BIG 2-02 / BIG 3-02

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Suppression of Ovarian Function (SOFT) with either tamoxifen or exemestane compared with tamoxifen alone in treating premenopausal women with hormone-responsive breast cancer

Triptorelin with either EXemestane or Tamoxifen in treating premenopausal women with hormone-responsive breast cancer (TEXT)

SOFT and TEXT are phase III clinical trials developed in parallel to test the optimal post-operative (i.e. adjuvant) endocrine treatment in premenopausal women with hormone-sensitive early breast cancer.

In particular, SOFT has been evaluating the efficacy of adding ovarian function suppression (OFS) to the standard endocrine treatment (tamoxifen) or to an aromatase inhibitor (exemestane), compared to tamoxifen alone, in reducing the risk of cancer recurrence in this group of patients.

TEXT compares treatment with exemestane plus OFS to tamoxifen plus OFS.

Both trials also aim to measure the side-effects and quality of life of patients with the different treatments.

Young premenopausal women with hormone-sensitive breast cancer may have a high risk of having the cancer come back after surgery, since the oestrogen produced by the ovaries can stimulate the growth and development of cancer cells.

Tamoxifen, a drug that blocks primarily the growth of cancer cells by preventing oestrogen from attaching to the cancer cell receptor, has been the standard hormonal treatment after surgery in this patient population.

Ovarian function suppression (OFS) has also been used for a long time as breast cancer treatment for these patients. However, the benefit of combining OFS to a hormonal therapy was uncertain.

Exemestane is an aromatase inhibitor that can also slow or stop the growth of hormone-sensitive tumours by blocking an enzyme that converts other hormones into oestrogen. Its benefits had already been demonstrated in postmenopausal women with hormone-sensitive breast cancer.

SOFT and TEXT together have delivered practice-changing results that persist over time, providing important post-operative treatment options for young women with hormone-sensitive early breast cancer who may have a higher risk of cancer recurrence after surgery.

Results showed that adding ovarian function suppression (OFS) to the standard hormonal treatment (tamoxifen) reduced the risk of developing further breast cancer by 28 % compared to tamoxifen alone in this group of patients.

Furthermore, the two studies demonstrated that even better results were achieved (risk of recurrence reduced by 34 %) when combining OFS with exemestane, compared to OFS combined with tamoxifen.

After five years, 92.8% of the patients treated with exemestane and OFS were breast cancer-free, compared with 88.8% for the women treated with tamoxifen and OFS.

SOFT and TEXT also found that premenopausal women who presented a lower risk of cancer recurrence, and whose post-operative treatment included only tamoxifen without chemotherapy, did not benefit from adding OFS to their treatment.

The combined first results of SOFT and TEXT were published in 2014 in the New England Journal of Medicine and were supported by a 5-year analysis presented at the 2017 San Antonio Breast Cancer Symposium (SABCS).

The most recent results presented at the 2021 SABCS, with patients having been followed-up for an average of 12.5 years since starting treatment, show a persistent long-term reduction of risk of distant recurrence when OFS is added to tamoxifen or exemestane, with the greatest reduction found in combination with exemestane. The updated results also demonstrate a reduction in death with both combinations, although the reduction was higher with exemestane.

SOFT en TEXT hebben resultaten opgeleverd die de gangbare praktijken hebben veranderd die vandaag nog steeds gelden. Ze bieden belangrijke postoperatieve behandelingsmogelijkheden voor jonge vrouwen met hormoongevoelige borstkanker in een vroeg stadium, die na de operatie mogelijk een hoger risico op herval lopen.

Several substudies are being conducted with the ultimate goal to further optimise the treatment of young women with hormone-sensitive breast cancer.

SOFT and TEXT are complementary trials, conducted over the same period of time and on the same patient population.

Patients were randomly assigned in the following treatment groups:

– tamoxifen alone

– tamoxifen combined with ovarian function suppression (OFS)

– exemestane combined with OFS

For most patients, OFS was achieved by injecting triptorelin, a drug that momentarily blocks the ovarian function and, as a result, reduces the production of oestrogen.

Patients considered at high risk of cancer recurrence by their doctor (usually younger, =<35 years), also received chemotherapy after surgery.

Patients considered at lower risk of cancer recurrence received tamoxifen alone, chemotherapy being considered as not necessary. Those women were usually older (~46 years).

Patients were treated for 5 years and will continue to be followed for life to assess long-term prognosis, treatment tolerability and side-effects.

In total SOFT and TEXT enrolled 5,738 women with hormone-sensitive early breast cancer.

SOFT and TEXT are coordinated by the International Breast Cancer Study Group (IBCSG), which is also the study sponsor, under the Breast International Group umbrella, and in collaboration with the North American Breast Cancer Group (NABCG) and the National Cancer Institute (NCI).

Recruitment of patients started in November 2003 and completed in April 2011.

510 hospitals and cancer centres in 27 countries are participating in these trials.

Main publications:

Grant support from Breast Cancer Research Foundation, Cancer Research CH, Pfizer, Ipsen, Debiopharm, TerSera Therapeutics, US NCI, IBCSG and many participating collaborative academic groups, as well as various charities. Pfizer and Ipsen provided the drugs for these studies, which were run according to BIG’s Principles of Research Conduct.

SOFT identifier: NCT00066690

TEXT identifier: NCT00066703

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