Breast Uptake of Radio-iodine in Differentiated Thyroid Cancer

A B S T R A C T

Radioiodine is often seen to accumulate within breast tissue in patients with differentiated thyroid cancer. Although the risk of secondary breast malignancy in patients with differentiated thyroid cancer treated with radioiodine is controversial, the identification and reduction of this uptake is prudent to minimize the radiation absorbed dose to the breast tissue. This article reviews the literature describing the etiology, frequency and patterns of radioiodine uptake in breast tissue. Approaches and techniques to help minimize the radioiodine uptake in lactating and nonlactating breasts are presented.

Keywords

Radioiodine, breast

Introduction

Radioiodine uptake in the breasts is frequently seen in radioiodine scanning done before and after radioiodine therapy for differentiated thyroid cancer. This article reviews the relevant literature regarding radioiodine activity within breasts, the cause and potential management of this uptake in patients with differentiated thyroid cancer. Despite the controversy regarding the increased risk of breast cancer related to radioiodine therapy, the uptake of radioiodine in the breasts is undesirable and must be minimized if possible, to reduce radiation exposure to the breasts. With a thorough understanding of the frequency, patterns, etiology, and mechanism of radioiodine breast uptake as well as the techniques to potentially reduce radioiodine uptake in the breast, the nuclear medicine physician, nuclear radiologist or endocrinologist can help decrease or even eliminate the uptake of radioiodine in the breast. This is turn may potentially reduce the radiation absorbed dose to the breast from 131-I therapies.

I Etiology of Radioiodine Uptake in Breasts

I-131 is used as a standard method of diagnosis and treatment for differentiated thyroid cancer. Multiple entities associated with breast uptake of radioiodine have been reported and include lactating breasts, hyperprolactinemia related conditions, localized pathologies like breast carcinoma, fibroadenomas, lactating breast with galactorrhea, mastitis and rarely metastatic disease to the breast from other malignancy such as thyroid carcinoma [1-16]. At times contamination, rib, lung, liver, soft tissue uptake and/or blood pool may at times be mistaken as breast activity [17].

i Sodium Iodide Symporter

The mechanism(s) of breast uptake of radioiodine has not been extensively evaluated. Sodium-iodide symporter (NIS) mediates uptake within thyroid gland and thyroid cancer. Similar expression has been demonstrated in extrathyroidal tissues and these organs are often seen as demonstrating physiological uptake within the radiodine scans. The normal human female breast epithelium expresses the sodium iodide symporter and can also organify iodide [18-20]. Over expression of Na-I symporter during lactation or in malignant conditions such as thyroid and breast cancer may be one of the most important mechanism of radioiodine uptake within the breasts. [5-9, 12, 21-24].

ii Prolactin

Some authors proposed the role of prolactin (PRL) causing iodine uptake within the human mammary cells. Barzowska suggested role of prolactin in radioiodine uptake in the lactation period [16]. PRL receptors are demonstrated in breast tissue and hyperprolactinemia had been proposed in some case reports even in nonlactating breasts [6, 25]. Animal studies have shown that PRL stimulation upregulates the expression of NIS (at both the mRNA and protein levels) in the normal lactating mammary gland, rendering these tissues capable of concentrating radioiodine. Expression of Na-I symporter may demonstrate cyclical changes and has been reported within the breast as a result of hormonal fluctuations and lactation as proposed by some authors[11, 12, 25, 26].

Ronga showed uptake of iodine in postmenopausal breast tissue in 2 patients with hyperprolactinemia [6]. The breast uptake was correlated to the high prolactin levels in both cases. In a previous study of 302 patients who underwent 131I WBS following radioiodine ablation of papillary or follicular thyroid carcinomas, breast tissue uptake was evident in only 4 cases [22]. One of the four patients had galactorrhea, and another had previously been treated with the antidopaminergic drug, sulpiride.

II Frequency and Pattern of Uptake

The literature reporting radioiodine uptake largely consists of case reports and case series and the frequency has not well reported. In a study of 302 patients who underwent 131I. WBS following radioiodine ablation of papillary or follicular thyroid carcinomas, breast tissue uptake was evident in only 4 cases [22]. Recently, Van Nostrand et al. reported that radioiodine administered for a whole-body scan in patients with well-differentiated thyroid cancer (WDTC) may localize in breast tissue in as many as 6% of patients, and this raises the possibility of delivering a significant, unintended radiation absorbed dose to breast tissue [27]. This was also previously reported by Hammami et al. [2].

Various patterns of breast uptake have been described, mainly categorized focal or diffuse dependent on the etiology. Focal or irregular or crescentic pattern of breast uptake is identified in localized breast pathology like breast carcinoma, fibroadenoma, fibrous dysplasia, lactating breasts, metastatic disease to the breast from other malignancy such as thyroid carcinoma. Diffuse pattern of breast uptake is identified in more global hormonal stimulation like lactating breast with galactorrhoea, hyperprolactinemia related conditions.

Bakheet and Hammani have described four patterns of uptake in postpartum breasts in twenty female patients one week after they stopped breast feeding: ‘full’, ‘focal’, ‘crescent’ and ‘irregular’ [2]. The full pattern represents diffuse intense uptake over the entire breast. Central, subareolar uptake gives a focal pattern of uptake, whereas more intense peripheral uptake represents a crescent. The fourth refers to irregular pattern of uptake and can mimic metastases. Thus, while full bilateral uptake is typically physiological, unilateral or irregular uptake was suggested to be highly suspicious for malignancy. Lactation usually causes uptake in bilateral breasts. Preferential lactation from one breast is a common occurrence among breast feeding mothers [26]. However, it can give rise to highly unusual and suspicious imaging appearances. In this case, unilateral uptake of I-131 was present in the right breast only as the patient had preferentially lactated only from the right side.

III Approach to Imaging

Diagnostic radioiodine imaging prior to ablative therapy may be of value in determining which patients may demonstrate excessive breast uptake of I-131 if radioiodine therapy is contemplated. The breast uptake can easily be distinguished by lateral images in most cases. In some instances, SPECT-CT may be used for confirming breast uptake at times particularly when diffuse to distinguish the uptake to be localized to lungs.

Barazowska demonstrated the utility of pretherapy imaging prior to radioiodine therapy and recommended I-123 as agent of choice for imaging [16]. In this study, a series of post-partum patients were imaged at varying time points postpartum, some using lactation inhibiting agents and I-123 scans were used to assess breast uptake. In the group with use of lactation inhibiting agents like bromocriptine or cabergoline, there was absent uptake as early as 3 weeks with their use and no patients demonstrated uptake beyond 14 weeks of their use. On the other hand, the 3 patients with no use, uptake was demonstrated as late as 32 weeks. No significant uptake was noted in one patient who did not initiate breast feeding. The author favored use of cabergoline over bromocriptine in suppressing breast activity. Another case report by Hsiao et al. documented the utility of radioiodine scan assessing for breast uptake prior to I-131 therapy to potentially prevent unnecessary radiation exposure to the breasts [3].

IV Proposed Management of Radioiodine Uptake

Some of the interventions are based on identifying the pattern and probable etiology for breast uptake. This would be as follows:

i If There is Diffuse Bilateral Breast Uptake

Evaluate for etiologies such as hyperprolactinemia, and lactation by gathering adequate clinical history.

ii Diffuse Unilateral Breast Uptake

Evaluate for clinical history related to mastitis with serosanguinous discharge or contamination. Preferential lactation history from that breast and mammogram information will be helpful.

iii Focal, Irregular or Crescentic Patterns of Bilateral Breast Uptake

Evaluate for benign breast conditions such as fibroadenoma, fibrous dysplasia or in some situations lobular pattern of uptake in lactation. Breast uptake related to primary breast malignancy or metastatic breast involvement from thyroid malignancy are possible bur rare.

V Approaches to Reduce Breast Uptake

Until further studies with a large patient numbers to evaluate the risk of breast malignancy from radiation exposure are performed, we believe that it is logical and prudent to identify and attempt to reduce radioiodine uptake in breast tissue observed on any pre-treatment radioiodine scan in order to limit the radiation absorbed dose to the breasts from any planned 131-I treatment. Unfortunately, there is little data in the literature regarding how the radioiodine breast uptake should be managed, and as a result, there has been no consistent management of this radioiodine breast uptake among our nuclear medicine physicians and endocrinologists. Each team of the interpreting nuclear medicine physician and endocrinologist have managed the patients independently, and the approaches have included (1) cancellation of the I-131 therapy, (2) postponement of the I-131 therapy for several months with or without repeat radioiodine scan before subsequent I-131 therapy, (3) postponement of I-131 treatment with repeat radioiodine scan of the breast performed during a different time of the menstrual period than when the first scan was performed, (4) postponement of the I-131 treatment with subsequent treatment with lactation inhibiting drugs such as cabergoline or (5) proceeding with the planned I-131 despite the significant uptake.

The approaches that have been used in attempts to decrease radioiodine uptake in breast tissue prior to 131-I therapy in our institution are several:
a. In lactating breast/postpartum conditions.
The approaches that have been used in attempts to decrease radioiodine uptake in breast tissue prior to 131-I therapy in our institution are several:
• In postpartum patients, wait for 3-6 months, and re-image with 123-I;
• Administer cabergoline 0.25 mg twice a week up to 1 mg twice a week for approximately 4 weeks based on prolactin level, and re-image with 123-I;
• Administer bromocriptine 7.5 mg twice a day for approximately 4 weeks and re-image.
b. Similarly, in a nonlactating non postpartum breast, we recommend treatment with cabergoline for 3-4 weeks and reevaluate with iodine scanning and proceeding with therapy. We may escalate the dose to achieve more suppression of breast uptake if adequate suppression is not achieved.
c. In cases of no definitive cause, either a trial of cabergoline or bromocriptine. Alternatively, no drug intervention and perform repeat imaging with 123-I in a different phase of menstrual cycle or 3-6 months later.

Summary

With a thorough understanding of the frequency, patterns, etiology, and mechanism of radioiodine breast uptake as well as the techniques to reduce false positive uptake and potentially reduce radioiodine uptake in the breast, the nuclear medicine physician, nuclear radiologist or endocrinologist can help decrease or even eliminate the uptake of radioiodine in the breast. This is turn may potentially reduce the radiation absorbed dose to the breast from 131-I therapies. Despite the controversy regarding the increased risk of breast cancer related to radioiodine therapy, the uptake of radioiodine in the breasts is undesirable and must be minimized if possible, to reduce radiation exposure to the breasts.

Funding

None.

Acknowledgement

Some content has been presented as Educational exhibits at the Society of Nuclear Medicine National meetings. It has however not been published in review or a substantially similar form (in print or electronically, including on a web site).

Article Info

Article Type

Review Article

Publication history

Received: Mon 25, May 2020
Accepted: Mon 08, Jun 2020
Published: Tue 23, Jun 2020

Copyright

© 2023 Kanchan Kulkarni. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.RDI.2020.02.08

Author Info

Kanchan Kulkarni

Corresponding Author

Kanchan Kulkarni
Medstar Medical Group Radiology, Medstar Washington Hospital Center, Division of Nuclear Medicine, Washington, D.C., USA

Figures & Tables

References

1. M M Hammami, S Bakheet (1996) Breast uptake in non-breast-feeding women: clinical and scintigraphic characteristics. J Nucl Med 37: 26-31. [Crossref]
2. S M Bakheet, M M Hammami (1994) Patterns of radioiodine uptake by the lactating breast. Eur J Nucl Med 21: 604-608. [Crossref]
3. Edward Hsiao, Thien Huynh, Robert Mansberg, George Bautovich, Paul Roach (2004) Diagnostic I-123 scintigraphy to assess potential breast uptake of I-131 before radioiodine therapy in a postpartum woman with thyroid cancer. Clin Nuc Med 29: 498-501. [Crossref]
4. Orsolya Dohán, Antonio De la Vieja, Viktoriya Paroder, Claudia Riedel, Mona Artani et al. (2003) The Sodium/Iodide Symporter (NIS): Characterization, Regulation and Medical Significance. Endocr Rev 24: 48-77. [Crossref]
5. W R Hedrick, R N Di Simone, R L Keen (1986) Radiation dosimetry from breast milk excretion of radioiodine and pertechnetate. J Nucl Med 27: 1569-1571. [Crossref]
6. Giuseppe Ronga, Rocco Bruno, Efisio Puxeddu, Filippo Calcinaro, Teresa Montesano et al. (2007) Radioiodine uptake in non-lactating mammary glands: Evidence for a causative role of hyperprolactinemia. Thyroid 17: 363-366. [Crossref]
7. Rillema JA, Yu TX, Jhiang SM (2000) Effect of prolactin on sodium iodide symporter expression in mouse mammary gland explants. Am J Physiol Endocrinol Metab 279: E769-E772. [Crossref]
8. J Y Cho, R Léveillé, R Kao, B Rousset, A F Parlow et al. (2000) Hormonal regulation of radioiodide uptake activity and Na-I symporter expression in mammary glands. J Clin Endocrinol Metab 85: 2936-2943. [Crossref]
9. E G Zalis, R B Ellison, O Barrett Jr (1965) A diagnostic pitfall with radioiodine scanning. Am J Roentgenol Radium Ther Nucl Med 94: 837-838. [Crossref]
10. G R Baeumler, K G Joo (1986) Radioactive iodine uptake by breasts. J Nucl Med 27: 149-151. [Crossref]
11. S M Bakheet, J Powe, M M Hammami (1998) Unilateral radioiodine breast uptake. Clin Nucl Med 23:170-171. [Crossref]
12. T Kogai, K Taki, G A Brent (2006) Enhancement of sodium-iodide symporter expression in thyroid and breast cancer.  Endocr Relat Cancer 13: 797-826. [Crossref]
13. U H Tazebay, I L Wapnir, O Levy, O Dohan, L S Zuckier et al. (2000) The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 6: 871-888. [Crossref]
14. F Berger, S Unterholzner, J Diebold, P Knesewitsch, K Hahn et al. (2006) Mammary radioiodine accumulation due to functional sodium iodide symporter expression in a benign fibroadenoma. Biochem Biophys res commun 349: 1258-1263. [Crossref]
15. B A Eskin, J A Parker, J G Bassett, D L George (1974) Human breast uptake of radioiodine. Obstet Gynecol 44: 398-402. [Crossref]
16. Malgorzata Brzozowska, Paul J Roach (2006) Timing and potential role of diagnostic I-123 scintigraphy in assessing radioiodine breast uptake before ablation in postpartum women with thyroid cancer. A case series. Clin Nuc Med 31: 683-687. [Crossref]
17. S Bakheet, M M Hammami (1993) Spurious Lung Metastastases on Radioiodine Thyroid and Whole Body Imaging. Clin Nuc Med 18: 307-312.  [Crossref]    
18. C Spitzweg, W Joba, W Eisenmenger, A E Heufelder (1998) Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of complimentary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 83: 1746-1751. [Crossref]
19. P L Welcsh, D A Mankoff  (2000) Taking up iodine in breast tissue. Nature 406: 688-689. [Crossref]
20. S Filetti, J M Bidart, F Arturi, B Caillou, D Russo (1999) Sodium-iodide symporter: a key transport system in thyroid cancer cell metabolism.  Eur J Endocrinol 141: 443-457. [Crossref]
21. F Arturi, D Russo, M Schlumberger, J A du Villard, B Caillou et al. (1998) Iodide symporter gene expression in human thyroid tumors. J Clin Endocrinol Metab 83: 2493-2496. [Crossref]
22. R Bruno, P Giannasio, G Ronga, E Baudin, J P Travagli et al. (2004) Sodium iodide symporter expression and radioiodine distribution in extrathyroidal tissues. J Endocrinol Invest 7: 1010-1014. [Crossref]
23. Franco Arturi, Elisabetta Ferretti, Ivan Presta, Tiziana Mattei, Angela Scipioni et al. (2005) Regulation of iodide uptake and sodium-iodide symporter expression in the MCF-7 breast cancer cell line. J Clin Endocrinol Metab 90: 2321-2326. [Crossref]
24. S M Bakheet, J Powe, M M Hammami (1997) Radioiodine uptake in the chest. J Nucl Med 38: 984-986. [Crossref]
25. P Perros, U K Mallick, J D Fenwick (2003) Radioiodine Uptake in Normal Female Breasts and Liver of a Patient with Differentiated Thyroid Cancer Imaged by Whole Body Scanning. Thyroid 13: 511. [Crossref]
26. A Sinha, K M Bradley, J Steatham, A Weaver (2008) Asymmteric breast uptake of radioiodine in a patient with thyroid malignancy: metastases or not? J R Soc Med 101: 319-320. [Crossref]
27. Douglas Van Nostrand, Martha Aiken, Frank Atkins, Shari Moreau, C Garcia et al. (2009 ) The utility of radioiodine scans prior to 131-I ablation in patients with well-differentiated thyroid cancer.   Thyroid 19: 849-855. [Crossref]