SOFT / TEXT (BIG 2-02 / BIG 3-02)

Intro text: 

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 already provided practice-changing results, giving doctors a new post-operative treatment option 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.

See other publications related to SOFT and TEXT. 

Several substudies are being conducted with the ultimate goal to further optimise the treatment of young women with hormone-sensitive breast cancer. Read more on IBCSG’s website

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:

  • Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer - Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Láng I, Gómez HL, Tondini C, Ciruelos E, Burstein HJ, Bonnefoi HR, Bellet M, Martino S, Geyer CE Jr, Goetz MP, Stearns V, Pinotti G, Puglisi F, Spazzapan S, Climent MA, Pavesi L, Ruhstaller T, Davidson NE, Coleman R, Debled M, Buchholz S, Ingle JN, Winer EP, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT and TEXT Investigators and the International Breast Cancer Study Group. N Engl J Med. 2018 Jun 4.  doi: 10.1056/NEJMoa1803164.
     
  • Adjuvant ovarian suppression in premenopausal breast cancer- Francis PA*, Regan MM*, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer Jr CE, Walley BA, Coleman RC, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD for the SOFT investigators and the International Breast Cancer Study Group. *Co-first authors. N Engl J Med. 2015 Jan 29;372(5):436-46.
     
  • Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. - Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T,Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; the TEXT and SOFT Investigators and the International Breast Cancer Study Group. N Engl J Med 371:107-118, 2014.

Other publications related to SOFT and TEXT 

Pfizer and Ipsen provided the drugs and funding for this study, which was run according to BIG’s Principles of Research Conduct.

SOFT ClinicalTrials.gov identifier: NCT00066690

TEXT ClinicalTrials.gov identifier: NCT00066703