Tamoxifen Shows Major Benefit, Some Risk

The results of the national Breast Cancer Prevention Trial (BCPT) are in, and the news is great for women.

 

Tamoxifen (Nolvadex®), which has been used to treat breast cancer for the past two decades, was shown to be effective in preventing the disease among high-risk women, reducing the incidence by 45 percent.

 

While tamoxifen has not been proven to eliminate cancer risk, its ability to reduce the chance of the disease developing complements well-documented early detection strategies including mammography, says Dr. Scott M. Lippman, professor and chairman of the Department of Clinical Cancer Prevention at M. D. Anderson.

 

Austella Whittington, whose mother and an older sister were diagnosed with breast cancer, was one of more than 13,000 women to participate in the national Breast Cancer Prevention Trial.

 

Study results were released this spring, about 14 months earlier than expected. The more than 13,000 women participants were notified of the findings so those individuals who had been taking the placebo could consider starting tamoxifen therapy after consulting with their personal physicians.

 

M. D. Anderson researchers have played an instrumental role in the National Cancer Institute-funded prevention study, which was launched in 1992 and conducted by the National Surgical Adjuvant Breast and Bowel Project. With more than 300 women volunteering in the tamoxifen trial at the cancer center, M. D. Anderson was the largest center participating in the medical study among the more than 270 sites across the country.

 

"This is truly an historic time in the fight against cancer," says Dr. Lippman, an investigator on the study. "My colleagues and I, as well as the hundreds of women who participated in the trial at M. D. Anderson, are proud to have been associated with this landmark achievement.

 

"For years, M. D. Anderson has been a leader in the sometimes controversial field of prevention in general and chemoprevention in particular," he continues. "We believe that chemoprevention trials under way at M. D. Anderson -- for cancers of the colon, lung, head and neck, bladder and prostate -- will further give credence to the idea that cancer can be prevented."

 

Dr. Lippman is quick to point out that the success of this trial could not have been possible without the "women who made the decision to enroll in the study."

 

Austella Whittington was one of them.

 

With a strong family history of breast cancer -- both her mother and an older sister were diagnosed with the disease -- and the need for minority participation as her motivation, the 46-year-old African-American woman signed up for the trial, hoping to make a difference not only in her life, but also for her nine other sisters and the next generation of women.

 

"After reading a news brief about the trial, I felt it was important to do," says Whittington, who found out that she had been taking tamoxifen. "The more doctors know about the disease and how to prevent it, the better off we'll all be."

 

Whittington thought if she could contribute to that understanding, her involvement will have been worth it. And now with these positive results, she says, "I'm glad I did it and that I could help."

 

In the nationwide study of 13,388 healthy women, those assigned to take tamoxifen developed 85 cases of invasive breast cancer compared to 154 cases in the individuals assigned to the placebo.

 

Tamoxifen did increase the women's chances of three rare, but life-threatening health problems, however. There were 33 cases of endometrial cancer (cancer of the lining of the uterus) in the tamoxifen group versus 14 cases in the placebo group; 17 cases of pulmonary embolism (blood clot in the lung) in the tamoxifen group as opposed to six cases in the placebo group; and 30 cases of deep vein thrombosis (blood clots in major veins) in the tamoxifen group in contrast to 19 cases in the placebo group.

 

Among those individuals at increased risk for breast cancer, women under age 50 didn't appear to experience any excess risk of adverse effects from the use of tamoxifen.

 

About 40 percent of the participants were ages 35-49, 30 percent were ages 50-59 and 30 percent were age 60 or older. All age groups showed similar reductions in breast cancer incidence while taking tamoxifen.

 

In addition, the study results indicated that there were fewer diagnoses of noninvasive breast cancer, such as ductal carcinoma in situ, in the tamoxifen group. During the trial period, eight participants died of breast cancer -- three in the tamoxifen group and five in the placebo group.

 

Women who are at an increased risk of breast cancer now have the option to consider taking tamoxifen to reduce their chances of developing breast cancer. According to Dr. Therese Bevers, medical director of M. D. Anderson's Cancer Prevention Center, the decision to take the drug "will be a personal one. There are significant benefits of tamoxifen, but also some risks. These issues must be discussed on a one-to-one basis between the woman and her health care provider before deciding if tamoxifen is the right choice for her."

 

Dr. Bevers adds that several other factors should be considered, including a woman's own risk of getting breast or endometrial cancer; family history (if a first degree relative -- mother, sister or daughter -- has had breast cancer); personal history of abnormal biopsy results including lobular carcinoma in situ as well as atypical ductal or lobular hyperplasia; chance of developing a vascular event; and anxiety about getting the disease.

 

In addition to examining tamoxifen's preventive effects on breast cancer, the BCPT looked at whether taking the drug could also decrease the number of heart attacks and bone fractures in these women. There wasn't any difference in the number of heart attacks between the tamoxifen and placebo group, but women taking the drug had fewer bone fractures of the hip, wrist and spine.

 

Participants will continue to be followed by a larger trial comparing tamoxifen with the new and related agent raloxifene in post-menopausal women.

 

Got a question about tamoxifen, prevention studies or cancer? Call the Cancer Information Service at 1-800-4-CANCER. If you are interested in enrolling in cancer prevention or treatment studies at M. D. Anderson, call 1-800-392-1611.

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