Endocrinology and hormone therapy in breast cancer: Aromatase inhibitors versus antioestrogens

Methoxylation, however, decreases activity e.g., 7-hydroxyflavanone (56) was more active than 7-methoxyflavanone (58). Prenylation generally caused substantial increases in aromatase activity e.g., 8-prenylnaringenin (62), (2S)-abyssinone II (45), and (2S)-euchrenone a7 (51) except in the case of isoxanthohumol (57). When results were reported as μg/mL, the most active extracts in the microsomal assay included a water reflux extract of Euonymus alatus (Thunb.) Sielbold (“gui-jun woo” in Korean folk medicine), a dichloromethane partition of Isodon excisus Kudo var. Don 111, and a polyphenol-enhanced extract of green tea (Camellia sinensis Kuntze) 112. Interestingly, this study also reported that cigarette smoke (obtained using methylene chloride and aqueous traps) and tobacco leaves (70% ethanol extract; Nicotiana tabacum L.) also potently inhibited aromatase, as reported in cigarette equivalents 113.

Aromatase in highly estrogen-sensitive tissues, such as the breast, uterus, vagina, bone, brain, heart and blood vessels, provides local estrogen in an autocrine fashion (Figure 2). The aromatase gene promoter in breast tissue is less sensitive than the gene promoter in the ovary to fluctuations in LH but much more sensitive to increases in inflammatory cytokines. Circulating inflammatory cytokines increase with age, and breast tissue inflammatory cytokines increase with proliferative breast disease and breast cancer. Thus, it comes as little surprise that breast aromatase activity is increased in proliferative breast disease and many cases of breast cancer (2). Neoadjuvant therapy refers to any treatment including chemotherapy, endocrine therapy, or radiation that is given prior to surgery. This can be a mean to down-stage the tumor to improve the chance for patients to undergo breast-conserving surgery (BCS) 65 and, more attractively, providing an in vivo measurement of tumor response 36, 66.

Damage to vascular walls and DNA may be caused by inducible nitric oxide synthase (iNOS), which occurs in humans with atherosclerosis and tumor genesis. Quercetin and resveratrol at micro-molar ranges were able to suppress iNOS gene expression and reduce nitric oxide production. Further, polyphenols scavenged nitric oxide under physiologic conditions 37. While ethanol did not reduce iNOS or nitric oxide production, when it was present in the range of 0.1% to 0.75%, it enhanced the activity of grape polyphenols in a concentration-dependent manner 37. Laboratory findings before and during treatment with https://www.gt.tours/winstrol-stanozolol-injectable-50-mg-elbrus-44/ aromatase inhibitor in male patients 1 and 3.

• The shift from tamoxifen to an AI in both the advanced and adjuvant setting has challenged the status of tamoxifen as the ‘gold standard’ treatment for postmenopausal women with hormone-receptor-posistive breast cancer.
• Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men,12 and gynecomastia in men.
• Aromatization is the process that converts testosterone into estrogen, which is a natural process that your body goes through to maintain homeostasis, as your body has to have a good testosterone to estrogen ratio.
• Reports of MSAEs linked to CDK4/6 inhibitors from the first quarter (Q1) of 2015 and 2023 Q4 were extracted from the FAERS.
• However, arthralgias, fatigue, dyspareunia, reduced libido and hot flushes may result in poor uptake and/or compliance.

When should I call my healthcare provider?

Additionally low dose (0.1 μM to 10 μM) combinations of the phytoestrogens were also effective in the reduction of aromatase mRNA levels using human ovarian tissue 70 (see Table 1). Hormone-dependent breast cancer and other endocrine disorders prompted investigators to develop potent and selective aromatase inhibitors. One approach was to target the aromatase enzyme using analogs of natural steroidal substrates in order to determine the structure/function relationship of the aromatase conversion process.

What are the side effects?

Though the other sesquiterpene lactone 10-epi-8-deoxycumambrin B (210) was found to be moderately active in microsomes it was found to be cytotoxic in further testing 161. The former was moderately active as an aromatase inhibitor in JEG-3 choriocarcinoma cells and was not cytotoxic 161. Examples of first1, second2, and third3 generation AIs, including AIs currently in clinical trials4.

A number of studies shown that the drugs may be beneficial in premenopausal women whose ovaries have suppressed with gonadotropin-releasing hormone agonists (GnHRa). Aromatase inhibitors should not be used in people with a known hypersensitivity to any of the active or inactive ingredients in the drug. With that being said, a drug allergy is not common with aromatase inhibitors, affecting less than one out of 10,000 users. Aromatase inhibitors work by binding to aromatase and preventing aromatization from occurring. By doing so, the production of estrogen may be reduced by as much as 95% in postmenopausal women.

In contrast, the patient’s PBL exhibited significant aromatase activity and full-length mRNA, driven mostly by exon I.2 containing transcripts originating from the allele with the microdeletion. Interestingly, in these PBL cortisol decreased aromatase activity, which might be attributed to cortisol acting on the DMXL2 promoter. AIs are classified as type 1 steroidal (noncompetitive, irreversible) or type 2 nonsteroidal (competitive, reversible) inhibitors.

Aromatase inhibitors as extended endocrine adjuvant therapy

Copyright © 2024 Giannopoulou, Brandt, Zorn, Denzer, von Schnurbein, Fukami, Kaiser, Schmidt and Wabitsch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Clinical characteristics at presentation of patients 1, 2 and 3 with aromatase excess syndrome. Another relevant aspect is to consider letrozole plasma concentrations achieved during the chronic administration of the drug.