The aim of SOLE was to compare two different regimens of letrozole – intermittent versus continuous – when given as extended endocrine adjuvant treatment to prevent cancer recurrence in postmenopausal women with hormone receptor-positive, lymph node-positive, early breast cancer, who were breast cancer-free following 4 to 6 years of prior adjuvant endocrine treatment.

In hormone receptor-positive breast cancer, tumour cells require oestrogen to grow. The drug letrozole (an aromatase inhibitor) lowers the amount of oestrogen in the body and consequently helps fight disease progression and/or recurrence.

Nowadays the trend is to extend adjuvant endocrine treatment for women with hormone receptor positive/HER2-negative early-stage breast cancer; in practice, this can mean up to 10 years of continuous therapy.  

In laboratory studies of mice with implanted breast cancer cells that had become resistant to letrozole treatment, the rise in oestrogen levels during treatment breaks re-sensitised the breast cancer cells to letrozole when restarted after the break.

SOLE’s hypothesis was that introducing 3-month treatment-free intervals during the course of 5 years of extended letrozole treatment would reduce the risk of cancer recurrence and thus improve disease-free survival.

The study results were presented at ASCO 2017.

Read the press release dated 05 June 2017

SOLE established that taking planned 3-month treatment breaks during long-term treatment with letrozole does   not improve disease-free survival compared with taking the treatment continuously for 5 years for postmenopausal women with hormone-sensitive, node-positive early breast cancer who have already received 4 to 6 years of adjuvant endocrine therapy.

However, doctors observed improvement with regard to patient-reported symptoms and quality of life (physical well-being, sleep disturbances, hot flushes, etc.) with the intermittent administration.

Patients had completed their first approximately 5 years of endocrine therapy within the 12 months prior to enrolment into SOLE.

They were randomly assigned to extend their endocrine therapy by taking either:

• an additional 5 years of continuous letrozole, or
• 5 years of intermittent letrozole (taken for the first 9 months during years 1 to 4, and then continuously for 12 months in year 5).

To assess long-term prognosis, patients enrolled in SOLE continue to be followed for life after their endocrine treatment.

Postmenopausal women with hormone-sensitive, lymph node-positive breast cancer who were breast cancer-free following 4 to 6 years of prior adjuvant (post-surgical) endocrine therapy.

In total 4,884 patients were enrolled between November 2007 and July 2012 in 22 countries worldwide.

This study is coordinated and sponsored by the International Breast Cancer Study Group (IBCSG) and is conducted under the Breast International Group (BIG) umbrella.

Pharmaceutical partner: Novartis

• Colleoni M, Luo W, Karlsson P et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
  Lancet Oncol. 2018 Jan;19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5.
• Abderrahman B, Jordan VC. Rethinking Extended Adjuvant Antiestrogen Therapy to Increase Survivorship in Breast Cancer. JAMA Oncol. 2018 Jan doi: 10.1001/jamaoncol.2017.3510.

Novartis provides drugs and funding for this study, which is being run according to BIG’s Principles or Research Conduct.

NCT00553410