Clinical trial NCT03373708: Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer
Official title: Prospective Randomized Controlled Study on the Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
Chemotherapy
Endocrine Breast Diseases
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2017-12-14
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 5 years
Secondary outcomes:
measure: Expression of female hormone levels
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Zhiyong Yu, PhD
role: STUDY_CHAIR
affiliation: Shandong Cancer Hospital and Institute
name: Zhaoyun Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: