Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer
Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer
Breast cancer is the most common female malignancy in the world, and the leading cause of
 cancer-associated mortalities among women. Hormone receptors (HR) including ER and PR are the
 main prognostic factor for breast cancer patients. Breast cancer subtype was defined by ER,
 PR, HER2 and Ki67 status since the definition of intrinsic subtypes for breast cancer. Breast
 cancer which ER are positive have less aggressive and better long-term prognoses than other
 breast cancer subtype. Luminal B1 was definited as ER Positive, PR positive <20%, or Ki-67
 ≥20% , and HER2-Negative. Although standard therapy to HR positive breast cancer is endocrine
 treatment, evidence reported that Luminal B1 breast cancers with lower PR expression are less
 sensitive to tamoxifen than luminal A breast cancers with higher PR expression, and the
 specific mechanism is not clear. We previously had a clinically analysed, and we found the
 Luminal B1 breast cancer had a significant proportion with 38%. Whether we need standard
 chemotherapy or chemotherapy based intensive endocrine therapy for those patients? In our
 research, we divided the patients with ER positive, PR negative, and HER-2 negative into two
 groups. One groups will be treated with 8 cycles of chemotherapy (EC×4-T×4). The other
 received 4 cycles of chemotherapy (TC×4) then will be given the intensive endocrine therapy
 (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal patients). The
 primary endpoint is to assess disease-free survival (DFS) and overall survival (OS) in
 different regiments, the secondary endpoint is to assess the expression of female hormone
 levels. The correlation of the expression of female hormone levels with the clinical
 outcomes, so that the investigators could optimize adjuvant treatment regiment with luminal
 B1 breast cancer.
The trial is designed to investigative the risk and clinical benefit of chemotherapy and
 intensive endocrine therapy for Luminal B1 early-staged breast cancer. In this trial the
 investigators will randomly assign 200 primary breast cancer patients to receive four cycles
 of epirubicin and cyclophosphamide (EC) followed by four cycles of docetaxel(T), or four
 cycles of docetaxel and cyclophosphamide (TC) followed by intensive endocrine therapy
 (Goserelin acetate+Tamoxifen/Letrozole for young patients) . Patients with HER-2 positive was
 excluded. The patient's conditions will be assessed before, and after every four cycles of
 adjuvant chemotherapy to determine if there is any progression of the disease. The patient's
 conditions will be assessed every three months when they received the intensive endocrine
 therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal
 patients). Patients will be followed up for DFS and OS in different regiments, the secondary
 endpoint is to assess the expression of female hormone levels. The correlation of the
 expression of female hormone levels with the clinical outcomes, so that the investigators
 could optimize adjuvant treatment regiment with luminal B1 breast cancer.
Inclusion Criteria:

 -  All patients were required to give written informed consent.

 -  Patients present with operable breast cancers that were diagnosed by histopathology
 and have no distant metastasis.

 -  Have no history of anti-cancer therapies including chemotherapy, radiation therapy,
 hormone therapy and surgical therapy

 -  Have normal cardiac functions by echocardiography

 -  ECOG scores are ≤ 0-1.

 -  Patients are disposed to practice contraception during the whole trial.

 -  The results of patients' blood tests are as follows:

 Hb ≥ 90 g/L WBC ≥ 3.0×109/L Plt ≥ 100×109/L Neutrophils ≥ 1.5×109/L ALT and AST ≤ 2.5 times
 of normal upper limit. TBIL ≤ 1.5 times of normal upper limit. Creatinine ≤ 1.5 times of
 normal upper limit.

 -  ER+ Her2- early-stage breast cancer

 Exclusion Criteria:

 -  Have other cancers at the same time or have the history of other cancers in recent
 five years, excluding the controlled skin basal cell carcinoma or skin squamous cell
 carcinoma or carcinoma in situ of cervix.

 -  Active infections

 -  Severe non-cancerous diseases.

 -  The patients are undergoing current administration of anti-cancer therapies, or are
 attending some other clinical trails.

 -  Inflammatory breast cancer.

 -  Pregnant or lactational, or patients refuse to practice contraception during the whole
 trial.- Page 5 of 5 -

 -  The patients are in some special conditions that they can't understand the written
 informed consent, such as they are demented or hawkish.

 -  Have allergic history of the chemotherapeutic agents.

 -  Bilateral breast cancers