New guidelines help doctors determine which women should be offered tamoxifen to prevent breast cancer (dateline May 18, 1999)
- How do women determine if they are at risk for breast cancer?
- ASCO recommendations are disputed by some
- The role of raloxifene in preventing breast cancer
A new study suggests that women whose breast biopsy shows pre-cancerous cells may benefit from the drug tamoxifen (brand name Nolvadex) to prevent breast cancer. The study also recommends that all women over 60 or women with other factors that place them at high risk for breast cancer maybe candidates for tamoxifen therapy.
In late 1998, tamoxifen became the first drug to be approved for preventing breast cancer, after research showed it reduced the chance of developing breast cancer by 50% in women with at high risk. The October 29, 1998 press release announcing the FDA approval of tamoxifen can be found online at www.nolvadex.com/pr2.cfm. However, doctors have not been sure how to best determine how high a woman's breast cancer risk needed to be before they recommended the drug, since tamoxifen carries its own risks. This study and guidelines from the National Cancer Institute (NCI) can assist doctors in determining which women should be offered tamoxifen.
The new tamoxifen recommendations were issued by the American Society of Clinical Oncology (www.ASCO.org) at its annual meeting in Atlanta. The study suggests that millions of healthy women could benefit from tamoxifen. The new research further suggests that the drug may also benefit women who have abnormal cells that may or may not develop into cancer. These abnormalities are lobular carcinoma in-situ (LCIS) or atypical hyperplasia (AH). LCIS and AH have long been considered a signal that a woman may develop breast cancer, said Dr. Donald Wickerham of Boston Medical Center. "But other than to schedule regular mammograms and watch closely for cancerous changes, we were unsure what to do."
The study analyzed 13,388 breast cancer patients given either tamoxifen or placebo (an inactive substance given as if it were a real drug). In the subset of more than 2,000 women with LCIS or AH, those who took tamoxifen were 66% to 86% less likely to develop breast cancer within five years, compared with those who took the placebo. Typically, women with either condition are at a six percent increased risk of developing breast cancer within five years, he said.
The ASCO recommendations provide further guidance for women at high risk due to factors other than suspicious cellular changes (shown on biopsy). Based on an analysis of existing scientific literature, the ASCO guidelines say that women aged 35 or older with at least a 1.66% risk of getting breast cancer over the next five years should be offered tamoxifen (see below for summarized conclusions to the report). Age itself places a woman at risk, with almost 20 million women over 60 falling into this category.
An array of factors, from family history and race to age at first menstruation and number of children are used to determine if a woman is at high risk of breast cancer and merits the recommendation of tamoxifen. Answers to the following questions can help a woman and her doctor determine her risk:
- Did you have your first period before age 12?
- Did you have your first child after age 30?
- Are you childless?
- Did/does your mother have breast cancer?
- Do you have any sisters who have had or have breast cancer?
- Do you have any daughters who have had or have breast cancer?
- Have you ever had a breast biopsy?
- Did the doctor ever tell you that one of your biopsies showed a premalignant or precancerous condition?
- Did the doctor ever tell you that one of your biopsies showed early cancer that has not spread yet?
The National Cancer Institute (NCI) has developed a software program called the Breast Cancer Gail Model Risk Assessment Tool to help women and their doctors calculate their risk of breast cancer. The formal Breast Cancer Gail Model Risk Assessment Tool incorporates statistical methods that were utilized by the National Surgical Adjuvant Breast and Bowel Project to screen patients for the groundbreaking Breast Cancer Prevention Trial. This tool is available as a slide rule or computer software package but is intended for physician use only. However, a version of this software has been prepared for public use and is available online at www.nolvadex.com/prescreen.cfm
Not everyone agreed with the ASCO's study and recommendation, pointing out that tamoxifen carries its own risks. Tamoxifen increases the chance of developing cancer of the uterine lining, potentially fatal blood clots in the legs and cataracts. "We are not saying that all of these women should take it, just that it should be offered," countered panel moderator Dr. Lori Goldstein of the Fox Chase Cancer Center in Philadelphia. "What we are saying is that these patients should be closely monitored, with regular breast exams and a discussion of tamoxifen's risks and benefits."
Recent research has suggested that a drug known as raloxifene (brand name Evista) used to treat osteoporosis, may offer a safer alternative to tamoxifen. Raloxifene is a related drug to tamoxifen. However, ASCO said that there is not enough evidence to support a recommendation for use of raloxifene in breast cancer prevention (more details can be found in the full ASCO report).
A study of data on more than 7,500 women who took raloxifene or placebo to treat osteoporosis showed that the risk of breast cancer was two-thirds lower in those who received raloxifene. But the study only followed women for 40 months (3.3 years). A longer-term follow-up is need before a recommendation can be made. Click here for information about the new STAR trial to study and compare the effects of raloxifene and tamoxifen on the prevention of breast cancer.
"American Society of Clinical Oncology Technology Assessment on Breast Cancer Risk Reduction Strategies: Tamoxifen and Raloxifene"
"Conclusions: For women with a defined 5-year projected risk of breast cancer of 1.66%, tamoxifen (at 20 mg/d for up to 5 years) may be offered to reduce their risk. [At a 1.66% risk, the benefits of tamoxifen begin to outweigh the potential risks]. It is premature to recommend raloxifene use to lower the risk of developing breast cancer outside of a clinical trial setting. On the basis of available information, use of raloxifene should currently be reserved for its approved indication to prevent bone loss in postmenopausal women. Conclusions are based on single-agent use of the drugs. At the present time, the effect of using tamoxifen or raloxifene with other medications (such as hormone replacement therapy), or using tamoxifen and raloxifene in combination or sequentially, has not been studied adequately. The continuing use of placebo-controlled trials in other risk-reduction trials highlights the current unanswered issues concerning the use of such interventions, especially when the influence on net health benefit remains to be determined. Breast cancer risk reduction is a rapidly evolving area. This technology assessment represents an ongoing process with existing plans to monitor and review data and to update recommendations in a timely matter."
- The full ASCO study may be found online at http://www.asco.org/prof/pp/html/guide/brisk/m_briskintro2.htm
- The American Society of Clinical Oncology (ASCO) maintains an excellent website for members, physicians and the public at www.ASCO.org.
- The story "Breast cancer pill could benefit millions of women: Doctors outline who should be offered tamoxifen" by Charlene Laino was referenced in the preparation of this summary and may be found online at www.msnbc.com/news/270812.asp
- Zeneca Pharmaceuticals maintains a website about tamoxifen (product name Novaldex) at www.nolvadex.com
- Visit the Susan G. Komen Cancer Foundation/Breast Help website at www.breastcancerinfo.com/bhealth/html/tamoxifen.asp to learn more about using tamoxifen to treat breast cancer.
- The American Cancer Society provides information on tamoxifen and raloxifene www.cancer.org