Women who stop taking breast cancer drugs risk early death

“Breast cancer survivors who cut short preventative treatment ‘risk early death’,” The Guardian reports, saying that women who have only three years of preventative treatment rather than five are more likely to die earlier.

The newspaper reports on a Scottish study that looked at women who had been prescribed a course of hormone treatment after having surgery to treat oestrogen receptor positive breast cancer. In this type of cancer, cancerous cells are stimulated by the hormone oestrogen.

Drugs such as tamoxifen are used after surgery in order to prevent the cancer from returning. It is generally recommended that hormone treatments are taken for five years following surgery.

Looking at prescription data the researchers found women were on average less likely to stick to their treatment over time. This is known as adherence to treatment. In the first year, for example, women adhered to treament 90% of the time. This figure dropped to 50% by the fifth year.

The researchers found that women who had low adherence (those who took their drugs less than 80% of the time) over the five years of their treatment were at increased risk of death from any cause. However, there was no significant difference in risk of dying specifically from breast cancer in those with low adherence compared with those with high adherence, nor was there a difference in the risk of recurrence of breast cancer.

The researchers also looked at women who had good adherence (who took their drugs at least 80% of the time) but who stopped taking their treatment after three years or less. They found that these women were at increased risk of death from any cause, death due to breast cancer and recurrence of breast cancer compared with women who had good adherence for five years.

Limitations of the study include that its findings may not be applicable to other populations and that it relied on prescription data that may be inaccurate. But, overall, this study supports current treatment recommendations for a five-year period of hormone treatment following surgery for oestrogen receptor positive breast cancer.

Where did the story come from?

The study was carried out by researchers from the University of Dundee and the University of Glasgow and funded by Breast Cancer Campaign.

The study was published in the peer-reviewed British Journal of Cancer.

The Guardian’s reporting of the study is accurate and appropriate.

What kind of research was this?

This was a retrospective cohort study designed to review all women living in the Tayside region of Scotland who had been diagnosed with breast cancer between 1993 and 2008, who had been prescribed hormone therapy after they had been treated with surgery. This is called adjuvant hormone therapy – meaning it is given after surgery.

The study aimed to look at how long women were receiving prescriptions for hormone therapy for and whether women who persisted with treatment for longer had better outcomes (including survival) than those who didn’t.

Hormone therapy includes treatments such as tamoxifen and aromatase inhibitors, which are given to women with oestrogen receptor positive breast cancers. They work by preventing oestrogen from stimulating the breast cancer cells to grow, and so reduce the risk of breast cancer coming back after surgical treatment.

Tamoxifen has been shown to reduce recurrence and mortality risk in both premenopausal and postmenopausal women. Meanwhile, aromatase inhibitors are specifically used in women who have gone through the menopause and who are no longer producing oestrogen from their ovaries. These drugs prevent a small amount of oestrogen from being made by fat cells in the body.

Adjuvant hormone therapy is usually recommended for at least five years after surgery in women with oestrogen receptor positive breast cancers.

What did the research involve?

The women in this study were Tayside residents with a hospital discharge or cancer registry record for breast cancer dated between January 1993 and December 2008. Prescribing records, cancer audit and General Registrar’s Office death certificates were obtained for all the women in the study.

The researchers extracted information on the date and the woman’s age at diagnosis, the time between diagnosis and treatment, and the characteristics of the cancer.

The researchers also used each woman’s postcode to estimate the likelihood of them living in poverty (deprivation index) and determined whether each woman had other medical illnesses using hospital and prescribing records.

Prescribing records for tamoxifen and aromatase inhibitors were examined. For each woman the researchers looked at adherence to treatment up to the recommended five years, based on the total days covered by prescriptions and their duration of use.

Women who took hormone treatment for less than 80% of the five years were described as having low adherence.

The main cancer outcomes examined were:

• death from any cause (all-cause mortality)
• breast cancer deaths
• recurrence of breast cancer

What were the basic results?

The researchers identified 3,361 women who started hormone treatment after surgery for breast cancer, 85% of whom started on tamoxifen and 15% on aromatase inhibitors. These women were followed up for 4.37 years on average. Of these 3,361 women who received hormone treatment, 36% (1,194) died during the study period.

Overall adherence to hormone treatment was high, but declined with each year after surgery. Average adherence was:

• 90% in year one
• 82% in year two
• 77% in year three
• 59% in year four

By year five only 51% were still receiving prescriptions for hormone treatment.

When women with high adherence (those who received prescriptions for at least 80% of the five-year period after surgery) were compared with those with low adherence (less than 80%), one-third of the 2,785 women with high adherence died from any cause during follow-up compared with 46% of the 576 women with low adherence. After adjustment for other factors associated with mortality (for example age and tumour stage) the researchers calculated that women with low adherence had a 20% increased risk of dying from any cause compared with women with high adherence (hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.03 to 1.40).

However, interestingly, there was no significant difference in risk of dying specifically from breast cancer between women with high and low adherence, the only difference was in all-cause mortality.

A similar pattern was seen in the risk of breast cancer recurrence – with no significant difference between groups.

The researchers found that women who had good adherence (at least 80%) for three years or less were at increased risk of death from any cause, death due to breast cancer and recurrence compared with women who had good adherence for the total five years. This suggests that the longer a woman is adherent, the less her risk of all-cause and breast-cancer-specific mortality and recurrence.

How did the researchers interpret the results?

The researchers conclude that low adherence to hormone therapy after surgery increases the risk of dying from any cause.

Conclusion

This is a valuable study that looked at a large body of data on the treatment of breast cancer in women in the Tayside region of Scotland over a 15-year period.

Overall, it found that 90% of women who were prescribed hormone treatment to take after surgery (tamoxifen or aromatase inhibitors) took the prescribed drugs during the first year, but adherence gradually declined after this. Only 50% of women were taking hormone treatment by year five – five years being the recommended treatment duration for hormone therapy.

Women who adhered to treatment for less than 80% of the recommended five-year period had 20% increased risk of dying from any cause compared with women who had higher adherence (taking treatment for more than 80% of the five-year period). This was even after adjustment for other factors significantly associated with risk of death (for example age and tumour stage).

Interestingly, adherence had no overall effect on risk of dying specifically from breast cancer, or on risk of breast cancer recurrence.

However, the number of years of good adherence did. Women who had good adherence for three years or less were at increased risk of death from any cause, death from breast cancer and recurrence compared with women who had good adherence for at least five years.

It is not known whether the same results would be seen elsewhere outside of this Scottish region, though the researchers do say that other studies have shown similarly high rates of discontinuation (up to 50%) over the course of hormone treatment. 

Another recognised limitation of the study is that it relies on prescription data to examine adherence to medication, and this may include some inaccuracy. The researchers did not directly ask each woman how long she took hormone therapy for, nor whether she took all drugs that they identified a prescription for.

Overall, this study supports current treatment recommendations. For women with oestrogen receptor positive breast cancer, hormone therapy after surgery is usually recommended for a five-year period.

If you are having problems with side effects speak to the doctor in charge of your care. There may be additional treatment options available that can help.