Aromatase Inhibitor Benefit Post-Tamoxifen Called Limited

PHILADELPHIA, Oct. 23 -- For most women with early breast cancer, following five years of tamoxifen with an aromatase inhibitor will bring only a slight improvement in disease-free survival, calculated researchers here.

In a study of 471 women who had been treated with tamoxifen and remained cancer-free for five years, adding an aromatase inhibitor would have increased the recurrence-free survival rate by between 1% and 2%, found Gary Freedman, M.D., of the Fox Chase Cancer Center here, and colleagues.

On the other hand, some subgroups of women would derive a greater benefit, Dr. Freedman and colleagues reported in the Dec. 1 issue of Cancer.

"Based upon our findings, women who are premenopausal at the time of initial therapy and patients who have four or more positive lymph nodes will have the greatest potential benefit from the addition of extended adjuvant anti-estrogen therapy," the researchers concluded.

For women older than 60, the decision to use aromatase inhibitors should be "individualized based upon their initial nodal status and presence of comorbidities that would reduce their five-year life expectancy," Dr. Freedman and colleagues added.

The conclusions were based on an analysis of a cohort of women with early stage breast cancer who underwent breast-conserving surgery, axillary node dissection, radiation therapy, and tamoxifen from September 1982 to November 1999, with at least five years of follow-up after radiation.

To be eligible for this study, Dr. Freedman and colleagues said, women had to be disease-free during the five years of tamoxifen therapy. They were then followed for at least another five years, during which none of the volunteers was treated with an aromatase inhibitor.

There were 36 adverse events during the study, the researchers said: 10 contralateral breast cancers and 26 recurrences, of which eight were local, one was regional and 17 were distant.

Taking the whole follow-up period into account, the 10-year risk of:

• Locoregional recurrence was 2.5%.
• Contralateral breast cancer was 3.6%
• Distant metastasis was 4.4%.
• The recurrence-free survival rate for all patients was 93% and the overall survival rate was 89%.

One major study showed a 42% relative reduction in the risk of disease recurrence if tamoxifen therapy was followed by the aromatase inhibitor Femara (letrozole), the researchers noted.

"In the current study, a 40% improvement in the 10-year event-free survival rate of 93% would result in a rate of approximately 96%," Dr. Freedman and colleagues said, but that 3% improvement was mostly limited to women who were either premenopausal at the time of initial treatment or who had four or more positive lymph nodes.

In women with one to three positive nodes, the event-free survival was between 94% and 97% at 10 years, "suggesting only a 1% to 2% potential for absolute risk reduction during this time period," the researchers said.

While the improvement is real, the researchers noted, it must be weighed against other factors, including cost and adverse events associated with the aromatase inhibitors. They noted that the price of Femara is more than per month.

"For low-risk women, the risk of a decrease in a breast cancer-related event of 1% to 2% might equal the risk of a side effect," the researchers said.

"The consequence of the side effect will need to determine whether the benefit outweighs the risk. For example, even a small increased risk of 1% to 2% for osteoporosis or fracture may be unacceptable in low-risk patients given the enormity of the cost (approximately billion to billion per year) and consequences (hospitalization, institutionalization, increased mortality) of this disease to individuals and society in general."