Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Abstract

BackgroundThyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.MethodsThyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only.ResultsIn breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy.ConclusionsTaken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy.

T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study

“…Judging from recent observations in various types of malignant tumour disease, this line of research may also lead to new strategies for treatment of breast cancer [32, 33]. …”

Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study

“…Some epidemiological studies have reported increased risks associated with hypothyroidism (8,9), hyperthyroidism (10,11,12), goiter (13) and thyroid autoimmune diseases (14,15), while others have found no association (9,16,17,18). Only four studies employed a cohort design (9,11,12,15); in case-control studies, reverse causation is a plausible competing explanation since breast cancer or its treatment may affect thyroid hormone levels (19). Moreover, some studies have not distinguished between hypothyroidism and hyperthyroidism, despite their contrasting hormonal profiles (13,16,17).…”

Elevated serum levels of free triiodothyronine in adolescent boys with gynaecomastia compared with controls

“…The presence of thyroid hormone receptor alpha (THRa) has been demonstrated Furthermore, thyroid hormones exert effects on breast cancer cells in vitro (19,20). In accordance, a very recent study has demonstrated the presence of both THRa and THRb in breast cancer cells (21).…”