Old Treatments -- Tamoxifen, Radiation, HRT -- Repurposed into New Combinations that Extend Survival

One of the most important recent cancer treatment findings has resulted from a follow-up to the International Breast Cancer Intervention Study (IBIS-1), the global breast cancer prevention study.

Tamoxifen Benefits

When initial results were announced four years ago, tamoxifen was shown to reduce by one-third the risk of estrogen-positive (ER-positive) cancer in high-risk women. Now results from a randomized 96-month follow-up of 7,000 women shows this protection lasts at least five more years after the drug is discontinued.

For women who stopped tamoxifen because of the risk of dangerous side effects like endometrial cancer and blood clots, the study showed that these disappeared once tamoxifen use was curtailed. The researchers suggested “that the risk-benefit ratio would continue to improve with longer follow-up time.”

HRT Tamoxifen Combination

The news for women on HRT and tamoxifen was mixed. Because HRT increases the chance of developing ER-positive breast cancer, doctors had hoped that adding tamoxifen to the mix would cut risk. Those whose HRT treatment was limited to pre-trial use and stopped when they began tamoxifen did experience a significant reduction in ER-positive cancers.

But the endometrial cancer and blood clots, the study showed that these disappeared once tamoxifen use was curtailed. The researchers suggested “that the risk-benefit combination of HRT and tamoxifen did not demonstrate a clear benefit in preventing more disease. Nor did tamoxifen prove effective in reducing risk of ER-negative breast tumors.

IBIS-2, the next phase of the study, will investigate whether the armoatase inhibitor anastrozole has lesser side effects than tamoxifen, and if it is more potent in preventing breast cancer in post-menopausal women.

To Radiate or Not?

Most women would prefer not to undergo radiation because of its side effects, unless its use is essential to save their lives. Two new studies explored when radiation might be optional for older women.

The first involved women with low-risk ductal carcinoma in situ (DCIS)—noninvasive breast cancer—and analyzed whether localized surgery to remove the tumor was sufficient to prevent a recurrence in the same breast. About 700 women (average age 60) with low-, intermediate- or high-grade tumors participated in a five-year trial.

All were initially treated with local surgery only, without radiation. In year three of the study, optional voluntary use of tamoxifen was permitted.At five years, those with low- to intermediategrade tumors had an acceptably low risk of recurrence, but results suggested that for highgrade tumors, surgery alone was not effective in preventing recurrence.

Tamoxifen without Radiation an Option

In another study, researchers set out to discover if older women benefited sufficiently from radiotherapy plus tamoxifen after breast-conserving surgery to outweigh the side effects of radiation. The study involved 600 women aged 70 and older with ER-positive Stage I breast cancer. All study participants underwent a lumpectomy prior to being randomized to receive either tamoxifen alone or tamoxifen plus radiation.

While the addition of radiation cut their chances of local breast cancer recurrence by six percent, at eight years overall survival was the same as the women who took only tamoxifen. Despite the decrease in cancer recurrence, the irradiated women were less pleased with their appearance afterwards compared to those not irradiated.

The study concluded that for women over 70 with ER-positive Stage I cancer, a treatment regimen of lumpectomy followed by tamoxifen without radiation is a viable option. Results were presented at the 29th Annual San Antonio Breast Cancer Symposium (SABCS) held in December.

An Expert's Perspective

"The findings from the IBIS-1 are similar to U.S. studies, which showed an even greater reduction of 50 percent," says Debbie Saslow, PhD, breast and gynecologic cancers director for the American Cancer Society.

"Results from the DCIS study suggest that low-risk women may be treated without radiation treatment. But women with intermediate-risk DCIS need excision followed by radiation. Looking at older women who received a lumpectomy to remove early stage breast cancer, data showed that tamoxifen plus radiation had little benefit over tamoxifen alone.

Since these women had stage 1 ER-positive breast cancer, their prognosis was actually very good. While the study was fairly small, it's important because few studies have looked at women in this age group."