Published online Aug 26, 2015. doi: 10.4331/wjbc.v6.i3.231
Peer-review started: April 28, 2015
First decision: May 14, 2015
Revised: May 30, 2015
Accepted: July 21, 2015
Article in press: July 23, 2015
Published online: August 26, 2015
Approximately 80% of breast cancers (BC) are estrogen receptor (ER)-positive and thus endocrine therapy (ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of (1) ovarian function suppression (OFS), usually obtained using gonadotropin-releasing hormone agonists (GnRHa); (2) selective estrogen receptor modulators or down-regulators (SERMs or SERDs); and (3) aromatase inhibitors (AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs (i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs (i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type I are permanent steroidal inhibitors of aromatase, while type II are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs (i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors (palbociclib) and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.
Core tip: In women with breast cancer (BC), the two major endocrine therapies (ET) available are directed at blocking estrogen receptors (ERs) on cancer cells (selective estrogen receptor modulators), or against the key enzyme in the biosynthesis of estrogens (aromatase inhibitors). The new knowledge about molecular mechanisms regulating tumor progression, suggested the existence of a strict relationship between ERs, intracellular signaling pathways, and other growth factors receptor, which justify the escape of a portion of patients from the inhibitory effects of ET. To restore endocrine sensitivity of BC cells, molecular-target therapies are giving encouraging results, but further studies are required to confirm their real usefulness.