RESEARCH LEADER COMMENTARY

Chemoprevention of breast cancer

NSABP-P-1 demonstrated a proof of principle. Tamoxifen prevented the clinical expression of breast cancers in about 50 percent of women at high risk. Epidemiologists question whether this is true prevention, or whether we're simply treating early at the level of phenotypic expression. That's possible, and I'm certain that there will be other candidates for prevention, such as the aromatase inhibitors. These agents have less toxicity, which will make them ideal agents for testing in the prevention setting.

As the mechanisms for detecting breast cancer improve, we are going to detect more lesions that are "preventable." The prognosis for these women is so good that we don't see why we should treat them. However, in the prevention mode we are treating these women and are very happy to reduce their risk of breast cancer by 50 percent. We are in a conundrum: "Should we treat them or not?"

— Bernard Fisher, MD

Aromatase inhibitors for prevention in postmenopausal women

Considerably fewer vasomotor symptoms and problems with weight gain are associated with aromatase inhibitors than with tamoxifen. While these are anecdotal observations, I have seen these differences in my own practice so often that I'm fairly certain they will prove to be true.

Perfectly healthy women considering prevention have a different level of motivation and tolerance of side effects than breast cancer patients who have been thrust into menopause by chemotherapy. The aromatase inhibitors are very well-tolerated and very safe, and I think if clinical trials demonstrate a positive therapeutic ratio for aromatase inhibitors, healthy women with even the slightest motivation to reduce their breast cancer risk will find them acceptable.

— Paul E Goss, MD, PhD, FRCP(CA), FRCP(UK)

ATAC: Research implications for prevention

If we look at the ATAC data, the improvement in terms of contralateral breast cancer risk is impressive. It is over 50 percent better than what we have achieved with tamoxifen. If the prevention trials with the aromatase inhibitors are positive, then the discussion will be easier than it ever was for us with tamoxifen, because tamoxifen was virgin territory. We had to begin with no understanding about chemoprevention. There was a whole process of educating physicians and patients, and that has been done.

The major obstacle for the use of tamoxifen in women at high risk is their fear of endometrial cancer and thrombosis. Some women are concerned about hot flashes and quality-of-life issues, and I think when you eliminate those fears, it'll be much easier to convince women to utilize a chemoprevention strategy.

— Generosa Grana, MD

IBIS-II trial

IBIS-II, a prevention trial, will compare anastrozole to placebo in women at high risk of developing breast cancer. In the United Kingdon, tamoxifen as prevention has not caught on because it has a high rate of morbidity. The IBIS-I study showed a very minimal effect and considerable morbidity with tamoxifen. Anastrozole looks like a better agent than tamoxifen for prevention, so I agree with the direct comparison to placebo.

Based on the ATAC trial data, I would expect anastrozole to dramatically decrease the number of breast cancers that develop. I think anastrozole should be superior to tamoxifen in that setting.

— J Michael Dixon, MD, FRCS

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