Materia Medica Perspective
Management of Endocrine Therapy Adverse Effects in Breast Cancer Survivors: A New Guideline SAM ARONSON, PHARMD CANDIDATE AND KAREN M. FANCHER, PHARMD, BCOP ormone-receptor positive breast cancer makes up between 70 and 80 percent of all breast cancer cases.1 The long-term management of breast cancers, specifically hormone-receptor positive breast cancer, has improved dramatically in recent history. The use of estrogen-regulating therapy has contributed to some of these impressive improvements. There are five agents that are recommended for the prevention of recurrence in hormone receptor-positive breast cancer. The first agent is tamoxifen (Nolvadex®, Sotamox®), which is a selective estrogen receptor modulator and is the most well-established adjuvant endocrine therapy. It is the preferred agent in pre-menopausal women as it has some estrogen-like effects and will not induce menopause. 2 Three of the other agents are aromatase inhibitors, and include anastrozole, letrozole, and exemestane. All these agents will block the synthesis of estrogen entirely. Anastrozole (Arimidex®) and letrozole (Femara®) are non-steroidal aromatase inhibitors and are preferred on most insurance formularies. Exemestane (Aromasin®) is a steroidal aromatase inhibitor and is generally reserved for patients non-responsive to both tamoxifen and the non-steroidal aromatase inhibitors.2,3 The final agent is fulvestrant
H
(Faslodex®), which is an estrogen receptor antagonist that also leads to the downregulation of estrogen receptors.2 It is the most aggressive of the adjuvant endocrine therapies and has the most adverse effects. Each of these agents is recommended to be used for 5-10 years after the completion of surgery, chemotherapy and/or radiation to prevent recurrence of hormone-receptor positive breast cancer.3 On April 20, 2021, Lancet Oncology published a new guideline titled “Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer” regarding the management of adverse effects caused by these hormonal therapies.4 All these agents share a similar adverse effect profile, and patients may be dealing with those adverse effects for 5-10 years. This article will serve to review and summarize the adverse effects caused by adjuvant endocrine therapy and how to manage them based on the guidelines.
Hot flashes The first major adverse effect that these patients face are hot flashes. Both pharmacological and non-pharmacological management of this adverse effect has been studied. The most well-studied agent is
venlafaxine (Effexor®). Based on several randomized controlled trials which studied women who have breast cancer and were experiencing hot flashes, venlafaxine has been shown to reduce hot flashes by up to 60%.4-6 Doses ranging from 37.5 to 150 mg daily have been studied, and while the higher doses tend to be more effective, they are also associated with higher incidence rates of xerostomia, decreased appetite, nausea, and constipation.4,7 Other selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) have also been studied and have shown positive results, but none as extensively as venlafaxine. Fluoxetine (Prozac®) and paroxetine (Paxil®) are SSRIs that are strong CYP2D6 inhibitors, and sertraline (Zoloft®) is a moderate CYP2D6 inhibitor, and all three of these agents could potentially decrease the bioavailability, and subsequently the efficacy of tamoxifen, which should be considered in our patients.4,8,9 Gabapentin and pregabalin (Neurontin® and Lyrica®, respectively) also have some data behind them for treating hot flashes and have similar efficacy rates to venlafaxine. In trials that compared these agents to venlafaxine, patients preferred venlafaxine due to the more tolerable adverse effect profile.4,10 Clonidine (Catapres®) was also studied Continued on page 300
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