Aromasin Plus Ovarian Suppression Better Than Tamoxifen for Premenopausal Women With Hormone-Receptor-Positive, HER2-Negative Disease With High Recurrence Risk

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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 2005, 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, the results of two studies, the TEXT (Tamoxifen and Exemestane Trial) and the SOFT (Suppression of Ovarian Function Trial) studies, suggested 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.

The researchers who did the studies wanted to know if there were certain premenopausal women who would benefit the most from Aromasin plus ovarian suppression after surgery. So they did another analysis of the data. The results show that premenopausal women diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence benefit the most from Aromasin plus ovarian suppression. Women diagnosed with cancer with an intermediate risk of recurrence got some benefit and women diagnosed with cancer with a low risk of recurrence got minimal benefit.

The study was published online on April 4, 2016 by the Journal of Clinical Oncology. Read the abstract of “Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT 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 of TEXT and SOFT data, the researchers looked at information from 4,891 women diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer.

The researchers calculated the risk of recurrence for each woman, taking into account:

  • the woman’s age
  • the size of the cancer
  • whether cancer was in the lymph nodes or not
  • the grade of the cancer
  • estrogen and progesterone receptor expression levels
  • Ki-67 levels; Ki-67 is a protein in cells that increases as they prepare to divide, so higher levels usually means more aggressive cancer

Then they looked to see how long each woman lived without a recurrence, which they called a breast cancer free interval (BCFI).

Women in the SOFT study who were still premenopausal after chemotherapy treated with Aromasin plus ovarian suppression who had the highest recurrence risk had a 10% to 15% improvement in BCFI compared to women treated with tamoxifen plus ovarian suppression or tamoxifen alone. Women with intermediate recurrence risk had at least a 5% improvement in BCFI.

Women in the SOFT study who didn’t receive chemotherapy had the lowest recurrence risk on average and did well no matter which hormonal therapy they received. So these women didn’t receive any extra benefit if they were treated with Aromasin plus ovarian suppression.

Women in the TEXT study who weren’t treated with chemotherapy and had a low risk of recurrence did well with either Aromasin plus ovarian suppression or tamoxifen plus ovarian suppression.

The results of this analysis are promising for women diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence and suggest that Aromasin plus ovarian suppression offers benefits for them.

Still, tamoxifen, the aromatase inhibitors, and ovarian suppression can cause side effects, including hot flashes and muscle and joint pain. The benefits the treatments offer need to be weighed against any side effects.

The researchers said that for women in the study with the lowest risk of recurrence, any benefit of Aromasin plus ovarian suppression compared to tamoxifen alone might not outweigh the additional side effects. For women with the highest risk of recurrence, it’s likely that the benefit of Aromasin plus ovarian suppression would outweigh any added side effects.

“For women whose recurrence risk was intermediate, the benefit of [Aromasin] plus ovarian suppression over tamoxifen, with or without ovarian suppression, was moderate…requiring a balanced discussion of benefits and adverse effects,” the researchers wrote. “Consideration of preference, tolerance, and cost should also inform the decision-making process.”

Larry Norton, M.D., medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center and a Breastcancer.org Professional Advisory Board member, said in an interview that ovarian suppression plus Aromasin offers women another treatment option.

“There are reasons why someone might not want to take tamoxifen, just as there are reasons why somebody might want to take tamoxifen. Those are going to enable individualized decisions.”

If you’re a premenopausal woman diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence, you may want to talk to your doctor about this study.

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

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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