Is breast cancer in women with L-thyroxine supplemented hypothyroidism a less aggressive disease? Retrospective evaluation of risk reduction and clinico-pathological differences

Abstract

22048 Background: A putative association between thyroid function and breast cancer [BC] risk is controversial but retrospective studies suggest a protective effect of hypothyroidism [HYP] in BC. Growing pre-clinical evidence indicates that in cancer thyroid hormone (TH) is mitogenic, anti-apoptotic and pro-angiogenic acting via genomic and non-genomic mechanisms e.g. aνβ-3 integrin. The potential impact of TH on prognosis in cancer therefore requires elucidation since L-thyroxine (L-thy) supplementation in hypothyroid cancer patients might constitute a prognostic variable. Methods: 2,044 electronic and paper charts were reviewed in a hospital based retrospective case-control study on 159 female patients with AJCC stage 1–4 invasive BC patients (infiltrating ductal (129), lobular (19) carcinoma- the majority) over 10 year. 68 cases of invasive BC with primary HYP (on L-thy supplementation) were compared to 91 matched controls -i.e. age, baseline socio-demographics, history of (h/o) estrogen replacement, family h/o BC, pregnancy, body mass index, and menarche. Differences in age of diagnosis, survival and clinic-pathological variables were analyzed. TH blood levels and L-thy dosage were generally unavailable. Chi-square, fisher's exact test and the Wilcoxon 2 sample tests were applied for analysis on SAS 9.0 statistical software program. Results: Compared to euthyroid patients those with HYP were diagnosed with breast cancer 4.7 years later (mean age at diagnosis 68.12 vs. 63.44 years, p <0.035).The tumor measured less than 1 cm in 27.4% of HYP vs. 11.4% of euthyroid patients, p <0.047. HYP patients were also less likely to have lymph node involvement (21.6 vs. 40.5, p <0.28) and more likely to have low S phase fraction (79.4 vs. 60.4, p <0.21). There was insufficient data for thyroid function correlation and survival analysis. Conclusions: This study suggests that in women with L-thyroxine supplemented HYP, breast cancer is diagnosed over 4 ‘asymptomatic’ years later than in a euthyroid cohort and is a less aggressive disease. Prospective studies are required to confirm these findings but in the interim we suggest caution in the TH supplementation of hypothyroid BC patients per ATA consensus guidelines. No significant financial relationships to disclose.