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Breast Cancer and Early Contact with Bovine Milk

10. Breast Cancer and Thyroid Disease

Stand / Letzte Aktualisierung durch Elisabeth Rieping 2004/07/27

The link between breast cancer and thyroid disease has induced many studies out of which the following picture emerges:

Prospective follow-ups of patients with thyroid disease show that they seem to be no more prone to develop mammary carcinoma
than the average person [i],[ii],[iii],[iv].

On the other hand, breast cancer patients have a high incidence of goitre [v],[vi],[vii] a condition reflecting the compensation of
iodine deficiency, which does not have to be associated with abnormal hormone concentration. In regions with high iodine supply,
for example in the Germany of today, where the foood is enriched with iodine, and where is enough iodine for the thyroid and for
the cells of breast cancer and its metastases, no goitre will develop. But in Turkey the development of goitre is still found
today[viii].

The reason for the iodine uptake can be seen in the task of the breast to supply the child with iodine[ix] during lactation. The
lactating breast shows a 20 to 30 fold accumulation of iodine compared to blood [x],[xi].

In breast cancer cells this function seems to be active independent of lactation. For mouse mammary tumor cells it was shown that
the iodine uptake could be further stimulated by estrogens, differing from the uptake by thyroid cells depending on thyroid
stimulating hormone TSH[xii]. This difference in regulation is now looked for to enable therapy of human breast cancer without
removing the thyroid[xiii] ,[xiv].

There is also histological evidence for a nodular formation in thyroid organs accompanied by hyperthrophy of pituary TSH
producing cells[xv], probably developing in response to the activity of iodine trapping tumor cells.
Because of the excellent results of treatment of the differentiated thyroid carcinoma with radioactive iodine[xvi], a similar treatment
of breast carcinoma should be worth testing.

Especially in patients showing development of goitre, as this condition hints not only to the survival of active tumor cells, what is
reflected in the shorter survival time of these patients[xvii], but also to an accumulation of iodine by the metastatic cells, this should
be promising. The appearance of antibodies against thyreoglobulin or transperoxidase which occur during lactation and breast
cancer can be seen as a sign of an active iodine accumulation by the breast too.

The enzymes which do the uptake of iodine, the sodium/iodide symporter called NIS, have been isolated and shown to be active in
the healthy lactating gland and in mammary tumors. More than 80% of isolated of human breast cancer samples expressed the
symporter compared to none of the normal nonlactating samples from reductive mammoplasties[xviii].

Since it is known for longer time that breast tissue may take up iodine, the risk of breast cancer was feared for women being treated
with radioactive iodine 131 for hyperthyroidism. But the results of a risk evaluation showed that the risk was not elevated but
reduced after the treatment.

The relative risk for breast cancer in patients with hyperthyroidism treated with radioactive iodine was 0.7 compared to those
treated surgically [xix]. That could mean that small developing breast cancers had been killed as a side effect of the iodine 131
therapy aimed at treating the hyperthyroidism.

[i] Wynder EL, Bross IJ, Hirayama T. A study of the epidemiology of cancer of the breast. Cancer. 1960 May-Jun;13:559-601.

[ii] Levy J, Levy JA, Role of the hypometabolic state in breast cancer. Am Pract Digest Treat 1951; 522-526.

[iii] Schottenfield D, The relationship of breast cancer to thyroid disease. J Chron Dis 1968; 21: 303-313.
[iv] Hedley AJ, Jones SJ, Spiegelhalter DJ, Clements P, Bewsher PD, Simpson JG, Weir RD. Breast cancer in thyroid disease: fact
or fallacy? Lancet. 1981 Jan 17;1(8212):131-3.

[v] Dassaive P, Observations cliniques en faveur de L’existence de ralations entre la fonction thyroidienne et le compartment de
cancer heterologues. Acta Chir Belge1956 ; 55 :25-49.

[vi] Humphrey LJ, Swerdlow M, The relationship of breast disease to thyroid disease. Cancer 1964; 17: 1170-1176.

[vii] Backwinkel K, Jackson AS. Some features of breast cancer and thyroid deficiency. Cancer 1964; 17: 1174-1176.

[viii] Turken O, NarIn Y, DemIrbas S, Onde ME, Sayan O, KandemIr EG, YaylacI M, Ozturk A. Breast cancer in association with
thyroid disorders. Breast Cancer Res. 2003;5(5):R110-3

[ix] Eskin BA, Parker J, Bassett JG, George DL. Human breast uptake of radioactive iodine. Obstet Gynaecol 1974, 44: 398-402.

[x] Brown-Grant K. The iodide concentrationg mechanismof the mammary gland. J Physiol (lond) 1975;

135: 644-654.

[xi] Brown-Grant K. Extrathyroidal iodide concentration mechanisms. Physiol Rev 1961; 41:189-213.

[xii] Thorpe SM. Increased uptake of iodide by hormone-responsive compared to hormone-independent mammary tumours in GR
mice. Int J Cancer 1976; 18:345-350.

[xiii]Upadhyay G, Singh R, Agarwal G, Mishra SK, Pal L, Pradhan PK, Das BK, Godbole MM. Functional expression of sodium
iodide symporter (NIS) in human breast cancer tissue. Breast Cancer Res Treat. 2003 Jan;77(2):157-65.

[xiv] Wapnir IL, Goris M, Yudd A, Dohan O, Adelman D, Nowels K, Carrasco N. The Na+/I- symporter mediates iodide uptake in
breast cancer metastases and can be selectively down-regulated in the thyroid. Clin Cancer Res. 2004 Jul 1;10(13):4294-302.
[xv] Somers SC Endocrine abnormalities in woman with breasst cancer. Lab Invest 1955; 4: 160-174.

[xvi] Buckwalter JA, Thomas GG. Selection of surgical treatment for well differentiated thyroid carcinomas. Ann Surg 1972; 176:
565.

[xvii] Moossa AR, Price-Evans DA, Brewer AC, Thyroid status and breast cancer: A new appraisal. Ann R Coll Surg Engl 1973;
53: 178-188.

[xviii] Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, Carrasco
N. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med. 2000 Aug;6(8):871-8.

[xix] Hoffman DA, McConahey WM. Breast Cancer Following Iodine-131 Therapy for Hyperthyroidism. JNCI 1983; 70: 63-67.

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