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An important trial has just been published in the New England Journal of Medicine by the Breast International Group (BIG) I-98 collaborative group, which looked at the comparison on letrozole versus tamoxifen in receptor positive early breast cancer.
Both drugs are used after initial treatment to
prevent the cancer from returning. They work by preventing
the production or activity of estrogen, which is associated with breast
cancer recurrence in postmenopausal women. However, they work differently,
which may account for the benefit of letrozole over tamoxifen.
Letrozole is from a class of drugs called aromatase inhibitors, which
block the production of estrogen whereas tamoxifen differs in that it
interferes with the activity of estrogen, not the hormone's production.
Previously, several studies have shown that aromatase inhibitors alone were superior to tamoxifen after five years of adjuvant treatment. It was unknown, however, whether sequential treatment with tamoxifen after aromatase therapy would prolong survival, which this trial attempted to answer.
The trial looked at monotherapy with tamoxifen, monotherapy with an aromatase inhibitor, letrozole, and two sequential treatments ie tamoxifen followed by letrozole and letrozole followed by tamoxifen to see whether disease-free survival (DFS) was improved.
Overall, the BIG I-98 study found that sequential treatments with letrozole and tamoxifen did not improve disease-free survival, nor was either letrozole or tamoxifen alone superior after 5 years of treatment.
One of the limitations of the study, however, was the selective crossover to letrozole from tamoxifen monotherapy based on the interim data that suggested supriority of the aromatase inhibitor. Had the switch not occurred, it is likely that the significance of letrozole over tamoxifen have been stronger.
What the study did confirm was that:
a) The frequency of relapses within 2 years was significantly reduced with letrozole compared with tamoxifen, especially among high risk women, ie those with involved lymph nodes, large tumours or vascular invasion.
b) Taking tamoxifen sequentially after an aromatase inhibitor did not lead to any added benefit.
Given recent new data on the long term risks associated with tamoxifen in the development of aggressive contralateral ER-negative disease, which confers a poorer prognosis, it makes more sense for women to take an aromatase inhibitor as their initial therapy.
The Big I-98 Collaboration Group (2009). Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer New England Journal of Medicine, 361 (8), 766-776 DOI: 10.1056/NEJMoa0810818