Medication Halts Cancer Recurrence In Many Women

Letrozole Follows Tamoxifen Therapy

Breast cancer patients taking the medication letrozole, following five years of tamoxifen therapy, had about half the rate of cancer recurrences as women taking a placebo (inactive substance).

Letrozole is one of a new class of medications called aromatase inhibitors.

While tamoxifen works by occupying the estrogen receptor and preventing the hormone from binding, letrozole goes further and actually blocks production of the hormone.

Because the results were so promising, investigators halted a major international trial of the new medication early.

"The results are absolute, confirmed, and credible," study investigator Dr. Paul Goss said at news conference. "An independent monitoring committee recommended that we stop the study by preset statistical boundaries, which we exceeded by at least 10-fold."

Dr. Goss is also the lead author of a special, early-release article detailing the findings in the New England Journal of Medicine.

Tamoxifen First, Letrozole Follows

Tamoxifen has been a great boon to women who have estrogen-receptor-positive breast cancer, meaning cancer that is fueled by the hormone estrogen. The medication reduces the risk of recurrence by 47 percent and the risk of death by 26 percent for five years after surgery.

Unfortunately, tamoxifen stops working after that time and may even reverse its action, promoting the growth of cancer cells.

"What is unrecognized is that over 50 percent of recurrences unfortunately occur beyond five years after diagnosis," Dr. Goss said. "Because it continues to relapse almost indefinitely, there is no limit to the disease."

The letrozole trial started enrolling participants in 1998. At this point in time the study has enrolled 5,187 women in Canada, the US, and Europe who were postmenopausal, had hormone-receptor-positive tumors, and had been on tamoxifen for about five years (the range was four-and-a-half to six years).

All of the women had to be within three months of stopping tamoxifen and all were disease-free when enrolled. The trial was coordinated by the National Cancer Institute of Canada.

The participants were randomly assigned to receive either 2.5 milligrams of letrozole or a placebo daily for five years. Letrozole reduced the risk of recurrence by 43 percent.

The median follow-up was only 2.4 years when the trial was stopped.

"This is one more example of the ability of to interrupt the progression of a cancer using a drug that blocks a crucial metabolic pathway in the tumor cell," says Dr. Andrew von Eschenbach, director of the National Cancer Institute (NCI).

Tamoxifen Compared with Letrozole

Side effects in the placebo and letrozole groups were roughly equivalent, except the rate of bone thinning was slightly higher with letrozole.

Tamoxifen, by contrast, provides protection against bone fractures, although it may contribute to endometrial cancer and blood clots. Women considering taking letrozole need to talk to their physicians about ways to mitigate the risk of osteoporosis.

Letrozole has already been approved by the US Food and Drug Administration (FDA) for some forms of breast cancer.

"I would think that there would be sufficient basis to use this as a pivotal trial to justify an amendment to their indication," said Dr. James Ingle of the Mayo Clinic and another investigator on the trial.

Ultimately, getting another [FDA] approval would be up to the medication's maker, Novartis, which provided letrozole for the new study.

There are some drawbacks to stopping a trial early, namely the number of unanswered questions about side effects and the continued effectiveness of the drug over time.

Current and future studies of aromatase inhibitors will look at a range of issues, including whether letrozole could be used instead of tamoxifen, whether it could be used if women had been off for tamoxifen for longer than three months, whether it works in an equivalent fashion, and whether the success of letrozole will continue over longer time frames.

"This large trial only began in 1998 and we already have important results that will change clinical practice," says Dr. Jeffrey Abrams, coordinator of the NCI Cooperative Group breast cancer treatment trials. "This is a tribute to the patients and physicians who participated since their efforts will now have a positive impact on so many lives."

Always consult your physician for more information.

What Are Aromatase Inhibitors?

According to the American Cancer Society (ACS), aromatase inhibitors include three medications that stop estrogen production, and these currently are approved for use in treating breast cancer.

These medications are called letrozole (Femara®), anastrozole (Arimidex®), and exemestane (Aromasin®). They work by blocking an enzyme responsible for producing small amounts of estrogen in postmenopausal women.

These breast cancer treatments cannot stop the ovaries of premenopausal women from producing estrogen. For this reason they can only be used in postmenopausal women.

The ACS states that "many physicians prefer these medications to tamoxifen as the first hormonal treatment for postmenopausal women whose breast cancer has come back, if the cancer is hormone receptor positive."

Aromatase inhibitors have been compared with tamoxifen as adjuvant hormone therapy. ACS explains that these medications have fewer side effects than tamoxifen because they do not cause endometrial cancer and very rarely cause blood clots.

They can, however, cause osteoporosis and bone fractures because they remove all estrogens from a postmenopausal woman.

Always consult your physician for more information.

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November 2003

Medication Halts Breast Cancer Recurrence In Many Women

Tamoxifen First, Letrozole Follows

Tamoxifen Compared with Letrozole

What Are Aromatase Inhibitors?

Treatment Shorter, and Fewer Side Effects

Experts Want More Study

Online Resources

New Study Looks at Limited-Field Radiation after Breast Cancer Surgery 

A woman with breast cancer who undergoes limited-field radiation after surgery has similar survival and recurrence rates as a woman who receives whole-breast radiation, researchers report in the Journal of the National Cancer Institute.

"For about 10 years, we have been looking at whether limited-field radiation, which limits radiation to the tumor site and a small surrounding area, is as effective as treating the whole breast in patients with early-stage breast cancer," says Dr. Frank A. Vicini, the chief of oncology at William Beaumont Hospital in Royal Oak, Mich.

The findings from the current study represent five-year results of 199 women with early-stage breast cancer who were treated with limited-field radiation after breast-conserving surgery.

Dr. Vicini and his colleagues compared these women with 199 similar women who were treated with whole-breast radiation therapy.

Treatment Shorter, and Fewer Side Effects

The researchers found that for women in both groups there was no difference in the median time to the recurrence of cancer or to recurrence of cancer at the same location.

Dr. Vicini's team also found that there was no difference between the women in the spread of cancer beyond the breast or in survival.

The advantages of limited-field radiation therapy include a shorter treatment cycle - five days compared with six weeks for whole-breast radiation - and fewer side effects, Dr. Vicini says.

"These results look good," Dr. Vicini says. "But are they good enough to say that this is the standard of care?"

While randomized trials that compare both treatments are going on in Europe, Dr. Vicini would like to see a randomized study done in the US.

The advantage of such a study is that it would identify the kind of patients most likely to benefit from limited-field radiation therapy.

The disadvantage is that it will take many years to complete. In the meantime, physicians are offering limited-field radiation therapy now, Dr. Vicini says.

He cautions that limited-field radiation therapy, like many other therapies, may become the standard of care without proper study.

Dr. Vicini says limited-field radiation is appropriate therapy in a select group of patients, namely those women with an early-stage cancer that has not spread to the lymph nodes and has a clearly defined tumor.

The treatment will be beneficial to most women with early-stage cancer who undergo breast-conserving surgery, Dr. Vicini says.

Dr. Vicini advises women currently considering limited-field radiation to discuss the treatment with their physician.

Experts Want More Study

In an editorial in the journal accompanying the study, Dr. Paul Wallner, the chief of radiation oncology at the National Cancer Institute (NCI), and his colleagues recommend randomized trials before limited-field radiation therapy is widely used.

"But we recognize that physicians will use this therapy now and trials will take a long time," Dr. Wallner says.

"We are raising a note of caution," Dr. Wallner says. "One of our concerns is that people will think this therapy is applicable to a different group of patients than it was tested on."

Dr. Wallner says patients may elect to have the therapy, but they need to have all the data, so they should ask their physicians.

"Physicians should be sure to tell their patients that the results are based on small studies among highly selected patients," he adds.

Always consult your physician for more information.