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.

      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. 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.

      Accordingly, 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. Although adjuvant therapy is conducted after the completion
      of this study, in case there is progressive disease (PD) after neoadjuvant endocrine therapy,
      adjuvant chemotherapy is conducted.