> Is an Aromatase Inhibitor with Ovarian Suppression Better for Premenopausal Women?

Is an Aromatase Inhibitor with Ovarian Suppression Better for Premenopausal Women?


Treating hormone receptor-positive breast cancer with an aromatase inhibitor, or AI, usually used only in postmenopausal women, significantly reduced breast cancer return in premenopausal women when used with ovarian suppression, according to the preliminary reports of two combined studies.

Risk reduction was compared to using tamoxifen plus ovarian suppression. Tamoxifen is the standard of care for premenopausal women with hormone receptor-positive disease. Postmenopausal women are those who no longer have ovarian functions.

This finding may change physicians’ treatment advice to some premenopausal women. The study was presented at the American Society of Clinical Oncology’s annual meeting in May.

Background and Reason for the Study

AIs and tamoxifen are hormonal medicines that target the estrogen some breast cancers need to grow. They are given to women with hormone-positive breast cancer after surgery. Both medicines lower the risk of disease return, or recurrence.

Estrogen is made in the ovaries as well as elsewhere in the body, such as white fat cells. AIs stop estrogen production in sites other than the ovaries, so AIs are only offered and effective in postmenopausal women. Tamoxifen acts by directly competing with estrogen, so is offered and effective in both premenopausal and postmenopausal women.

The recommendation for premenopausal women has been tamoxifen, given for 5 years and now recommended for up to 10 years. Some also have treatment to lower their estrogen levels through ovarian suppression – medicine, surgery or radiation therapy that further slows or stops their ovaries from producing estrogen.

Almost 10 years ago, researchers began two large clinical trials looking at whether post-surgery AI treatment with ovarian suppression benefitted premenopausal women more than tamoxifen with ovarian suppression.

Study Structure

This study was a combined analysis of parts of the two trials, which included premenopausal women from 27 countries. All had hormone receptor-positive, early-stage breast cancer and either breast removal, mastectomy, or partial removal, lumpectomy. Some received chemotherapy and some were taking trastuzumab, a medicine for HER2-positive disease.

The women were randomly placed in treatment groups using an AI called exemestane (Aromasin) with ovarian suppression or receiving tamoxifen with ovarian suppression. Estrogen production by the ovaries was slowed or stopped through treatment with a hormone-targeting medicine known as triptorelin, surgery or radiation therapy.


There were 4,690 women included in the study, from international and North American centers. They had a median age of 43 years. Almost half – 42.2 percent – had breast cancer in their lymph nodes, increasing risk of recurrence depending on the number of nodes involved, as well as early-stage disease in one or both breasts.

At a median follow-up of 5.7 years, treatment using exemestane with ovarian suppression, compared to tamoxifen with ovarian suppression, significantly improved disease-free survival, or time without cancer, and extended time without a distant return, or metastasis.

The researchers found

  • disease-free survival rate at 5 years was
    • 91.1 percent for the AI with ovarian suppression group
    • 87.3 percent for the tamoxifen with ovarian suppression group
  • a relative reduction, measured by several factors, of 34 percent in risk of breast cancer returning
  • among those who had chemotherapy, avoidance of distant return was 2.6 percentage points higher in those receiving AI with ovarian suppression compared to tamoxifen with ovarian suppression
  • overall survival was more than 95 percent for both groups
    • longer follow-up is needed to see if there is a significant survival difference


The study did not look at the difference between giving hormonal therapy with ovarian suppression versus tamoxifen alone. This will be further evaluated when the SOFT trial reports later this year, taking into account survival data as well as side effects of putting a premenopausal woman in menopause for 5 years. This may lead to major changes in national treatment recommendations.

What This Means for You

If you are premenopausal and have hormone receptor-positive early-stage breast cancer, you may have been advised to take tamoxifen after your primary treatment. Tamoxifen, with or without ovarian suppression, may still be the right hormonal therapy for you. It has been highly beneficial for many women for years.

This study presents another option to discuss with your doctor: using the AI exemestane – instead of tamoxifen – with ovarian suppression. Your individual diagnosis, treatments received and other factors will contribute to making a decision that is right for you.

Pagani, O, Regan, MM, Walley, BA et al. Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer. New England Journal of Medicine, 2014; doi: 10.1056/NEJMoa1404037.