Ovarian Suppression After Surgery Causes More Severe Hot Flashes, Night Sweats in Younger Women

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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. In the early 2000s, the aromatase inhibitors:

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

were 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.

In 2014, two studies, the TEXT (Tamoxifen and Exemestane Trial) and the SOFT (Suppression of Ovarian Function Trial) studies, found that the aromatase inhibitor Aromasin on top of ovarian suppression reduces recurrence risk more than tamoxifen in premenopausal women diagnosed with early-stage, hormone-receptor-positive, HER2-negative disease. So younger premenopausal women could take Aromasin as their hormonal therapy as long as their ovarian function also was suppressed.

Still, tamoxifen, the aromatase inhibitors, and ovarian suppression can cause troubling side effects, including hot flashes and muscle and joint pain. Other research suggests that many women -- from about 25% to 40% -- who are prescribed hormonal therapy to reduce recurrence risk after breast cancer surgery either don’t start taking the medicine or stop taking it early, in many cases because of side effects.

In this analysis of data from the TEXT and SOFT studies, the researchers looked at the benefits and side effects of the hormonal therapies used in the studies and their effects on young women’s quality of life. The researchers also looked to see how many young women stuck to their treatment plans.

The research was published online on June 27, 2017 by the Journal of Clinical Oncology. Read the abstract of “Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials.”

Both the TEXT and the SOFT studies wanted to know if aromatase inhibitors could reduce the risk of recurrence better than tamoxifen in premenopausal women who were diagnosed with early-stage, hormone-receptor-positive breast cancer.

In the TEXT study, Trelstar (chemical name: triptorelin) was used to suppress the ovaries. The women were randomly assigned to receive either:

  • Aromasin plus Trelstar for 5 years
  • tamoxifen plus Trelstar for 5 years

About 44% of the women in the TEXT study also were treated with chemotherapy, which started the same time as Trelstar.

In the SOFT study, the women were randomly assigned to receive one of three treatments:

  • tamoxifen for 5 years
  • tamoxifen for 5 years plus ovarian suppression with either 5 years of Trelstar, 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 SOFT 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.

In this latest analysis, the researchers looked at women from both studies who were age 35 or younger and had been diagnosed with hormone-receptor-positive, HER2-negative breast cancer.

For the TEXT study, information from 145 women was analyzed. Five-year recurrence-free rates were:

  • 79.2% for women treated with tamoxifen plus Trelstar
  • 81.6% for women treated with Aromasin plus Trelstar

For the SOFT study, information from 240 women was analyzed. Five-year recurrence-free rates were:

  • 67.1% for women treated with tamoxifen alone
  • 75.9% for women treated with tamoxifen plus ovarian suppression
  • 83.2% for women treated with Aromasin plus ovarian suppression

So Aromasin plus ovarian suppression reduced recurrence risk the most for women younger than 35 in both studies.

The side effects that affected quality of life the most were hot flashes and night sweats. These symptoms dramatically increased for the first 6 months of the studies. After 6 months, hot flashes and night sweats:

  • improved somewhat in women treated with ovarian suppression
  • got worse in women treated with tamoxifen alone

Other troubling side effects that women treated with ovarian suppression experienced were:

  • loss of interest in sex
  • problems becoming sexually aroused

Women treated with Aromasin plus ovarian suppression also reported significant vaginal dryness.

The vaginal dryness and loss of interest in sex side effects didn’t get better over time.

Women treated with Aromasin and ovarian suppression also reported more bone/joint pain 6 months after the studies started; this pain leveled out after 6 months.

Women treated with tamoxifen and ovarian suppression as well as women treated with tamoxifen alone also had bone/joint pain. For these women, the pain took longer to develop, but reached the same level as that experienced by women treated with Aromasin after about 2 years.

While these side effects and their severity were similar to those experienced by women of all ages in the two studies, there was one notable difference. Compared to women age 35 and older, women younger than 35 had more and more severe night sweats and hot flashes.

Overall, 19.8% of women younger than 35 stopped taking hormonal therapy medicine early. This non-compliance rate was higher in these younger women than it was in women age 35 and older. For women younger than 35, the percentage of women who stopped taking hormonal therapy by study year was:

  • 11% after 1 year
  • 17% after 2 years
  • 23% after 3 years
  • 25% after 4 years

For women 35 and older, the percentage of women who stopped taking hormonal therapy by study year was:

  • 9% after 1 year
  • 14% after 2 years
  • 18% after 3 years
  • 21% after 4 years

“Benefit from the addition of [ovarian suppression] must be weighed against toxicity,” the researchers wrote in their conclusion. “Several observational studies have reported that younger age is associated with lower rates of treatment compliance with endocrine therapy, possibly suggesting the level of toxicity (e.g., sexual toxicity) is less acceptable to women younger than 35 years.”

If you’re a premenopausal woman who has been diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence and want to do everything you can to reduce that recurrence risk, you may want to talk to your doctor about this study.

If you’re willing to take medicine to suppress the function of your ovaries, you may be able to take Aromasin instead of tamoxifen for your hormonal therapy treatment after surgery.

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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