Letrozole Reduces Risk Of Breast Cancer Recurrence And Metastasis Even If Started Years After Tamoxifen

Main Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 12 Mar 2008 - 4:00 PDT

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A multicenter phase III clinical trial has reported that the drug letrozole cuts the risk of breast cancer recurrence by 63 percent and the risk of cancer spread by 61 percent in postmenopausal women with early-stage disease who completed five years of tamoxifen therapy one to seven years earlier. The study is being published online March 10 in the Journal of Clinical Oncology (JCO).

"While tamoxifen has been a very important and effective part of breast cancer treatment, more than half of all recurrences and two-thirds of breast cancer deaths still occur after five years of tamoxifen therapy," said lead author Paul Goss, MD, professor of medicine at Harvard Medical School. "Our study suggests that women who finished tamoxifen even several years ago may benefit from taking letrozole to further reduce their risk."

Letrozole (an "aromatase inhibitor") works by blocking an enzyme needed to make the estrogen that most breast cancers need to grow. Women with early-stage breast cancer fueled by estrogen ("estrogen-receptor positive") typically receive five years of tamoxifen to reduce their risk of recurrence. Letrozole is currently approved for breast cancer treatment immediately after surgery or within three months of completing five years of tamoxifen treatment.

The studyâ€"called the MA.17 study, led by the National Cancer Institute of Canada Clinical Trials Groupâ€"reported in 2003 that letrozole was effective at reducing the risk of breast cancer recurrence if initiated shortly after completing tamoxifen. The new data show that this benefit persisted even among women who had finished tamoxifen one to seven years before starting letrozole. Among 1,579 women who had been taking a placebo in the earlier part of the study and then switched to letrozole, 95.1 percent remained free of breast cancer six years later and 97.7 percent remained free of metastasis, compared with 91 percent and 95.6 percent, respectively, of the 804 women who continued taking a placebo. Women in the letrozole group also experienced an 82 percent reduced risk of a second cancer in the opposite breast.

In a separate analysis of that same trial, researchers-led by Hyman Muss, MD, professor of medicine at the University of Vermont-found that the reduced risk of breast cancer recurrence persisted among all age groups, including women over 70, who are sometimes given less aggressive therapy due to concerns over side effects and magnitude of benefit. There were no differences in the side effects of letrozole or quality of life between the different age groups.

Letrozole was well tolerated by the large majority of patients. The primary increased side-effect among women who received letrozole was bone fractures and osteoporosis, compared with those on placebo (5.2 versus 3.1 percent). Doctors generally recommend that women have their bone health assessed before starting aromatase inhibitor therapy.

Exemestane Cuts Recurrence by More than 50 Percent

Another study in the same issue of JCO showed that taking another aromatase inhibitor, exemestane (Aromasin), soon after completing tamoxifen treatment reduces the risk of recurrence by 56 percent. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-33 Trial was stopped early when the 2003 MA.17 letrozole results were reported, and women receiving a placebo were offered exemestane. In the current study-led by Eleftherios P. Mamounas, MD, associate professor of surgery at Northeastern Ohio University College of Medicine-96 percent of the women who were originally designated to receive exemestane remained free of recurrence after four years, compared with 94 percent of those taking a placebo.

Exemestane was well tolerated by most of the women. It is currently approved for women who have completed two to three years of tamoxifen and switch to exemestane to complete the five-year course of hormonal therapy.

Editorial Cites Need for "Paradigm Shift"

In an editorial accompanying these studies, Nancy U. Lin, MD, and Eric P. Winer, MD, both of the Dana-Farber Cancer Institute, wrote: "The results of MA.17 and NSABP B-33, taken in context with the other adjuvant endocrine trials reported in the last five to seven years, strongly argue for a paradigm shift in the clinical research focus and management of patients with estrogen receptor-positive breast cancer...We need to identify predictors of late recurrence and treatment approaches that will change the low, but unrelenting, risk of recurrence seen in patients with estrogen receptor-positive breast cancer. Perhaps most importantly, we need to recognize the heterogeneity of both breast cancer and patients with breast cancer, in order to develop individualized treatment strategies that lead to the greatest benefit while minimizing risk."

"Late Extended Adjuvant Treatment with Letrozole Improves Outcome in Women with Early-Stage Breast Cancer Completing 5 Years of Tamoxifen."
Paul E. Goss et al.

"Efficacy, Toxicity and Quality of Life in Older Women with Early Stage Breast Cancer Treated with Letrozole or Placebo after Five Years of Tamoxifen: NCIC CTG Intergroup Trial MA.17."
Hyman B. Muss et al.

"Benefit from Exemestane as Extended Adjuvant Therapy Following Five Years of Adjuvant Tamoxifen: Intent-to-Treat Analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 Trial."
Eleftherios P. Mamounas et al.

"Optimizing Endocrine Therapy for Estrogen Receptorâ€"Positive Breast Cancer: Treating Patients for the Right Length of Time."
Nancy U. Lin and Eric P. Winer.

A consumer information piece on this study can be found on ASCO's patient website, People LivingWith Cancer.org, at http://www.plwc.org/CancerAdvances. For more information about breast cancer treatment, visit http://www.plwc.org/breast.

The Journal of Clinical Oncology is the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world's leading professional society representing physicians who treat people with cancer.

http://www.asco.org

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