Don't Stop Your Breast Cancer Drugs Too Soon!

Summarized by Robert W. Griffith, MD
March 5, 2007

Summary

After their initial treatment for breast cancer, many women who are prescribed tamoxifen fail to take the full course of treatment - as many as 35% give up within a 3½ -year period, putting them at increased risk of recurrence and death.

Introduction

It's been standard practice for women with hormone-responsive breast cancer to be prescribed tamoxifen (a selective estrogen receptor modulator) for 5 years. This has been shown to result in a 46% decreased risk of recurrence, and a 26% decreased risk of death. However, these beneficial results were obtained in clinical trials, where patients' adherence to their prescriptions is, as a rule, carefully checked. It's also been found that women given tamoxifen for less than 5 years have significantly higher recurrence rates and mortality. This means that non-adherence to tamoxifen therapy is likely to result in a worse outcome for these patients.

Adherence to a medication regimen (sometimes called compliance) is defined as the extent to which patients take their drugs as prescribed by their physician. It's usually reported as the percentage of the prescribed doses of a medication actually taken over a given period. The term persistence is used to describe continuous therapy on the same drug over a long period. This can be measured as the percentage of patients who continue to take their medication each month for a given period. Prescription refill data are commonly used to obtain this information.

Persistence is probably the best measurement of adherence in the case of breast cancer; most patients will start on their tamoxifen, and become more lax as time goes by without any evidence of recurrence. Researchers from Trinity College Dublin have studied this problem, and published their findings in the journal Cancer; here's a summary of their findings.

What was done

The information used in this study was taken from the Irish Health Services pharmacy database, which serves approximately a third of the Irish population. The subjects were women over 35 who commenced tamoxifen as initial hormone therapy between January 2001 and January 2004.

Tamoxifen non-persistence was defined as 180 consecutive days of no tamoxifen supply without alternative hormonal therapy (i.e. an aromatase inhibitor) during that time. This allowed non-persistent patients to be identified. Those with no prescription for any item in the 12 months after stopping tamoxifen were classified as 'lost to follow-up'; those with an alternative hormone prescription before the end of the 180-day no-tamoxifen period were classified as 'treatment switchers'.

All patients were followed for 1 to 3.5 years. Their age at the start of tamoxifen was determined. Based on prescription use, it was possible to identify patients who had received treatment for cardiovascular disease, respiratory disease, depression, psychoses, diabetes, cognitive impairment, and Parkinson's disease.

What was found

Of the 2,816 women included in the study, a third was over 75 years of age - a higher rate of estrogen-receptor responsive breast cancer is seen in this age group. The other 2/3 was spread fairly evenly among the remaining over-35 age groups.

A third of the participants had at least one of the accompanying conditions: diabetes, respiratory disease, or cardiovascular disease. The average number of prescription drugs taken was approximately 2 per month.

Using the agreed-upon definition, 22.1% of women in the study were identified as non-persistent after one year of starting treatment. Of these, 1.2% switched to another hormone treatment after 180 days without tamoxifen; 3.7% restarted tamoxifen after at least 180 days' discontinuation; and 1.4% restarted tamoxifen after a 1-year interval.

By the end of the follow-up period (3½ years) the non-persistence rate was 35.2%. This rate is higher than the 5-year rate found in clinical trials (reported as 16% to 32%). The women who discontinued tamoxifen early were at the age extremes - 35 to 44 and over 75; more likely to use antidepressants in the year before starting tamoxifen; and more likely to suffer from Parkinson's disease or dementia. There was no diagnostic or staging information about the subjects' breast cancer available, so their role in non-persistence could not be estimated.

What these results mean

The high rates of non-persistence, especially in the early stages of treatment, are likely to have a negative impact on the success of tamoxifen. Although not measured in this study, which dealt exclusively with the accurate measurement of treatment discontinuation, data from other studies are available that show the increase in recurrence and death that occur in those that stop the drug.

All this makes it more necessary to introduce measures to improve compliance. Practical steps include the identification and treatment of co-existing depression, the recognition and management of tamoxifen side effects, and handling any financial difficulties for the patient in acquiring the necessary medications. An additional factor - the perceived risk of recurrence of breast cancer is low in African Americans¹, pointing up the need for patient education in this population in particular.

Now it's reported that switching to an aromatase inhibitor after taking tamoxifen for 2 to 3 years offers a better outcome than staying on tamoxifen.² A switch to anastrazole (Arimidex^®) or aminoglutethamide (which is no longer used) resulted in significantly lower all-cause mortality and significantly lower cancer-related mortality. The important thing to realize is that, once again, the good results were obtained in clinical studies. The important thing is to ensure that there are no adherence problems, so that whether they are taking tamoxifen or Arimidex, the patients are actually taking their medications.

Source

• Early discontinuation of tamoxifen. A lesson for oncologists. Cancer 2007 online Barron TI, Connolly R, Bennett K, et al. http://www3.interscience.wiley.com/cgi-bin/fulltext/114084235/HTMLSTART accessed 2/12/07

Footnotes
1. Sociocultural predictors of breast cancer risk perceptions in african american breast cancer survivors. K. Brewster, EP. Wileyto, L. Kessler,  et al. , Cancer Epidemiology, Biomarkers, & Prevention, 2007, vol. 16, pp. 244--248
2. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma. F. Boccardo, A. Rubagotti, D. Aldrighetti,  et al., Cancer, 2007, vol. posted online: http://www3.interscience.wiley.com/cgi-bin/abstract/114114809/ABSTRACT accessed on 2/14/07.

Related Links
NCI: Aromatase Inhibitors
How to Avoid Breast Cancer - What To Do In Your 20s, 30s, and 40s
After you've Finished Your Breast Cancer Treatment
HRT Alternatives and Breast Cancer

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