[Background]
MammaPrint, which analyses 70-gene expressed in breast cancer, can identify low risk patients who may safely forgo chemotherapy and high risk patients who can benefit from chemotherapy.  Recent results from MINDACT trial have proved that 46.2% of HR+ and clinical high risk patients were classified into MammaPrint low risk and they could avoid unnecessary chemotherapy(21). In 2017 San Antonio breast cancer symposium, Dubsky et al. reported the analysis of correlation between neoadjuvant chemotherapy and score of Endopredict(EP) multigene assay in ER+ and HER2- patients treated on ABCSG 34. In neoadjuvant chemotherapy group, reduction of tumor size in patients with low EP score(Endopredict low risk group) was significantly low(NPV 100%). Meanwhile, in neoadjuvant hormonal therapy group, reduction of tumor size in patients with high EP score(Endopredict high risk group) was significantly low(NPV 92%). These results support the evidence that response of neoadjuvant chemotherapy or hormonal therapy can be predicted by the molecular score of tumor and selective treatment can maximize the effect.

[Method]
in this study, patients with MammaPrint test is performed, neoadjuvant chemotherapy is conducted to genomic High Risk patients, and neoadjuvant endocrine therapy is conducted to Low Risk patients.

[Objective]
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

Treatment

Single Arm
1. MammaPrint High Risk group:
Neoadjuvant chemotherapy with AC#4 followed by Docetaxel#4
2. MammaPrint Low Risk group:
	Pre-menopausal patients: Letrozole 2.5mg PO QD+ leuprorelin 3.75mg SQ every 4 weeks during 16weeks(if needed, maximum for 24 weeks)
	Post-menopausal patients: Letrozole 2.5mg PO QD during 16weeks(if needed, maximum for 24 weeks)

Arm Label

Target Number of Participant

Arm Type

Arm Description

Single Arm
1. MammaPrint High Risk group:
Neoadjuvant chemotherapy with AC#4 followed by Docetaxel#4
2. MammaPrint Low Risk group:
	Pre-menopausal patients: Letrozole 2.5mg PO QD+ leuprorelin 3.75mg SQ every 4 weeks during 16weeks(if needed, maximum for 24 weeks)
	Post-menopausal patients: Letrozole 2.5mg PO QD during 16weeks(if needed, maximum for 24 weeks)

Gender

Age

Description

1) Histopathologically and immunohistochemically confirmed ER+ and HER2- BC patients
2) Stage I-IIIA BC patients with detectable tumor sizes
3) BC patients for whom BCS is not feasible due to tumor sizes or locations (two surgeons at each institution evaluate the infeasibility of BCS)
4) Patients without distant metastasis which were identified pathologically or radiologically
5) Female patients ≥ 19 years
6) Patients with formalin-fixed FFPE cancer tissue or 10 unstained cancer tissue slides for Mammaprint test
7) ECOG 0-2
8) Patients with adequate bone marrow function 
    - Hemoglobin 10 g/dL, ANC 1,500/mm3, Plt 100,000/mm3  
9) Patients with adequate kidney function
    - serum Cr ≤ 1.5 mg/dL
10) 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
11) Patients who decided to voluntarily participate in this trial with written informed consent

1) History of treatment for ipsilateral BC or breast carcinoma in situ
2) Confirmed distant metastasis of BC
3) History of cancer other than BC
4) Pregnant (positive pregnancy test within a week of enrollment) or breast-feeding patients 
5) Uncontrolled severe infection
6) Psychiatric illness or epilepsy
7) Inability to understand and willingness to sign a written informed consent
8) Mammographic extensive microcalcification 
9) Multicentral, Bilateral BC
10) History of hypersensitive reaction of medication used for clinical trial.
11) Endometriosis, endometrioma, vaginal bleeding with unknown causes
12) patients who diagnosed with pituitary adenoma
13) Patients who had high risk for bone fracture or osteoporosis

Conversion rate from BCS-ineligible to BCS-eligible patients

After Neoadjuvant systemic treatment and surgery

actual performance rate of BCS

After Neoadjuvant systemic treatment and surgery

Reduction rate of cancer size eligible for BCS

After Neoadjuvant systemic treatment and surgery

pathological complete response

After Neoadjuvant systemic treatment and surgery

clinical response rate

After Neoadjuvant systemic treatment and surgery

Disease Free Survivals

5 years after completion of neoadjuvant systemic treatment and surgery

Ipsilateral breast cancer recurrence

5 years after completion of neoadjuvant systemic treatment and surgery

Response rate of Blueprint subtype

After Neoadjuvant systemic treatment and surgery