Thyroid and sex hormones have been implicated in mammary tumorigenesis and development.
Effects of estrogen represent an increase in biological activities and therefore, in conjunction with T3 can act directly on mammary tissue by promoting differentiation . Due to these multiple hormonal interactions as well as the ubiquitous role that thyroid hormones play in the body’s overall metabolism, the role that thyroid hormones may play in establishing and maintaining BC is exactly not known. Studies have established a direct action of thyroid hormones on the development of the normal mammary gland. But whether an alteration in thyroid status affects mammary tumor risk as well as development and growth is not entirely clear and needs to be studied further.
Among the BC patients in the present study sample, a considerable number of BC patients (n = 16) reported a past history of thyroid related diseases and among the remaining BC patients, the incidence of subclinical hypothyroidism was twice as high as among apparently healthy individuals. Studies reveal increased risk of BC in women with hyperthyroidism . Indicating an association between level of thyroid function and BC risk and the present study confirms the same for the first time in Sri Lanka.
Among the BC patients even though serum TSH levels were noticeably lower, serum T3 and T4 levels were significantly elevated indicating a possible impact of these on tumor development or progression. Cell line studies reveal that T3 can promote BC cell proliferation and increase the effect of estrogen on cell proliferation. Thus T3 may play a role in BC development and progression .
Circulating estrogens and androgens are found to be positively associated with the risk for BC in premenopausal women . However, previous findings indicate non-significant difference in serum estrogen and progesterone levels in BC patients and significant low levels of testosterone . The higher bioavailability of testosterone counteract the proliferative effects of estrogen on mammary tissue and thereby exert a protective role to the breast, inhibiting cancer development and/or tumour growth  which might be a considerable stakeholder in the study group. Also majority (75%) of the BC patients in the present study were either obese or overweight  and thus the impact of adiposity related secretions of androgens on BC cannot be undermined . A study reveals a synergistic response between T3 and high carbohydrate meals  whereas the BC patients in the present study were not regularly consuming balanced meals but were on frequent carbohydrate rich meals (unpublished observations). Thus the diet, the sedentary lifestyle and being either overweight or obese might have contributed to the present observations.
Lipid-soluble hormones in the blood are bound to hormone-specific transport proteins, while a smaller portion is bound to serum albumin. Testosterone-estrogen-binding globulin (SHBG) is a sex hormone-binding globulin that binds to testosterone and estradiol in the blood. Other known steroid-binding globulins are transcortin, primarily associated with progesterone and thyroxine-binding globulin (TBG), for transporting T4. Increased estrogen concentrations increase TBG concentrations. The rise in TBG is paralleled by a T4 increase to maintain a physiological concentration of free T4. Besides the effects on TBG concentrations, sex hormones also affect deiodinase activity which might together contribute in BC development .
In vitro studies reveal direct stimulatory effects of T3 on basal production of testosterone and estradiol  and according to the present study T3/testosterone above 7.47 indicated the highest risk. In other words, while elevated T3 contribute in BC cell proliferation, lower testosterone concentrations might have reduced the anti-proliferative and pro-apoptotic effect of testosterone on BC. Thus the present study identifies that T3/ testosterone ratio can predict BC with higher odds when compared with other studied thyroid hormones/ sex hormone ratios in identifying BC risk. The imbalance of thyroid hormones causes the dysfunction of the reproductive system  which might also impact on the concentrations of sex hormones.
Interestingly testosterone sometimes functions via conversion to estradiol  and lower testosterone in females might impact on obesity and poor glucose control. Considering the HbA1c levels 20% of BC patients showed values above 7% after excluding 13% of BC patients who were already on glycemic control drugs at the time of enrolment to the study.
However further studies are needed to confirm the exact impact of lower serum testosterone and elevated T3 on developing BC as research on molecular mechanisms involving androgenic pathways in BC is still in their infancy.