Aromatase inhibitor–associated musculoskeletal pain: An overview of pathophysiology and treatment modalities

Abstract

Since their introduction into clinical use in the 1970s, aromatase inhibitors have been a cornerstone of therapy for estrogen-receptor positive breast cancer in postmenopausal women. Unfortunately, this therapy leads to estrogen depletion in the body, which can lead to unpleasant side effects such as menopausal symptoms like hot flashes, insomnia, slightly increased risk of ischemic heart disease, accelerated bone loss leading to higher osteoporosis risk, and most significantly, arthralgias. The joint pain induced by aromatase inhibitor therapy is frequently cited as the leading cause of premature discontinuation; approximately 50% of patients will report new onset or worsening joint pain 1 year after therapy initiation, approximately 30% of patients discontinue therapy after 1 year, and only 50%–68% of patients remain fully compliant with therapy after 3 years. This article will describe risk factors for aromatase inhibitor–associated musculoskeletal syndrome, including genetic predispositions correlated with an increased risk of this syndrome, explain the currently understood pathophysiology, and give an overview of effective treatment options in managing this syndrome.

Altered somatosensory functioning and mechanism‐based classification in breast cancer patients with persistent pain

“…Ais are associated with AIMS which are often described as symmetrical pain and soreness in the joints (arthralgia), musculoskeletal pain or myalgia and joint stiffness, predominantly involving the hands, wrists, and ankles (Hyder et al, 2021). Around half of BCS on Ais experience AIMS, significantly impacting their quality of life (Grigorian & Baumrucker, 2022). In addition, AIMS decreases adherence rates to AI therapy in approximately half of BCS, in turn compromising survival rate (Roberts et al, 2020;Singer et al, 2012).…”

“…Although the specific pathophysiology of AIMS remains unclear, current theories point to estrogen deprivation as a crucial element contributing to bone and cartilage degeneration and the development of musculoskeletal symptoms (Grigorian & Baumrucker, 2022; Tenti et al, 2020). Estrogen reduces osteoclast maturation and lifespan, and increases osteoblast maturation and lifespan.…”

“…In addition, estrogen seems to influence somatosensory processing due to pronociceptive and antinociceptive properties involved in transmission and modulation of noxious stimuli (Coulombe et al, 2011; Tenti et al, 2020). It also has an anti‐inflammatory function decreasing the synthesis of inflammatory cytokines (tumor necrosis factor‐alpha [TNF‐α] and interleukin 1ß), but also increasing C reactive protein (CRP; Grigorian & Baumrucker, 2022). In addition, TNF‐α increases C fiber activity causing an increase in the wind‐up phenomenon at the dorsal horn and hyperalgesia to cold and pressure in rats (Liu et al, 2007; Sorkin et al, 1997).…”

Effects of esters’ cetylated fatty acids taping for chronic neck pain with mobility deficit in patients with breast cancer

“…As reported by WHO ( World Health Organization ), during 2020, about 7.8 million women have survived breast cancer diagnosed in the last 5 years, thus representing the form of cancer with the highest prevalence worldwide [ 1 ]. Surgery, chemotherapy, radiotherapy, and hormonal therapy for breast cancer lead to many consequences, such as inflammation and tissue adherence, causing pain and altering the patients’ quality of life (QoL) [ 3 , 4 ]. The more frequent rehabilitation problems in women with breast cancer are as follows [ 5 – 9 ]: Reduction in upper limb strength and mobility Upper limb lymphedema Chronic pain (benign, regarding joints, and muscles) Fatigue Osteopenia and osteoporosis …”

“…-Reduction in upper limb strength and mobility -Upper limb lymphedema -Chronic pain (benign, regarding joints, and muscles) -Fatigue -Osteopenia and osteoporosis Chronic musculoskeletal pain (CMP) is reported in 60% of breast cancer survivors: shoulder, neck, arm, and thorax are the most common sites of chronic pain, negatively affecting the quality of life [10][11][12]. The origin of musculoskeletal pain in these patients is certainly multifactorial, as a consequence of postural post-surgery disorders, chemo and radiotherapy treatments that can worsen adhesions and consequently postural disorders, but also hormonal therapies that are associated with diffuse musculoskeletal pains (aromatase inhibitor-associated musculoskeletal syndrome (AIMSS)), and finally the psychological impact which constitutes a predisposing factor for the chronicity of pain [3,4,[10][11][12]. A multidisciplinary approach is proposed, including stretching, aerobic exercises, strength exercises, acupuncture, and manual therapy, not only to reduce pain and prevent chronicity, but also to improve QoL [11,13,14].…”