Dr. Ron’s Research Review – May 11, 2016

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This week’s research review focuses on breast cancer and thyroid disease.

A study examined 102 consecutive BC patients and 100 age-matched control healthy women. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005). In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. (Giani et al., 1996)

T3

The Malmo Preventive Project included 2185 women in whom 149 women were diagnosed with invasive breast cancer. Overall there was a statistically significant association between T3 and "all" breast cancers. The adjusted Hazard Ratio (HR) in the third tertile, as compared to the first, was (1.61:1.07-2.43). There was a statistically significant positive association between the third T3 tertile and large tumors, i.e. > 20 mm, (3.17:1.20-8.36) and the occurrence of lymph node metastases, (4.53:1.60-12.83). (Tosovic et al., 2014)

Thyroid Antibodies

28 studies were included in the meta-analysis. There was significant evidence of an increased risk of BC in patients with autoimmune thyroiditis, evident in a pooled OR 2.92 (95% CI 2.13-4.01). In addition, the results supported an increased risk associated with the presence of anti-thyroid antibodies (OR 2.02, 95% CI 1.63-2.50) and goitre (OR 2.26, 95% CI 1.39-3.69). Subgroup analysis of antibody presence revealed increased risk associated with both anti-TPO (OR 2.64, 95% CI 1.82-3.83) and anti-TG (2.71, 95% CI 1.58-4.69). (Hardefeldt et al., 2012)

TSH Receptor Antibodies

Clinical and laboratory details of 2003 women hospitalized for endocrine disorders were retrospectively analyzed. The coexistence of Graves' disease and breast cancer was statistically significant. We observed thyrotropin (TSH) receptor antibodies (TSHRAb) and TgAb more frequently in patients with breast cancer. We found that TSHRAb is the only variable possessing predictive value for breast cancer. A strong relationship between Graves' disease and breast cancer is proposed. We suggest that TSHRAb could be described as a positive determinant of breast cancer. (Szychta et al., 2013)

Dr. Ron


 

Articles

Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy
            (Giani et al., 1996) Download
The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found among ER, PR status, and the presence of serum thyroid antibodies. In conclusion, 1) the present study provides evidence that the overall prevalence of thyroid disorders is increased in patients with breast cancer, and 2) thyroid autoimmune disorders, especially Hashimoto's thyroiditis, account to a large extent for the increased prevalence of thyroid disease in patients with breast cancer. This feature is independent from the ER and PR status of the primary tumor. The present findings call attention to the usefulness of screening for thyroid disease in any patient with breast cancer.


 

Benign thyroid disease is associated with breast cancer: a meta-analysis
            (Hardefeldt et al., 2012) Download
The controversial relationship between benign thyroid diseases and breast cancer (BC) has been investigated for over 50 years. Despite extensive population studies, the results as a whole have been inconsistent. The purpose of this study was to collate and analyse available data, calculating a pooled odds ratio (OR) of the risk of BC in patients diagnosed with benign thyroid diseases. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Inclusion criteria required a confirmed diagnosis of a benign thyroid disease, reporting of an OR or data to calculate an OR (and 95% confidence interval, CI) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled OR calculated. 28 studies were included in the meta-analysis. There was significant evidence of an increased risk of BC in patients with autoimmune thyroiditis, evident in a pooled OR 2.92 (95% CI 2.13-4.01). In addition, the results supported an increased risk associated with the presence of anti-thyroid antibodies (OR 2.02, 95% CI 1.63-2.50) and goitre (OR 2.26, 95% CI 1.39-3.69). Subgroup analysis of antibody presence revealed increased risk associated with both anti-TPO (OR 2.64, 95% CI 1.82-3.83) and anti-TG (2.71, 95% CI 1.58-4.69). Quantitative analysis of hypothyroidism and hyperthyroidism was not significant. While these results indicate an association between thyroid auto-immunity and BC, further prospective studies are required to definitively prove causality.

TSH receptor antibodies have predictive value for breast cancer - retrospective analysis.
            (Szychta et al., 2013) Download
BACKGROUND: Associations between breast cancer and thyroid disorders are reported in numerous studies. Relationships between thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and breast cancer have been previously demonstrated. However, no analysis has been performed concerning an association between thyrotropin (TSH) receptor antibodies (TSHRAb) and breast cancer. The aim of the study was to evaluate the prevalence of breast cancer or benign breast tumors in patients with Graves' disease and to analyze a possible relationship between Graves' disease and these two groups of breast diseases with emphasis to epidemiology and laboratory findings. PATIENTS AND METHODS: Clinical and laboratory details of 2003 women hospitalized for endocrine disorders were retrospectively analyzed, using an unpaired Student's t-test, logistic regression analysis, chi2 test of independence or the two-sided ratio comparison test. RESULTS: The coexistence of Graves' disease and breast cancer was statistically significant. We observed TSHRAb and TgAb more frequently in patients with breast cancer. We found that TSHRAb is the only variable possessing predictive value for breast cancer. CONCLUSIONS: The strong relationship between Graves' disease and breast cancer is proposed. We suggest that TSHRAb could be described as a positive determinant of breast cancer. The present data call attention to the usefulness of screening for breast cancer in long-term follow-up of patients with autoimmune thyroid disorders, especially of those with Graves' disease. Similarly, screening for autoimmune thyroid disorders should be performed in patients with nodular breast disease. Additionally, the article draws ideas for further research in order to develop targeted treatment for more successful outcome in patients with breast cancer.

T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study.
            (Tosovic et al., 2014) Download
BACKGROUND: The issue of a potential association between thyroid conditions/hormones and breast cancer has been studied extensively during the last decades but the results have been inconclusive and almost no studies have investigated breast cancer aggressiveness. We have previously found a positive association between prospectively measured levels of triiodothyronine (T3) and breast cancer incidence as well as breast cancer mortality. We now investigated prediagnostic T3 levels in relation to specific prognostic factors in breast cancer. METHODS: The Malmo Preventive Project is a population-based prospective cohort including 2185 women in whom T3 levels were measured at baseline. That is, total T3 levels were measured before a potential diagnosis of breast cancer. Mean follow-up was 23.3 years and 149 women in the study population were diagnosed with invasive breast cancer. Tumours were classified according to selected prognostic factors of breast cancer; i.e. grade, tumour size, lymph node metastasis, and hormonal receptor status. T3 was handled both as tertiles and as a continuous variable. A Cox's proportional hazards analysis yielded hazard ratios with 95% confidence intervals. All analyses were also restricted to postmenopausal women. RESULTS: Overall there was a statistically significant association between T3 and "all" breast cancers. The adjusted Hazard Ratio (HR) in the third tertile, as compared to the first, was (1.61:1.07-2.43). There was a statistically significant positive association between the third T3 tertile and large tumours, i.e. > 20 mm, (3.17:1.20-8.36) and the occurrence of lymph node metastases, (4.53:1.60-12.83). Other prognostic factors positively associated with T3 were negative oestrogen receptor (ER) status, (3.52:1.32-9.41) and negative progesterone receptor (PGR) status, (3.52:1.42-8.75). The analyses of T3 as a continuous variable and analysis restricted to postmenopausal women, confirmed the results but also showed an association with smaller tumours and in postmenopausal women a contemporary association with negative lymph nodes. CONCLUSIONS: This prospective study of serum T3 levels in relation to breast cancer aggressiveness is the first of its kind. We found statistically significant positive associations between higher prediagnostic T3 levels and larger tumours, occurrence of lymph node metastases, and negative ER and PGR status.

References

 

Giani, C., et al. (1996), ‘Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy’, J Clin Endocrinol Metab, 81 (3), 990-94. PubMed: 8772562
Hardefeldt, P. J., G. D. Eslick, and S. Edirimanne (2012), ‘Benign thyroid disease is associated with breast cancer: a meta-analysis’, Breast Cancer Res Treat, 133 (3), 1169-77. PubMed: 22434524
Szychta, P, et al. (2013), ‘TSH receptor antibodies have predictive value for breast cancer - retrospective analysis.’, Thyroid Res, 6 (1), 8. PubMed: 23680448
Tosovic, A, et al. (2014), ‘T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study.’, BMC Cancer, 14 536. PubMed: 25060772