Endocrine Therapy of Breast Cancer

Abstract

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

Current medical treatment of estrogen receptor-positive breast cancer

“…Selective estrogen receptor down-regulators have different pharmacologic characteristics, biochemical structure, and molecular activity with respect of SERM, causing down-regulation and degradation of ERs, and inhibiting proliferation of estrogendependent BC cells [35] . SERDs are pure ER antagonist, blocks ERs activity and accelerate their degradation, thus exhibiting exclusively anti-estrogen effects [36] . Fulvestrant, the only SERD approved by FDA to treat patients with BC, has 100-fold the affinity of TAM for ER, in lack of adverse effect on endometrial ERs [37,38] .…”

“…Fulvestrant, the only SERD approved by FDA to treat patients with BC, has 100-fold the affinity of TAM for ER, in lack of adverse effect on endometrial ERs [37,38] . It is useful especially in patients with advancer BC and as second-line therapy in TAM-resistant tumors [36] . Fulvestrant sensitizes ER-negative BC to chemotherapy, showing a synergistic action with various cytotoxic agents, such as docetaxel [39,40] .…”

Use of Proton Pump Inhibitors as Adjunct Treatment for Triple-Negative Breast Cancers. An Introductory Study

“…Targeted endocrine therapies have an important role in treatment of breast cancer, though their use is dependent on the presence of specific markers (1). Such therapy is influenced by the tumor's expression of hormonal receptors for estrogen, progesterone and human epidermal growth factor receptor 2 (HER2).…”

DNA damage and breast cancer

“…In fact, as much as 30% of breast cancers are thought to have some degree of BRCA1 inactivation [9] . Typically, hormone receptor positive cancer-which is not considered refractory to anti-estrogens-will be treated with ER modulators (SERMs) such as Tamoxifen, Raloxifene or selective ER down-regulators (SERDs) like Fulvestrant in an attempt to slow cancer cell growth [13,14] . Radiation therapy is often utilized to instigate DNA damage in these cancers and thus a combination of surgery, radiation (causing DNA damage) and hormonal therapies can be quite successful.…”