This article originally appeared in the April 2002 Harvard Women's Health Watch and is provided courtesy of Harvard Health Publications.

New Breast Cancer Drugs Expand Treatment Options

Tamoxifen is often prescribed to reduce the chance of first-time breast cancer in women at high risk, or to prevent recurrence in women who have already been diagnosed. Soon, there may be another — perhaps better — option for postmenopausal women who are at risk for or have this disease.

At the 2001 San Antonio Breast Cancer Symposium, researchers reported promising results from three large studies comparing tamoxifen to aromatase inhibitors in postmenopausal women with breast cancer. Aromatase inhibitors are a new class of drugs that work by blocking aromatase, an enzyme critical to the production of estrogen in postmenopausal women. Tamoxifen, in contrast, blocks estrogen at receptor sites on breast cancer cells, preventing it from stimulating cell growth.

Data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial showed a significant reduction in deaths, recurrences, ductal carcinoma in situ, and contralateral breast cancer (a subsequent cancer occurring in the other breast) in women taking the aromatase inhibitor anastrozole (Arimidex) versus those receiving tamoxifen.

The 9,000 participants in ATAC — the largest randomized trial to study cancer patients — were postmenopausal and newly diagnosed with either estrogen receptor-positive breast cancer or early stage breast cancer of unknown type. Subjects who took the anastrozole alone had about 60% fewer incidences of contralateral breast cancer than women in the other two groups. Already approved for preventing a recurrence of the disease, aromatase inhibitors aren’t yet sanctioned, as tamoxifen is, for primary prevention.

Given these results, it might seem that doctors and patients should consider switching to anastrozole. But ATAC is only a single trial, albeit a good one, and more data are needed. For example, women in the study who took anastrozole suffered more bone fractures and joint pain than those taking tamoxifen. On the other hand, subjects receiving anastrozole were less likely to report hot flashes, weight gain, or vaginal bleeding or dryness, or to develop blood clots or endometrial cancer.

The San Antonio conference presented other studies and also analyzed past research comparing tamoxifen to aromatase inhibitors. The findings included:

• Tumor response to treatment. Each of the three approved medications — anastrozole, letrozole (Femara), or exemestane (Aromisin) — managed tumors as well as or better than tamoxifen.

• Time until tumor regrowth. The time it took tumors to start growing again was at least as long for breast cancer patients taking an aromatase inhibitor as it was for those receiving tamoxifen.

• Side effects. Trials that tested tamoxifen against all three aromatase inhibitors reported that participants suffered similar side effects, regardless of which drug they took. These included menopausal symptoms, gastrointestinal problems, and aching in the joints.

Aromatase inhibitors are already approved for estrogen receptor-positive recurrent breast cancer. The new findings may lead to their use as a first-line treatment for breast cancer. Judy E. Garber, M.D., M.P.H., the director of the Cancer Risk and Prevention Program at Dana-Farber Cancer Institute, doesn’t believe that tamoxifen should be abandoned, but she thinks some postmenopausal breast cancer patients should consider this potential alternative. In particular, women who have or are at risk for blood clots, or who have a history of uterine cancer, might benefit from the new therapy.

However, women currently taking tamoxifen and doing well probably shouldn’t switch, especially until we have more studies on aromatase inhibitors’ long-term effects, including their impact on osteoporosis risk.