Multi-institutional Study to Increase Breast Conserving Surgery (BCS) Rate With Personalized Neoadjuvant Strategy in ER Positive and HER2 Negative Breast Cancer Patients for Whom BCS is Not Feasible
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Conversion Rate
研究概览
简要总结
In ER+ and HER2- breast cancer(BC) patients for whom BCS is not feasible, we investigate the rate of BCS can be increased while decreasing unnecessary chemotherapy thru selective neoadjuvant chemotherapy or neoadjuvant endocrine therapy using tools of nodal status, Ki-67, and multigene assay(Mammaprint)
详细描述
In patients with resectable BC, the neoadjuvant chemotherapy is recognized as one of the standard therapy in order to control and prevent the micrometastasis.
Conducting neoadjuvant chemotherapy can lead to increased numbers of BCS compared with adjuvant chemotherapy and the prognosis of BC patients is known to be improved when there is pathological complete response (pCR) after neoadjuvant chemotherapy compared with no pCR.
The effect of neoadjuvant chemotherapy is different in breast cancer subtypes. The quasi-pCR in HR- HER2+ BC is reported as 67% while 37% and 13% in triple negative and HR+ HER2- BC, respectively and it indicates that neoadjuvant chemotherapy has only limited effect in HR+ BC and the declined quality of life and the fecundity loss due to chemotherapy is a serious socioeconomic loss, especially in young patients.
According to the SOFT trial, for high risk, pre-menopausal women, use of exmestane (AI, Aromatase Inhibitors) and ovarian suppression as adjuvant systemic therapy did improve the PFD compared with the use of tamoxifen and ovarian suppression.
Neoadjuvant hormonal therapy as well as neoadjuvant chemotherapy has benefits in making inoperable BC to operable BC and improving the possibility of BCS by reducing the tumor size with complete response or partial response. Although these neoadjuvant systemic therapies have an ultimate objective to reduce the recurrence rate and improve the survival rate, the overall survival and disease-free survival has been reported similar to adjuvant systemic therapies. The clinical response rate of neoadjuvant hormonal therapy ranged from 13.5% to 100%, the radiologic response rate by ultrasound ranged from 20% to 91.7%, and these are statistically similar to the response rate of the neoadjuvant chemotherapy in ER+ patients. Most studies where letrozole was tested among AIs showed that letrozole has a similar or a little better effect on clinical or radiological response rate over tamoxifen and there were statistically more patients who became operable or eligible for BCS after neoadjuvant chemotherapy. Comparison studies among AIs showed that the response rates have been best achieved in letrozole over anastrozole and exemestane and the BCS rate was lowest in letrozole without statistical significance. According to the standard treatment guideline suggesting the selective use of ovarian suppression along with tamoxifen in HR+, premenopausal patients, a study investigated the combined treatment of letrozole with reversible ovarian ablation using goserelin (luteinizing hormone-releasing hormone: LHRH). The results showed that the response rate of the combination treatment of goserelin and anastrozole for 24 weeks as neoadjuvant hormonal therapy was statistically superior to goserelin and tamoxifen in premenopausal BC patients and this was not observed in the adjuvant setting. The most commonly used agents in BC are goserelin and leuprorelin(Leuplin) and their mechanism of action is to desensitize the hypothalamus and suppress the ovarian function by reducing the secretion of LH and FSH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histopathologically and immunohistochemically confirmed ER+ and HER2- BC patients
- •Stage I-IIIA BC patients with detectable tumor sizes
- •BC patients for whom BCS is not feasible due to tumor sizes or locations (two surgeons at each institution evaluate the infeasibility of BCS)
- •Patients without distant metastasis which were identified pathologically or radiologically
- •Female patients ≥ 19 years
- •Diagnosis of menopause is defined as no menstruation for 1-year or both ovaries removed surgically
- •Patients with adequate bone marrow function
- •Hemoglobin 10 g/dL, ANC 1,500/mm3, Plt 100,000/mm3
- •Patients with adequate kidney function
- •serum Cr ≤ 1.5 mg/dL
- •Patients with adequate liver function
- •Bilirubin: ≤ 1.5 times of upper normal limit
- •AST/ALT: ≤ 1.5 times of upper normal limit
- •Alkaline phosphatase: ≤ 1.5 times of upper normal limit
- •Patients who decided to voluntarily participate in this trial with written informed consent
排除标准
- •History of treatment for ipsilateral BC or breast carcinoma in situ
- •Confirmed distant metastasis of BC
- •History of cancer other than BC
- •Pregnant (positive pregnancy test within a week of enrollment) or breast-feeding patients
- •Uncontrolled severe infection
- •Psychiatric illness or epilepsy
- •Male BC patients
- •Inability to understand and willingness to sign a written informed consent
- •Mammographic extensive microcalcification
- •Multicentral, Bilateral BC
- •History of chemotherapy or endocrine therapy on contralateral BC for the past 2 years
- •Undetectable and unmeasurable primary tumor size
研究组 & 干预措施
Arm I
- MammaPrint high risk :
- Neoadjuvant chemotherapy : Adriamycin/Cyclophosphamide #4 followed by Docetaxel #4
- MammaPrint low risk :
- Premenopausal women : Letrozole 2.5mg PO QD + leuprorelin acetate 3.6mg SQ every 4weeks during 16 weeks (if needed, maximum for 24 weeks)
- Postmenopausal women : Letrozole 2.5mg PO QD during 16 weeks (if needed, maximum for 24 weeks)
干预措施: Leuprorelin acetate (Drug)
Arm I
- MammaPrint high risk :
- Neoadjuvant chemotherapy : Adriamycin/Cyclophosphamide #4 followed by Docetaxel #4
- MammaPrint low risk :
- Premenopausal women : Letrozole 2.5mg PO QD + leuprorelin acetate 3.6mg SQ every 4weeks during 16 weeks (if needed, maximum for 24 weeks)
- Postmenopausal women : Letrozole 2.5mg PO QD during 16 weeks (if needed, maximum for 24 weeks)
干预措施: Letrozole (Drug)
Arm I
- MammaPrint high risk :
- Neoadjuvant chemotherapy : Adriamycin/Cyclophosphamide #4 followed by Docetaxel #4
- MammaPrint low risk :
- Premenopausal women : Letrozole 2.5mg PO QD + leuprorelin acetate 3.6mg SQ every 4weeks during 16 weeks (if needed, maximum for 24 weeks)
- Postmenopausal women : Letrozole 2.5mg PO QD during 16 weeks (if needed, maximum for 24 weeks)
干预措施: MammaPrint (Genetic)
结局指标
主要结局
Conversion Rate
时间窗: 4 months(maximum 6 months)
Evaluate the conversion rate from BCS-ineligible to BCS-eligible patients
次要结局
- Actual Conversion Rate(4 months(maximum 6 months))
- pCR(4 months(maximum 6 months))
- cCR(4 months(maximum 6 months))
- Tumor Size Reduction Rate(4 months(maximum 6 months))
研究者
Wonshik Han
Professor
Seoul National University Hospital