Oncologists Should Work Like Cardiologists, Researchers Say

Allison Gandey

December 18, 2006

December 18, 2006 (San Antonio) — Cancer doctors are too focused on treatment and don't spend enough time on prevention, delegates at the San Antonio Breast Cancer Symposium were told. "Cancer in general and breast cancer in particular is preventable," Leslie Ford, MD, from the National Cancer Institute, in Bethesda, Maryland, said during her talk on recent advances. "We have to start thinking like cardiologists," she told colleagues attending the meeting.


A beneficial preventive intervention maximizes benefit while minimizing risk in high-risk patients — something cardiologists have excelled at, Dr. Ford said. She argues that the effectiveness of current breast cancer prevention is comparable to widely accepted cardiovascular prevention studies, and she presented a comparison of numbers needed to treat in recent breast cancer trials with those of lipid-lowering trials.

Illustration of Numbers Needed to Treat
Indication
Population
Intervention
Outcome
Number Needed to Treat
Breast cancer
Adjuvant tamoxifen
High-risk
Tamoxifen vs none
Tamoxifen vs raloxifene
Recurrence
Invasive breast cancer
8
55
Lipid lowering
Post-CHD cholesterol

Primary-prevention cholesterol
Normal/low HDL cholesterol
Simvastatin vs. placebo
Pravastatin vs placebo
Lovastatin vs placebo
Second coronary event
Coronary event

Coronary event
12
44
49

"I agree with Dr. Ford that we need to focus our efforts in new ways and seek a different perspective," session comoderator Mamta Kalidas, MD, from the Baylor College of Medicine, in Houston, Texas, told Medscape. "We do need to focus more on prevention. In cardiology, you can measure cholesterol levels and blood pressure, but with breast cancer, we're still trying to identify what we can use as markers of prevention, which has been a challenge to date."

Dr. Kalidas also pointed to some key differences between oncology and cardiology trials, which have made developing prevention strategies difficult. "It takes thousands of women and years and years of follow-up to get data to verify whether agents work for prevention. To see the end results of our trials can take a lot longer than the end results of many cardiology trials."

Tamoxifen and Raloxifene Proposed as Key Prevention Agents in Breast Cancer

Dr. Ford told the meeting that the proof of principle that breast cancer can be prevented in high-risk women was established by the Breast Cancer Prevention Trial with tamoxifen. Published in 1998, investigators showed a 49% reduction in invasive breast cancer in women assigned to tamoxifen vs placebo. A subsequent report published in 2005 of the seven-year follow-up of the work confirmed this result as well as the side effects associated with tamoxifen such as endometrial cancer and vascular events.

Dr. Ford also showed findings from the recent Study of Tamoxifen and Raloxifene (STAR). The trial was designed to determine whether the osteoporosis drug raloxifene is as good as or better than tamoxifen in preventing invasive breast cancer in high-risk postmenopausal women. The large randomized trial looked at more than 19,000 women who were assigned to receive either drug daily for 5 years.

Initial results of the trial demonstrated that raloxifene is as effective as tamoxifen in preventing invasive breast cancer. "Adverse-effect profiles varied for the 2 drugs, providing at-risk women a choice of agents for breast cancer prevention based on medical history and personal preference," Dr. Ford said.

"More recently," she added, "aromatase inhibition has demonstrated superiority over tamoxifen in reducing both breast cancer recurrence and contralateral breast cancer." Clinical trials are under way in North America and the United Kingdom comparing exemestane and anastrozole with placebo in postmenopausal women. "The logical next step would be to compare raloxifene as used in STAR with an aromatase inhibitor such as letrozole in high-risk postmenopausal women," Dr. Ford said. Plans are under way for this study to be conducted by the National Surgical Adjuvant Breast and Bowel Project.

During the discussion period following the session, an attendee from Chicago congratulated Dr. Ford on her presentation. "Thank you for leading this national prevention effort," she said.

The Search for Other Interventions

In a second talk at the same session, Carol Fabian, MD, from the University of Kansas Medical Center, in Kansas City, spoke of other possible strategies. "Despite the establishment of tamoxifen and raloxifene as primary-prevention agents, we continue to search for interventions with fewer side effects and broader efficacy," she said.

"Interventions currently being assessed in early prevention trials include third- and fourth-generation selective estrogen receptor modulators, COX-2 inhibitors, rexinoids, and aromatase inhibitors in postmenopausal women on hormone replacement therapy," Dr. Fabian said. Also in the works are studies of gonadotropin-hormone-releasing agonists plus low-dose hormones in premenopausal women, phytoestrogens and lignans, tyrosine kinase inhibitors, and lifestyle interventions such as diet and exercise.

During an interview with Medscape, Dr. Kalidas emphasized the importance of lifestyle interventions. "We know that exercise can help reduce the risk of recurrence and new cancers in ER-positive patients. This is also a good idea for a variety of diseases and would be a good place for practicing oncologists to start with regard to prevention strategies," she said. "It's always a good thing to remind patients of the importance of a low-fat, high-fiber diet and regular exercise."

29th Annual SABC Symposium: Abstracts MS4-1 and 2. Presented December 16, 2006.

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