Current medical treatment of estrogen receptor-positive breast cancer

Abstract

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 gonadotropinreleasing 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.

ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer

“…epithelium predisposes women to develop breast cancer (Khan et al 1998). This gene controls the growth of luminal subtypes, accounting for ~70% of all breast cancers (reviewed in Lumachi et al 2015). The requirement for ERα in the development and progression of these cancers is well established, and specific drug targeting of ERα has led to improved survival in breast cancer patients over the last 30 years (reviewed in Lumachi et al 2015).…”

Manganese Superoxide Dismutase Acetylation and Dysregulation, Due to Loss of SIRT3 Activity, Promote a Luminal B-Like Breast Carcinogenic-Permissive Phenotype

“…Hormone receptor-positive breast cancer accounts for up to 80% of all invasive breast cancers (55). The cornerstone targeted systemic therapy for this subtype of breast cancer is antihormone therapy (55).…”

“…The cornerstone targeted systemic therapy for this subtype of breast cancer is antihormone therapy (55). There are several antihormone therapy options, including gonadotropin-releasing hormone (GnRH) agonists that lead to ovarian function suppression, selective estrogen receptor modulators or downregulators (SERMs or SERDs), and aromatase inhibitors (AIs) (55).…”

“…Breast cancer as a heterogeneous disease B reast cancer is the most common and frequent nondermatologic malignancy among women in the United States and it is the second cause of cancer death in women (23,55). The expected number of new breast cancer cases in the United States is *231,800 in 2015, which accounts for 29% of all cancers (55).…”

“…The expected number of new breast cancer cases in the United States is *231,800 in 2015, which accounts for 29% of all cancers (55). Breast cancers are clinically categorized into different subtypes according to their pathological estrogen receptor (ER) and progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status; however, molecular studies can further categorize them, linking biology with prognosis (64).…”