SOFT/TEXT: What the Breast Cancer Trial Found

Two linked trials, one question

Most breast cancer is hormone receptor positive, meaning the cancer cells carry receptors that estrogen switches on. Removing the fuel is a large part of treatment.

After menopause the ovaries have already stopped producing estrogen, and drugs called aromatase inhibitors mop up the small amount made elsewhere. Before menopause the ovaries are still running, so the standard drug has long been tamoxifen, which blocks the receptor rather than lowering estrogen.

The open question was whether to shut the ovaries down too — with a monthly injection, surgery, or radiation — and whether doing so would let an aromatase inhibitor be used instead of tamoxifen.

SOFT and TEXT were designed together to answer that. This page reports SOFT's own analysis and the combined exemestane analysis from both trials.

Trial at a glance

Field	Detail
Trials	SOFT and TEXT
Registry number (SOFT)	NCT00066690
Phase	3, randomized
Participants in SOFT	3,066 premenopausal women
Participants in the combined exemestane analysis	4,690
Population	Premenopausal women with hormone-receptor-positive early breast cancer
SOFT arms	Tamoxifen alone; tamoxifen plus ovarian suppression; exemestane plus ovarian suppression
Main measure	Disease-free survival over 5 years

In SOFT, 46.7 percent of participants had not had chemotherapy. The other 53.3 percent had, and remained premenopausal afterward. That split turns out to be the whole story.

The main comparison did not reach significance

SOFT's primary test was tamoxifen plus ovarian suppression against tamoxifen alone.

After a median follow-up of 67 months, five-year disease-free survival was 86.6 percent with ovarian suppression added, against 84.7 percent without. The hazard ratio was 0.83, with a 95 percent confidence interval of 0.66 to 1.04 and P=0.10.

That confidence interval crosses 1.0. The trial did not demonstrate a benefit in the population as a whole. Adjusting for other prognostic factors nudged the hazard ratio to 0.78, with an interval of 0.62 to 0.98, but that was a secondary analysis rather than the primary test.

A negative primary result is not a failed trial. It is an answer.

Where the benefit actually was

Most recurrences happened in women who had already needed chemotherapy — that is, those whose cancers were judged risky enough to warrant it, and who stayed premenopausal afterward.

In that group, freedom from breast cancer at five years was 82.5 percent with tamoxifen plus ovarian suppression, against 78.0 percent with tamoxifen alone. The hazard ratio was 0.78, with an interval of 0.60 to 1.02.

Exemestane plus ovarian suppression did better still in the same group: 85.7 percent free of breast cancer, with a hazard ratio of 0.65 against tamoxifen alone and an interval of 0.49 to 0.87.

The combined SOFT and TEXT analysis, covering 4,690 women, sharpened that. After a median 68 months, five-year disease-free survival was 91.1 percent with exemestane plus ovarian suppression, against 87.3 percent with tamoxifen plus ovarian suppression. The hazard ratio was 0.72, interval 0.60 to 0.85, P<0.001.

Overall survival, though, did not differ. With 194 deaths across 4.1 percent of participants, the hazard ratio for death was 1.14, interval 0.86 to 1.51, P=0.37. Grade 3 or 4 adverse events were reported for 30.6 percent of the exemestane group.

What changed in practice

These trials did not establish that everyone should have ovarian suppression. They established who should be offered it.

For a premenopausal woman at low enough risk that chemotherapy was never on the table, tamoxifen alone remained reasonable. For a younger woman at higher risk who had chemotherapy and whose periods returned, adding ovarian suppression helped, and switching from tamoxifen to exemestane helped more.

That is a risk-stratified decision, taken case by case. Our page on breast cancer covers the receptor tests that feed into it.

What to raise at an appointment

If you are premenopausal with hormone-receptor-positive breast cancer, these are the questions this evidence generates:

• Where does my recurrence risk sit, and what was that estimate based on?
• Did I have chemotherapy, and are my periods still occurring?
• If ovarian suppression is offered, is it by monthly injection, surgery, or radiation, and is it reversible?
• What would suppression mean for bone density, joint pain, mood, sexual function, and fertility?
• If I take an aromatase inhibitor, how will my bone health be monitored?

What this study cannot tell you

• The primary comparison did not reach statistical significance. Any claim that SOFT proved ovarian suppression works for everyone misreads it.
• Disease-free survival is not overall survival. The combined analysis found no survival difference at that follow-up.
• Five-year results in hormone-receptor-positive breast cancer are early. Recurrences in this disease occur well beyond a decade.
• Subgroup findings, including the chemotherapy-treated group, are less reliable than a primary result and were not the trial's main test.
• Ovarian suppression carries real costs: menopausal symptoms, bone loss, and effects on fertility that matter enormously to younger women.
• SEER, the federal cancer surveillance program, records five-year relative survival of 91.9 percent for female breast cancer overall. That is a group average from people diagnosed years ago and describes populations, not individuals.

Sources

• N Engl J Med 2015: Adjuvant ovarian suppression in premenopausal breast cancer (SOFT), PMID 25495490 — record retrieved via NCBI eutils
• N Engl J Med 2014: Adjuvant exemestane with ovarian suppression in premenopausal breast cancer (SOFT and TEXT combined), PMID 24881463 — record retrieved via NCBI eutils
• ClinicalTrials.gov API v2 record for NCT00066690
• NCI SEER Cancer Stat Facts: Female Breast Cancer

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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