Who Benefits from Ovarian Suppression in Breast Cancer? 12-Year Follow-up Results

Most breast cancers have high levels of oestrogen and/or progesterone receptors in their cells and are called hormone-positive breast cancers. In hormone-positive breast cancer, hormone-suppressing treatments can slow or stop cancer cell growth by reducing or stopping oestrogen and progesterone production. Commonly used oral medicines include tamoxifen, Arimidex and Aromasin. Another way to block the action of female hormones is to suppress ovarian function. Ovarian suppression has therefore become a standard treatment in breast cancer.

Ovarian function can be suppressed by surgically removing the ovaries (bilateral oophorectomy), giving radiotherapy to the ovaries, or giving intramuscular ovarian-suppressing injections monthly/every 3 months.

Ovarian suppression in breast cancer is given in addition to standard hormonal treatment, particularly in premenopausal women. It is especially preferred for patients whose clinical and pathological features indicate a high risk of recurrence.

Duration of Hormonal Treatment in Hormone-Positive Breast Cancer

Adjuvant (postoperative preventive) hormonal treatment lasts at least 5 years, which is the usual preferred duration. For some patients with high-risk features, it may be extended to 1o years. Extended treatment may help some patients because the risk of distant recurrence after 5 years has been shown to continue for more than 20 years in women with breast cancer. However, some patients benefit less, and for some the risks may outweigh the benefits. Oncologists therefore weigh the benefits and risks of extending treatment and make an individual decision. Women with node-positive breast cancer are advised to receive adjuvant hormonal treatment for a total of up to 10 years.

The decision to add ovarian suppression to standard treatment depends on factors such as age, menopausal status, breast cancer risk and other health conditions. Postoperative ovarian suppression is not recommended for every premenopausal woman with early-stage breast cancer; selecting patients who will benefit is important. Which patients benefit from ovarian suppression remains an important question in oncology.

A 12-Year Study

The 12-year results of SOFT, a study designed to answer this question, were published on 9 December 2022 in Journal of Clinical Oncology.

SOFT investigated adding ovarian function-suppressing treatment to hormonal treatment in premenopausal women with hormone-positive breast cancer. In the study, 3,047 patients were randomly assigned to tamoxifen plus ovarian suppression (1,015), exemestane plus ovarian suppression (1,014), or tamoxifen alone (1,018).

Ovarian function suppression was achieved with intramuscular triptorelin injections, surgical removal of the ovaries or their destruction by radiotherapy.

Overall, 85% of patients had hormone-positive, HER2-negative breast cancer.

The primary analysis compared tamoxifen plus ovarian suppression with tamoxifen alone, while comparing exemestane plus ovarian suppression with tamoxifen was a secondary objective.

At 5 years, adding ovarian suppression to tamoxifen showed no benefit. At 8 years, a significant difference in disease-free survival and overall survival was found in the tamoxifen/ovarian suppression group. The current analysis presents results after an average follow-up of 12 years.

Results

Disease-free survival at 12 years was:

• 76.1% with tamoxifen/ovarian suppression
• 79.0% with exemestane/ovarian suppression, and
• 71.9% with tamoxifen alone.

Overall survival at 12 years was:

• 89.0% with tamoxifen/ovarian suppression
• 89.4% with exemestane/ovarian suppression, and
• 86.8% with tamoxifen.

At 12 years, adding ovarian suppression to hormonal treatment provided absolute overall survival benefits in groups with high-risk clinical and pathological features.

Features associated with high risk were:

• Previous neoadjuvant chemotherapy
• Age 35 or younger, and
• Subgroups with high-risk clinical and pathological features, such as grade 3 disease

In conclusion, adding ovarian suppression to postoperative preventive hormonal treatment appears to provide a meaningful benefit, particularly in younger patients, those who received neoadjuvant treatment because their cancer was locally advanced at diagnosis, and those with high-risk clinical and pathological features.