A Better Drug for Advanced Breast Cancer?

Summarized by Robert W. Griffith, MD
December 19, 2001 (Reviewed: December 5, 2003)

Introduction

Some breast cancer cells are hormone-dependent, and one way to attack them is to interfere with their supply of hormone. The aromatase inhibitors are drugs that prevent the conversion of androgen into estrogen - in other words, they limit the amount of available estrogen. Tamoxifen (Novaldex), which blocks the action of estrogen by another mechanism, is widely used to treat hormone-dependent breast cancer that is in an advanced stage (i.e. there are secondary cancer deposits in other sites, such as the bone or the liver, or the cancer has occurred again at the original site).

This sort of endocrine therapy is at least as successful as cytostatic drugs ('chemotherapy') in treating hormone-dependent advanced breast cancer, and it's much better tolerated. Tamoxifen, which has been available for over 10 years, is usually prescribed, but recently improved aromatase inhibitors have been developed. One of them, anastrozole, has shown a similar response rate to tamoxifen in two studies. Another, letrozole, has been reported to be superior. Here are the findings from a large study with letrozole reported in the Journal of Clinical Oncology.

The study

This study was done at 201 cancer centers in 29 countries. Postmenopausal women with advanced breast cancer were asked to volunteer for the study; they were not included if tests showed that their cancer cells were not hormone-dependent. Very ill patients or those with extensive metastases were, of course, excluded.

Patients took letrozole (2.5 mg once daily) or tamoxifen (20 mg once daily), until progression of their disease was diagnosed. At this point, they were given the option of taking the alternative drug, if they wished.

The effectiveness of the two drugs was determined by measuring the 'time to progression', which was the time from the start of the study until the earliest date that progression of the disease was diagnosed. This was defined as an increase of 25% in the number or size of tumors, the appearance of new tumor, stopping medications because of general illness, or death. Other measures of effectiveness were also used; they included: the tumor response rate, the rate and duration of clinical benefit, the time to treatment failure, and overall survival. Side effects were also carefully assessed.

Results of the study

A total of 907 patients were enrolled - 453 on letrozole, and 454 on tamoxifen. The vast majority of them had 'secondaries' (or metastases), mostly in the soft tissues, bone or liver. The average duration of treatment was 18 months.

The average time to progression was greater for letrozole patients than for those on tamoxifen; 41 and 26 weeks, respectively. This difference between treatments was statistically significant. The same effect was seen with the average time to treatment failure (40 and 25 weeks).

The overall response rate (the percentage of patients who showed a clinically positive response to treatment at 1, and then 3 month intervals after starting the study) was higher in letrozole group (30%) than in the tamoxifen group (20%). This effect, too, was significant.

Most patients reported at least one side effect of the medication, but the side effects were about the same in both treatment groups. The commonest were hot flushes, nausea, and thinning of the hair. There were none of the severe side effects usually associated with 'chemo'.

Comment

In the war against cancer, progress is made in small steps, rather than in giant strides. Endocrine treatment for advanced breast cancer is not the final answer - the very fact that progression of the disease is used as a measure of effectiveness, rather than the cure rate, shows how far we have to go. However, small steps add up, over time, to major improvements.

In this study letrozole was clearly more effective than the established first-line endocrine treatment, tamoxifen. (This was the case even in the 1/3 of patients where the endocrine status of their tumors was unknown.) On the other hand, the safety and side effect profiles of the two drugs were similar. This makes letrozole an obvious new choice for first-line treatment.

Source

• Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer. H. Mouridsen, M. Gershanovich, Y. Sun,  et al., J Clin Oncology, 2001, vol. 19, pp. 2596--2606

Related Links
Review: The Cancer Patient's Workbook
Breast Cancer in Older Women
Active Lifestyle May Reduce the Risk of Breast Cancer

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