New agents in the first line treatment of metastatic or locally advanced endocrine positive, her-2eu negative breast cancer in postmenopausal women. A review

摘要

Metastatic breast cancer (BC) has a poor prognosis, its treatment having a palliative intention. Owing to the development of new target agents, significant improvements in survival of metastatic BC appear. Similarly to non-metastatic BC, the management of metastatic BC depends on the expression of the hor- mone receptor (estrogen and/or progesterone) and the human epidermal growth factor 2 (Her-2eu). As we know that estrogen hormones stimulate the develop- ment and progression of hormone-receptor positive BC, anti-estrogen therapies remain the most effective endocrine therapy, also in the metastatic setting, by reducing the estrogen production, antagonizing the receptor of estrogen or blocking the signal pathways through the estrogen receptor. However, in a subset of metastatic BCs in postmenopausal women and name- ly hormone positive, Her-2eu negative BCs, a newly developed or acquired resistance to the endocrine ther- apy, reflected by a progression of the disease more than 12 months from the end of the adjuvant endocrine therapy, results in a reduction of the survival outcome?respectively in a lower progression-free survival (PFS) rate. Moreover, the single use of the anti-hormonal agents, letrozol or anastrozole, in the first-line therapy, did not had a significant positive impact on the overall survival rate. On the basis of the low efficiency of hor- monal agents, a new agent has been promoted in the initial anti-hormonal therapy of postmenopausal ER+/ Her-2eu negative metastatic BC. It is the cyclin-de- pendent kinase 4/6 (CDK4/6) inhibitor Palbociclib which, in combination with the aromatase-inhibitor Letrozole, resulted in a significant improvement of the PFS rate. In this paper we address the recent develop- ments on the treatment of locally advanced or meta- static ER+, Her-2eu negative metastatic BC, focusing on the combination of Palbociclib with Letrozole or Fulvestrant, in postmenopausal women.