乌鸦传媒

CHICAGO -- An extra 5 years of the aromatase inhibitor letrozole (Femara) continues to reduce the risk of breast cancer recurrence, a researcher said here.

In a phase III trial, postmenopausal women who had already taken the drug or another aromatase inhibitor for 5 years were randomly assigned to take it or a placebo for another 5, according to , of Massachusetts General Hospital Cancer Center in Boston.

The additional therapy significantly reduced the risk of recurrence and the occurrence of contralateral breast cancer, but had no effect on overall survival, Goss reported at the American Society of Clinical Oncology annual meeting, and online in the .

Goss told 乌鸦传媒 the results are sufficiently strong that the "default" for postmenopausal women who have had 5 years of an aromatase inhibitor should be to continue.

"If the patient is tolerating the aromatase inhibitor well, the quality of life is good, and the recent bone mineral density is good, why not?" he said.

Goss was principal investigator of the 2003 landmark MA.17 trial, which showed that 5 years of letrozole after tamoxifen markedly reduced the risk of breast cancer recurrence.

The new study (MA.17R) should set a "new standard for treating postmenopausal women with estrogen-receptor-positive breast cancer," commented , of Harbor-UCLA Medical Center in Torrance, Calif.

But that is likely to come with another challenge, he told 乌鸦传媒.

"I think the standard will change," he said, "and many people are going to get to 10 years of an aromatase inhibitor, and we're going to end up scratching our heads to say 'What do we do now?'"

In an accompanying NEJM editorial, Chlebowski and , also of Harbor-UCLA, noted that the toxicity associated with the regimen was "really very low."

But of Washington University in St. Louis, who was not involved in the study, cautioned that the benefit, mostly in prevention of contralateral cancers, was "relatively modest" and the toxicity was not inconsequential.

"A risk-benefit decision has to be made in terms of the toxicity of the treatment and the value of the reduction of breast cancer," he told 乌鸦传媒.

The study investigators enrolled 1,918 postmenopausal women with primary breast cancer who remained free of disease after a median of 5 years of adjuvant therapy with an aromatase inhibitor. For about 80% of patients, that therapy was preceded by treatment with tamoxifen.

Patients were randomly assigned to take 2.5 mg daily of letrozole or placebo for another 5 years.

The primary endpoint of the study was disease-free survival (DFS), which the investigators defined as the time from randomization to recurrence of the original breast cancer, or the development of a new primary breast cancer.

Goss and colleagues found 165 participants had either recurrent disease or occurrence of contralateral breast cancer, including 67 taking letrozole and 98 getting placebo.

The numbers indicated that the rate of 5-year DFS was 95% for letrozole and 91% for placebo, with a hazard ratio (HR) favoring letrozole for disease recurrence or the occurrence of contralateral cancer of 0.66 (95% CI 0.48-0.91), which was significant (P=0.01).

On the other hand, the major difference was in the occurrence of contralateral disease -- 13 in the letrozole group versus 31 in the placebo group -- compared with 55 recurrences for letrozole and 68 for placebo.

Annually, the incidence rate for contralateral disease was 0.21% for letrozole and 0.49% for placebo, for an HR 0.42, which was significant (P=0.007).

There was no significant difference in overall survival at 93% with letrozole and 94% with placebo, Goss reported.

As expected, the major difference in adverse events were those associated with letrozole as patients getting the drug had a higher incidence of bone pain, bone fractures, and new-onset osteoporosis.

But the incidence of such effects was relatively low, perhaps because patients prone to them during their previous letrozole therapy simply did not seek to enroll in the new study, Goss said. "These are highly selected patients," he said, "who are not the ones who are having very severe symptoms who have typically dropped out before."

In a separate presentation on patient-reported outcomes from the MA.17R trial , , of Laval University in Quebec City, said her group collected patient-reported outcomes using the SF-36 health survey and the Menopause-specific Quality of Life questionnaire.

There were no clinically meaningful differences between the groups on any of the outcome measurements, she told reporters.