Thyroid hormones and breast cancer-prospective studies on incidence, mortality and prognostic factors

Thyroid hormones and breast cancer-prospective studies on incidence, mortality and prognostic factors The aim of this thesis was to investigate in a prospective design, thyroid hormones in relation to breast cancer risk, mortality and prognostic factors. The association between total triiodothyronine (T3) levels and breast cancer risk was studied in 2185 women with146 incident breast cancer cases. The association of free T3 and free thyroxin (T4) levels in relation to breast cancer risk was studied in 676 breastcancer cases and 680 controls. It was found that: Total T3 levels in postmenopausal women are positively associated with the risk of developing breast cancer in a dose-response manner. Free T4 levels also appear to be positively associated with a higher risk of breast cancer. The association between thyrotropin (TSH) levels and breast cancer risk was studied in 2696 women with173 incident breast cancer cases. The association between TSH and thyroid peroxidase antibodies (TPO-Ab) and breast cancer risk was studied in 676 breastcancer cases and 680 controls. It was found that: Women with a high level of TPO-Ab have a slightly lower risk of breast cancer, whereas TSH levels are not associated with breast cancer risk. The association between total T3 and prognostic factors in breast cancer and breast cancer mortality was studied in 2185 women where 26 died from breast cancer. It was found that: Total T3 levels are positively associated with breast cancer-specific mortality, which is not related to a general effect on all-cause mortality. Total T3 levels have a positive association to negative prognostic factors in breast cancer such as the occurrence of lymph node metastases, and negative oestrogen and progesterone receptor status. It is concluded that thyroid hormone levels are positively related to breast cancer risk and prognosis

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

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

Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women

Introduction: The potential association between hypo-and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women. Methods: In the Malmo Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Cox's proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre-and peri/postmenopausal women separately. Results: Overall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer. Conclusions: This is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

Background: Results from several cohort and case–control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1–4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1–1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60–0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas

Triiodothyronine (T3) levels in relation to mortality from breast cancer and all-causes: a population-based prospective cohort study.

OBJECTIVE: The potential association between thyroid hormones and breast cancer has been investigated in a large number of studies without conclusive results. This study investigated T3 levels in relation to breast cancer mortality in a population with no breast cancer patients at baseline. An additional aim was to study T3 levels in relation to mortality from other cancers and all-cause mortality. DESIGN AND METHODS: This was a population-based prospective cohort study including 2,185 women in whom T3 levels were measured as part of a preventive health project, i.e. before diagnosis in women who later developed breast cancer. Mean follow-up was 24.1 years and record-linkage to The Swedish Cause-of-Death registry identified 471 women who died; 26 out of breast cancer, and 182 from other cancers. Mortality was assessed using a Cox's analysis, yielding hazard ratios (HR), with 95% confidence intervals. Analyses of T3 as a continuous variable were repeated for pre- and peri/postmenopausal women separately. RESULTS: T3 levels were positively associated with the risk of breast cancer specific death in the age-adjusted analysis: HR for T3 as a continuous variable was 2.80 (1.26-6.25). However, the crude analysis did not reach statistical significance. Breast cancer mortality was even higher in postmenopausal women: 3.73 (1.69-8.22), but stratified analyses included few events. There were no statistically significant associations between T3 levels and deaths from other cancers, age-adjusted HR: 1.09 (0.72-1.65) or all-cause mortality (1.25:0.97-1.60). CONCLUSIONS: This study, the first of its kind on prospectively measured T3 levels, indicates that T3 levels are positively associated with breast cancer specific mortality, and that this is not related to a general effect on all-cause mortality

prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk.

Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones / auto antibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause-effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of the present study was to investigate pre-diagnostically measured levels of thyroid hormones, thyrotropin, and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free T3, free T4, TSH, and TPO-Ab levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10-1.77). This association was most pronounced in overweight women (1.51:1.07-2.12). Women with high levels of TPO-Ab had a lower risk of breast cancer, but only the analysis of TPO-Ab as a continuous variable reached statistical significance. Free T4 was in this study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO-Ab had a relatively low risk of breast cancer. © 2012 Wiley-Liss, Inc

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

Background: Results from several cohort and case–control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1–4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1–1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60–0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

Background: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR = 0.77; 95% CI = 0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas