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 hormone receptor (estrogen and/or progesterone) and the human epidermal growth factor 2 (Her-2/neu). As we know that estrogen hormones stimulate the development 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 namely hormone positive, Her-2/neu 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 hormonal agents, a new agent has been promoted in the initial anti-hormonal therapy of postmenopausal ER+/ Her-2/neu negative metastatic BC. It is the cyclin-dependent 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 developments on the treatment of locally advanced or metastatic ER+, Her-2/neu negative metastatic BC, focusing on the combination of Palbociclib with Letrozole or Fulvestrant, in postmenopausal women.
Keywords: breast cancer, estrogen receptors, overall survival.
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