Breast cancer
Hormone-receptor-positive advanced breast cancer becomes resistant to endocrine therapy partly by activating mTOR; adding the rapalog everolimus re-sensitizes it (BOLERO-2).
A cancer where a rapalog is used with hormone therapy.
BOLERO-2: progression-free survival benefit, no clear overall-survival benefit, meaningful toxicity – a resistance-delaying rather than curative effect.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| H | Human study | 2 |
| A | Animal model | 1 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | H | EVERolimus effectiveness after proGREssion on ENdocrine therapy plus CDK4/6 inhibitor for ER-positive/HER2-negative advanced breast cancer: EVERGREEN study MAR2026 Everolimus added to endocrine therapy provided modest but statistically significant PFS benefit (5.0 vs 4.3 months; HR 0.68) in ER+/HER2- advanced breast cancer post-CDK4/6 inhibitor progression, without demonstrable OS benefit, supporting selective use. Retrospective and non-randomised, so treatment-selection bias cannot be excluded. |
| 2012 | H | Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (BOLERO-2) BAS2012 A phase 3 RCT (n=724) proving mTOR matters in a common cancer. When hormone-therapy stops working in breast cancer, it's partly because mTOR switches on. Adding everolimus more than doubled progression-free survival (10.6 vs 4.1 months by central review) - leading to FDA approval. Main toxicity was stomatitis. |
| 2023 | A | A bi-steric mTORC1-selective inhibitor overcomes drug resistance in breast cancer MEN2023 RMC-6272, a bi-steric molecule with >25-fold selectivity for mTORC1 over mTORC2, completely suppresses mTORC1 (hitting the rapamycin-resistant substrate 4E-BP1) and overcomes hormone- and CDK4/6-inhibitor resistance in breast cancer cell lines and PDX -- the preclinical basis for the RMC-5552 selective-inhibitor clinical program. |