Clinical Thyroidology® for the Public

Summaries for the Public from recent articles in Clinical Thyroidology
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HYPOTHYROIDISM
Thyroid hormones enhance the growth of estrogen receptor– positive breast cancers

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BACKGROUND
Some studies have suggested an association between thyroid disorders and breast cancer where thyroid hormone appears to play an important role. This goes both ways, as patients diagnosed with breast cancer have a higher risk than the general population of developing thyroid cancer later in life, while patients with thyroid cancer have a higher risk of also developing breast cancer. Moreover, high thyroid hormone levels into the hyperthyroidism range, either due to hyperthyroidism or to over-replacement of thyroid hormone in hypothyroidism, have been associated with an increased incidence and more aggressive types of breast cancer. Some laboratory studies have suggested that thyroid hormone stimulates breast cancer cell growth. Further, up to 30% of patients with breast cancer are on thyroid hormone for treatment of hypothyroidism. This study aimed at investigating the effects of thyroid hormone treatment for hypothyroidism on the outcome of patients with stage I breast cancer.

THE FULL ARTICLE TITLE
 Wahdan-Alaswad RS et al 2021 Exogenous thyroid hormone is associated with shortened survival and upregulation of high-risk gene expression profiles in steroid receptor-positive breast cancers. Clin Cancer Res 27:585–597. PMID: 33097494.

SUMMARY OF THE STUDY
This study examined the association between thyroid hormone therapy, disease-free survival (DFS), and disease-specific survival (DSS) in two groups of patients with stage I lymph node negative breast cancer. The first group included 820 patients treated for breast cancer between 1962 and 1993 and followed for an average of 10 years. Of this group, 69 patients (8.4%) were taking thyroid hormone for hypothyroidism. The second group included 160 patients treated more recently between 2006 and 2009 and followed for a average of 9 years.

Of this group, 50 patient (31.3%) were taking thyroid hormone for hypothyroidism. Data regarding the patient age, cancer size, presence or absence of estrogen receptors (ER + or -) in the cancer, and cancer treatment regimen were included in the analysis. The authors also performed experiments in the laboratory using human breast cancer cell lines to investigate the mechanisms underlying the effects of thyroid hormone and estrogen on breast cancer cells.

In patients with ER+ breast cancer, thyroid hormone therapy was associated with a significantly increased risk of recurrence and death, independently of age, cancer size and grade, while thyroid hormone therapy in patients with ER– breast cancer was not associated with worse outcomes. At 10 years of follow-up, the cancer recurrence rate was 39.5% and the DFS was 72.5 months in ER+ breast cancer patients on thyroid hormone therapy compared to 16% and 106 months, respectively in those not taking thyroid hormone therapy. The death rate was 24% and the DSS was 84 months in ER+ breast cancer patients on thyroid hormone therapy versus 8% and 114 months, respectively in those not taking thyroid hormone therapy. Patients with ER+ breast cancer taking both tamoxifen therapy for breast cancer and thyroid hormone therapy experienced the shortest DFS survival of all groups studied at 10 years, with an average DFS of 52 months vs. 65 months in patients taking tamoxifen without thyroid hormone therapy.

Laboratory studies revealed that therapy with thyroid hormone or estrogen stimulates cell growth, the effect being stronger with combination therapy (thyroid hormone and estrogen). Thyroid hormone and estrogen appeared to stimulate cell growth significantly at all dose levels, including levels in the normal range for both hormones.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The study shows that stage 1 ER+ breast cancer patients treated with thyroid hormone for management of hypothyroidism have worse outcomes, even in patients taking other cancer drugs. These results suggest that treatment with thyroid hormone in patients with hypothyroidism and breast cancer should be closely monitored to ensure that the thyroid hormone levels remain in the normal range.

— Alina Gavrila, MD, MMSC

ABBREVIATIONS & DEFINITIONS

Hyperthyroidism: a condition where the thyroid gland is overactive and produces too much thyroid hormone. Hyperthyroidism may be treated with antithyroid meds (Methimazole, Propylthiouracil), radioactive iodine or surgery.

Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.

Disease-free survival (DFS): defined as the period after the cancer treatment when the patient survives without any cancer signs or symptoms. Disease-specific survival (DSS): defined as the period that begins at the time of diagnosis or at the start of treatment and ends at the time of death specifically from the cancer.

Hormone receptor: a molecule located on a cell membrane or inside the cell that is activated by binding a specific hormone and induces specific changes in the cell function. Estrogen (ER) and thyroid hormone receptors (THR) are members of the nuclear receptor family that bind estrogen and thyroid hormone, respectively and affect gene expression in the cell.

Tamoxifen: medication that blocks the effects of estrogen on breast tissue. It is used to prevent and treat breast cancer.

Cancer recurrence: this occurs when the cancer comes back after an initial treatment that was successful in destroying all detectable cancer at some point.

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