Breast Cancer: Targeting of Steroid Hormones in Cancerogenesis and Diagnostics

Abstract

Breast cancer is the most common malignancy in women with high mortality. Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are needed for the diagnosis, treatment and prognosis of breast cancer and many other diseases. At present, non-invasive diagnostic methods are gaining more and more prominence, which enable a relatively fast and painless way of detecting many diseases. Metabolomics is a promising analytical method, the principle of which is the study and analysis of metabolites in biological material. It represents a comprehensive non-invasive diagnosis, which has a high potential for use in the diagnosis and prognosis of cancers, including breast cancer. This short review focuses on the targeted metabolomics of steroid hormones, which play an important role in the development and classification of breast cancer. The most commonly used diagnostic tool is the chromatographic method with mass spectrometry detection, which can simultaneously determine several steroid hormones and metabolites in one sample. This analytical procedure has a high potential in effective diagnosis of steroidogenesis disorders. Due to the association between steroidogenesis and breast cancer progression, steroid profiling is an important tool, as well as in monitoring disease progression, improving prognosis, and minimizing recurrence.

Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial

“…Nevertheless, in the long-term use, the preventive effects of aspirin on BC may be attributed to the other pathways [ 24 , 26 , 35 ], and they are probably more important than their effects on estrogen levels. Second, given that estrogen levels were significantly higher in BC tissue than in plasma and that local estrogen production plays an essential role in the proliferation of invasive breast cancer cells in postmenopausal women [ 19 ], in the long term, locally chemopreventive effects of aspirin on breast tissue [ 30 ] may be more important than those on circulating levels [ 11 ]. Third, the importance of measuring estrogen metabolites in BC has received less attention.…”

“…In line with this, a dose-response meta-analysis [ 16 ] of cohort studies from approximately 1 million people concluded that the optimal aspirin dose for the chemoprevention of BC might be in the range of < 325 mg per day, 2–7 times/week, accompanied by long-term administration (> 5 years). Given the chemopreventive effects of aspirin in BC [ 17 , 18 ] and the relations between high serum levels of steroids (estrogens and androgens) and increased BC risk in postmenopausal women [ 19 – 21 ], some studies were deliberated on introducing aspirin dosing to lower estrogen levels. However, these studies [ 17 , 22 , 23 ] and a randomized clinical trial (RCT) [ 11 ] did not succeed in concluding that the dose, frequency, and duration of aspirin use observed in the prevention of BC necessarily complied with those of estrogen lowering.…”

Black Elder and Its Constituents: Molecular Mechanisms of Action Associated with Female Reproduction

“…Therefore, the available publications indicate both stimulatory and inhibitory actions of elderberry extract and its constituents rutin, anthocyanins and lectins on regulators of embryogenesis, embryonal cancerogenesis and steroidogenesis. The ability of steroid hormones to promote both embryo development [108] and malignant transformation [109] is well-known. Therefore, the influence of elderberry molecules' action on embryo and cancerogenesis through the estrogen/estrogen receptor system could be proposed.…”

“…These observations suggest that steroid hormones could be one of the mediators of the black elderberry and its molecule rutin on ovarian functions, and so can promote ovarian cell viability through the stimulation of steroidogenesis [98]. Finally, the influence of elderberry extract on embryonal cancer cell estrogen/estrogen receptor systems [57], as well as the importance of this system in control of embryogenesis [108] and cancerogenesis [109], indicate that elderberry can affect embryos via estrogens and its receptors. Nevertheless, such hypotheses require direct experimental confirmation.…”

Tumor-Associated Macrophages: Critical Players in Drug Resistance of Breast Cancer

“…The morbidity and mortality of different molecular subtypes of BC differ (6). Distinct subtypes of BC are usually treated with different ways in clinical management (7). Drug therapy can be roughly divided into endocrine therapy, chemotherapy, targeted therapy, and immunotherapy (8).…”