A Trial of Neoadjuvant Everolimus Plus Letrozole Versus FEC in Women With ER-positive, HER2-negative Breast Cancer

This open, randomized pilot feasibility trial is to evaluate the feasibility and effect of neoadjuvant everolimus plus letrozole versus neoadjuvant fluorouracil, epirubicin plus cyclophosphamide (FEC) in treating postmenopausal women with ER-positive, HER2-negative breast cancer. Forty postmenopausal stage M0, ER-positive, HER2-negative invasive breast cancer women who had a primary tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging were randomly (1:1) enrolled to receive neoadjuvant everolimus plus letrozole for 18 weeks or neoadjuvant FEC for 6 cycles before surgery. The primary objective is to determine the feasibility of neoadjuvant everolimus plus letrozole in postmenopausal patients with ER-positive, HER2-negative breast cancer. Secondary aims are to compare the ultrasound response rate, pathological complete response (pCR) rate, breast-conserving surgery rate, toxicities, and changes in the percentages or counts of peripheral blood CD4+ T cells, CD8+ T cells, tumor-specific CTLs, T helper cells (Th), regulatory T cells (Treg), and NK cells and changes in tumor Ki67 index (pre- versus post- neoadjuvant therapy).

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* The patients signed the written informed consent
* The patients present with non-metastatic unilateral invasive ER-positive, HER2-negative breast cancer with a primary breast tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging.
* Postmenopausal women with age less than 70 years old.
* The patients have no history of hormone therapy, chemotherapy, breast cancer surgery and radiotherapy.
* The patients have normal cardiac functions by echocardiography.
* The patients' ECOG scores are ≤2.
* The patients can swallow pills.
* The results of patients' blood tests are as follows:

  * Hb≥90g/L;
  * WBC≥4E+9/L;
  * Plt≥100E+9/L;
  * Neutrophils≥1.5E+9/L;
  * ALT and AST ≤ triple of normal upper limit;
  * TBIL ≤ 1.5 times of normal upper limit;
  * Creatinine ≤ 1.5 times of normal upper limit.

Exclusion Criteria:

* The patients have other cancers at the same time or have the history of other cancers except controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix uterus;
* The patients have active infections that were not suitable for chemotherapy;
* The patients have severe non-cancerous diseases.
* The patients have bilateral breast cancers or multifocal breast cancers or inflammatory breast cancers.
* The patients have a history of previous treatment with mTOR inhibitors.
* The patients are undergoing current administration of anti-cancer therapies, or are attending other clinical trials.
* The patients are in some special conditions that they cannot understand the written informed consent, such as they are demented or hawkish.
* The patients have allergic history or contraindication of any of the interventional drugs.

• DERIVEDWu W, Chen J, Deng H, Jin L, He Z, Rao N, Nie Y, Yao Y, Yang Y, Su F, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: a randomized pilot trial. BMC Cancer. 2021 Jul 27;21(1):862. doi: 10.1186/s12885-021-08612-y. PMID 34315439
• DERIVEDWu W, Deng H, Rao N, You N, Yang Y, Cao M, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for a randomized pilot trial. Trials. 2017 Oct 25;18(1):497. doi: 10.1186/s13063-017-2228-5. PMID 29070044