Ovarian Suppression Plus Tamoxifen Reduces Recurrence Risk Better Than Tamoxifen Alone, but Causes More Severe Side Effects Initially

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After surgery, women diagnosed with early-stage, hormone-receptor-positive breast cancer usually take hormonal therapy medicine to reduce the risk of the cancer coming back (recurrence). Hormonal therapy given after surgery is called adjuvant hormonal therapy.

Hormonal therapy medicines work in two ways:

  • by lowering the amount of estrogen in the body
  • by blocking the action of estrogen on breast cancer cells

There are several types of hormonal therapy medicines. Tamoxifen, a selective estrogen receptor modulator (SERM), is one of the most well-known. Tamoxifen can be used to treat both premenopausal and postmenopausal women. The aromatase inhibitors:

  • Arimidex (chemical name: anastrozole)
  • Aromasin (chemical name: exemestane)
  • Femara (chemical name: letrozole)

have been shown to be more effective at reducing recurrence risk in postmenopausal women and are now used more often than tamoxifen to treat women who’ve gone through menopause.

Right now, aromatase inhibitors aren’t commonly used to reduce recurrence risk in premenopausal women. But because they’re so much more effective in postmenopausal women, researchers wondered if there were a way to successfully treat premenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer with an aromatase inhibitor. Researchers also wondered if ovarian suppression would make tamoxifen more effective in reducing recurrence risk.

The results of the SOFT (Suppression of Ovarian Function Trial) study found that tamoxifen plus ovarian suppression reduces recurrence risk more than tamoxifen alone for premenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer. The results also found that Aromasin plus ovarian suppression reduced recurrence risk even more for this group of women.

In the latest analysis from the SOFT study, the researchers looked at differences in side effects caused by tamoxifen and tamoxifen plus ovarian suppression. The side effects caused by Aromasin plus ovarian suppression were not included in this analysis. The results suggest that ovarian suppression plus tamoxifen caused more side effects and sexual problems -- mainly in the first 2 years of treatment -- compared to tamoxifen alone.

The research was published online on March 28, 2016 by the Journal of Clinical Oncology. Read the abstract of “Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial.”

In the SOFT study, 3,066 premenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer were randomly assigned to get one of three treatments:

  • tamoxifen for 5 years
  • tamoxifen for 5 years plus ovarian suppression with either 5 years of Trelstar (chemical name: triptorelin), surgical removal of the ovaries, or ovarian radiation
  • Aromasin for 5 years plus ovarian suppression with either 5 years of Trelstar, surgical removal of the ovaries, or ovarian radiation

About 47% of the women in the study hadn’t received chemotherapy before, and about 53% had received chemotherapy but were still premenopausal. In other words, their ovaries were still functioning after chemotherapy.

The women in the study completed a quality of life questionnaire at the beginning of the study, before they received any treatments, then every 6 months for 2 years, and then every year for the next 4 years. The questionnaire asked about many health topics, including:

  • physical well-being
  • mood
  • ability to cope with problems
  • hot flashes
  • sexual problems/lack of interest in sex
  • vaginal dryness
  • vaginal discharge
  • sleep problems
  • weight gain

In total, 1,722 women who were treated with either tamoxifen alone or tamoxifen plus ovarian suppression were included in the quality of life analysis. The characteristics of the women in the analysis were:

  • half were younger than 43 years old and half were older
  • 36% were diagnosed with node-positive disease
  • 55% had received chemotherapy before

The two treatment groups had similar quality of life scores at the beginning of the study.

Compared to women treated with tamoxifen alone, women treated with tamoxifen plus ovarian suppression:

  • were more affected by hot flashes 6 months and 2 years after treatment started; 5 years after treatment started this difference had evened out because hot flashes eased a bit in women treated with tamoxifen plus ovarian suppression and got slightly worse in women treated with tamoxifen alone
  • had less interest in sex and more difficulty becoming aroused the entire time they were being treated
  • had more vaginal dryness the entire time they were being treated; women treated with tamoxifen alone had more vaginal discharge and vaginal itching/irritation
  • had more sleep problems 6 months after treatment started; after this time, the differences evened out

These differences were less apparent in women who had been treated with chemotherapy before joining the study.

Women treated with tamoxifen alone had more bone and joint pain compared to women treated with tamoxifen plus ovarian suppression.

The researchers reported that, overall, most of the differences in side effects between the treatment groups eased after 2 years of treatment and were hard to detect after 5 years of treatment. It’s likely that this was partially due to more of the women becoming menopausal during that time. Still, women treated with tamoxifen plus ovarian suppression did have more frequent and more severe side effects, especially hot flashes and sexual problems, the first 2 years they were being treated.

If you’re a premenopausal woman diagnosed with early-stage, hormone-receptor-positive breast cancer that has a high risk of recurrence, you might want to talk to your doctor about this study and ask if tamoxifen plus ovarian suppression is a good option for your unique situation.

While the side effects of hormonal therapy can be very severe for some women, they’re overshadowed by the reality that hormone-receptor-positive breast cancer can come back. Hormonal therapy after surgery reduces that risk. If side effects are a major problem for you, talk to your doctor about ways to manage them. Studies have shown that exercise and acupuncture may reduce hormonal therapy side effects. Visit the Breastcancer.org Staying on Track With Treatment pages to learn more about how to ease side effects.



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