The Potential Role of Nutraceuticals as an Adjuvant in Breast Cancer Patients to Prevent Hair Loss Induced by Endocrine Therapy

Abstract

Nutraceuticals, natural dietary and botanical supplements offering health benefits, provide a basis for complementary and alternative medicine (CAM). Use of CAM by healthy individuals and patients with medical conditions is rapidly increasing. For the majority of breast cancer patients, treatment plans involve 5-10 yrs of endocrine therapy, but hair loss/thinning is a common side effect. Many women consider this significant, severely impacting on quality of life, even leading to non-compliance of therapy. Therefore, nutraceuticals that stimulate/maintain hair growth can be proposed. Although nutraceuticals are often available without prescription and taken at the discretion of patients, physicians can be reluctant to recommend them, even as adjuvants, since potential interactions with endocrine therapy have not been fully elucidated. It is, therefore, important to understand the modus operandi of ingredients to be confident that their use will not interfere/interact with therapy. The aim is to improve clinical/healthcare outcomes by combining specific nutraceuticals with conventional care whilst avoiding detrimental interactions. This review presents the current understanding of nutraceuticals beneficial to hair wellness and outcomes concerning efficacy/safety in breast cancer patients. We will focus on describing endocrine therapy and the role of estrogens in cancer and hair growth before evaluating the effects of natural ingredients on breast cancer and hair growth.

Keywords: aromatase inhibitors; breast cancer; endocrine therapy-induced hair loss; estrogen receptor; hair follicle; nutraceuticals; plant extract; tamoxifen.

Figure 3

The human hair cycle. Hair follicles cycle throughout life with a growing phase (anagen) followed by regression (catagen) and maintenance (telogen). The hair fiber is shed during exogen, which usually coincides with the start of a new cycle. Bulb matrix cells proliferate and differentiate to produce the new follicle and hair fiber. In their center, the dermal papilla directs the type of hair produced. During catagen, the lower hair follicle regresses before entering telogen, where the hair fiber is firmly anchored but no further growth occurs. The length of anagen and telogen vary and will determine overall hair growth. If hair is shed before the initiation of a new anagen, the hair follicle may sit empty, a stage known as kenogen. Shortened anagen, lengthened telogen and increased exogen/kenogen can result in hair thinning. The number of hair follicles in kenogen is increased in women with female pattern hair loss (FPHL) [50].

Figure 1

Regulation of estrogen-response genes by 17β-estradiol and tamoxifen. Estradiol (E2) (pink circles) passes through the cell membrane and binds to the estrogen receptor (ER), inducing a conformational change in shape and nuclear translocation, where it interacts with specific estrogen response elements (ERE) that regulate estrogen responsive genes, after recruiting cell-specific cofactors (CoA). E2 can be metabolized by aromatase from androgen precursors (blue circles; dehydroepiandrosterone (DHEA) or testosterone (T)). In breast cells, binding of tamoxifen (Tam) to ERs results in a conformational change that recruits corepressors (CoR) of gene transcription. However, in the endometrium, tamoxifen binding to the ER results in protein:protein interactions and activation of the activator protein 1 (AP-1) promotor.

Figure 2

The biosynthesis of estrogen from inactive circulating precursors in breast cancer. Bioactive estrogen can be synthesized by breast cancer cells and breast stromal tissue from circulating precursor steroids. These include the adrenal androgens dehydroepiandrosterone (DHEA) and androstenedione (A-dione); dehydroepiandrosterone sulphate (DHEA-S), the major circulating androgen, and estrone sulphate (E1-S), the major circulating estrogen in postmenopausal women, which can be converted to DHEA and estrone (E1), respectively, by steroid sulfatase (STS). DHEA and androstenediol are metabolized by 3β- hydroxysteroid dehydrogenase (3β-HSD) type 1 to the estrogen precursors A-dione and testosterone. Testosterone can be metabolized by 5α-reductase to the potent androgen 5α-dihydrotestosterone (5α-DHT), which has a high affinity for the androgen receptor (AR). Type 1 3β-HSD can convert 5α-DHT to 5α-androstane-3β,17β-diol (5β-diol), which is an agonist of both the AR and the estrogen receptor (ER). Aromatase is required for the conversion of testosterone to 17β-estradiol and conversion of A-dione to E1, which can be further metabolized by 17β- hydroxysteroid dehydrogenase (17β-HSD) type 1 to 17β-estradiol, which has a high affinity for ER.

Figure 4

17β-estradiol as an antioxidant. The antioxidant cycle for 17β-estradiol by transfer of a H-atom to a free radical (^•OH), to form a phenoxyl radical that scavenges ^•OH forming a para-quinol which undergoes enzymatic reduction in the presence of the cofactor nicotinamide adenine dinucleotide phosphate (NADPH) to convert back to 17β–estradiol.