strategy of tamoxifen or aromatase inhibitors as monotherapy or in sequence would confer similar risk, he suggested.
Risk of hormone nonresponsive disease "is of particular clinical concern given the substantially poorer prognosis associated with these tumors compared with ER+ disease," they added, noting that tumors without estrogen or progesterone receptors are 2.3 times more fatal than those with both receptors.
In the study, Li's group looked at a population-based, nested, case-control cohort of 367 women diagnosed with both first primary estrogen receptor–positive invasive breast cancer and second primary contralateral breast cancer along with 728 matched controls diagnosed with only a first breast cancer.
Overall, the breast cancer survivors who had ever taken any type of adjuvant hormonal therapy were at reduced risk of a second primary contralateral breast cancer (odds ratio 0.6, 95% CI 0.5 to 0.8).
This association was found only among women who used hormonal therapy for at least one year and only for hormone receptor–positive contralateral tumors.
Use for at least five years reduced risk of both estrogen receptor-positive contralateral tumors (OR 0.4, 95% CI 0.2 to 0.6) and estrogen- and progesterone-positive tumors (OR 0.4, 95% CI 0.2 to 0.7).
For estrogen receptor-negative and estrogen- and progesterone-negative contralateral tumors, the overall risks did not vary with hormonal therapy but use for at least five years was associated with substantial excess risk of both (OR 3.8, 95% CI 1.0 to 14.6, and OR 4.9, 95% CI 1.1 to 22.5).
Because the study included first breast cancers diagnosed as far back as 1990, most women received adjuvant hormonal therapy in the era when tamoxifen was the standard of care.
Too few took aromatase inhibitors alone or in combination with tamoxifen to analyze separately.
Analyses restricted to tamoxifen showed associations largely identical to the overall results.
The reason for the apparent threshold effect with five years of exposure could be that "a certain length of exposure is needed to foster an environment that promotes estrogen receptor-negative tumor growth," the researchers wrote.
"Alternatively, it could simply be that our study lacked sufficient statistical power to adequately address a dose-response relationship for the relatively rare outcome of an estrogen receptor-negative second primary contralateral tumor," they cautioned.
Another potential limitation of the study, according to the authors, was recall bias of events as much as 15 years earlier.
The study was supported by a grant from the National Cancer Institute.
The researchers reported no conflicts of interest.
Primary source: Cancer Research Source reference: Li CI, et al "Adjuvant hormonal therapy for breast cancer and risk of hormone receptor–specific subtypes of contralateral breast cancer" Cancer Res 2009; 69: 6865-70.
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