Extending adjuvant letrozole from 2.5 to 5 years does not improve disease-free survival or overall survival outcomes among women with breast cancer, but might be associated with reduced risk of a second primary breast tumor, according to findings from the phase 3 IDEAL Trial, presented at the 2016 San Antonio Breast Cancer Symposium.

“There were no significant differences in disease-related outcomes,” reported Erik J. Blok, MD, of the department of medical oncology, Leiden University Medical Center in Netherlands. “There is no benefit of extending AI-based adjuvant therapy longer than 2.5 years.”

There was a high frequency of adverse events, with 70% of patients in each study arm experiencing toxicities. The most common toxicities were arthralgia (14%), hot flashes (12%), and osteoporosis (10%).

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Adjuvant endocrine therapy with aromatase inhibition (AI) or tamoxifen is the mainstay of breast cancer treatment. AI appears to be superior to tamoxifen in the first 5 years, whether delivered sequentially or up-front, Dr Blok noted.

The new study was undertaken to analyze whether adjuvant letrozole should be extended to 2.5 years or 5 years.

Patients were enrolled at 74 hospitals across the Netherlands between 2007 and 2011. A total of 1821 eligible patients were included in the study. Median follow-up was 6.5 years, and 1338 were available for secondary analysis after disease progression events in 483 patients.

Toxicities “had an effect on compliance,” Dr Blok noted. A total of 241 patients in the 2.5-year study arm stopped treatment early, of whom 179 (74%) stopped because of adverse events and drug refusal. In the 5-year group, 385 patients stopped early, of which 254 (66%) stopped because of adverse events and drug refusal.

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In subsequent competing risk modeling, the research team did identify a significant difference in the prevention of second primary breast tumors, with a hazard ratio (HR) of 0.37, a “small absolute risk reduction of 1% at 5 years,” Dr Blok noted. “This was similar to findings in healthy women.”

Prevention of new primary breast tumors should be explored as a possible therapy goal for adjuvant therapy, he suggested.


  1. Blok EJ, van de Velde CJH, Meershoek-Klein Kranenbarg EM, et al. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05). Paper presented at: 39th San Antonio Breast Cancer Symposium; December 2016; San Antonio, TX.