An Underestimated Toxicity Radiation-Induced Hypothyroidism in Patients Multimodally Treated for Breast Cancer

Abstract

Radiation therapy is part of the therapeutic arsenal for breast cancer, whether it is adjuvant treatment after lumpectomy or radical mastectomy, or it is used as a palliative option in the case of metastatic or recurrent disease. Significant advances in diagnostic and therapeutic stratification of breast cancers have significantly prolonged survival, even in the metastatic stage. Exposure of patients during the course of the disease in a multidisciplinary therapeutic approach including chemotherapy, hormone therapy, targeted anti-HER therapies or CDK4/6 inhibitors had led to improved survival but with the price of additional toxicity. Among them, hypothyroidism is a well-known consequence of external radiation therapy, especially in the case of cervical region irradiation, including supraclavicular and infra-clavicular nodal levels. In this situation, the thyroid gland is considered as an organ at risk (OAR) and receives a significant dose of radiation. Subclinical hypothyroidism is a common endocrine disorder characterized by elevated TSH levels with normal levels of FT4 (free T4) and FT3 (free T3), and as a late effect, primary hypothyroidism is one of the late effects that significantly affects the quality of life for patients with breast cancer receiving multimodal treatment. Hypothyroidism has a significant impact on quality of life, most often occurring as late clinical toxicity, secondary to thyroid irradiation at doses between 30 and 70 Gy. Dose-volume parameters of irradiation, gland function at the beginning of the treatment and associated systemic therapies may be factors that alter thyroid radio-sensitivity and affect thyroid gland tolerance. In the case of head and neck tumor pathology, in which doses of >50 Gy are routinely used, the thyroid gland is generally considered as an OAR, the rate of radio-induced hypothyroidism being estimated at rates of between 20% and 52%. For breast cancer, the thyroid is often neglected in terms of dosimetry protection, the rate of late dysfunction being 6–21%.

Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis

“…In total, 34 full text papers were assessed for eligibility. After excluding 14 papers [7,[22][23][24][25][26][27][28][29][30][31][32][33][34], 20 studies were included in the systematic review [8][9][10][16][17][18][19][20][21][35][36][37][38][39][40][41][42][43][44][45]. Of these, 12 were included in one or several of the meta-analyses.…”

Mexican breast cancer consensus. Multidisciplinary care in breast cancer

“…Up to 21% of patients may develop it during the first nine months after RT conclusion when the supraclavicular region is treated. Thyroid function tests should ideally be taken before starting RT and during the first six months after RT completion with semiannual follow-up for the ensuing five years 59 .…”

Consenso mexicano de cáncer mamario. Cuidados multidisciplinarios en cáncer de mama

“…Hasta el 21% de las personas pueden desarrollarlo durante los primeros nueve meses posteriores al término de RT cuando se trata la región supraclavicular. Idealmente deben tomarse pruebas de función tiroidea antes de iniciar la RT y durante los primeros seis meses posteriores al término de esta con seguimiento semestral durante los siguientes cinco años 59 .…”