Impact of short-term low-dose tamoxifen on molecular breast imaging background parenchymal uptake: a pilot study

Carrie B Hruska, Katie N Hunt, Amy Lynn Conners, Jennifer R Geske, Kathleen R Brandt, Amy C Degnim, Celine M Vachon, Michael K O'Connor, Deborah J Rhodes, Carrie B Hruska, Katie N Hunt, Amy Lynn Conners, Jennifer R Geske, Kathleen R Brandt, Amy C Degnim, Celine M Vachon, Michael K O'Connor, Deborah J Rhodes

Abstract

Background: High background parenchymal uptake (BPU) on molecular breast imaging (MBI) has been identified as a breast cancer risk factor. We explored the feasibility of offering a short-term intervention of low-dose oral tamoxifen to women with high BPU and examined whether this intervention would reduce BPU.

Methods: Women with a history of high BPU and no breast cancer history were invited to the study. Participants had an MBI exam, followed by 30 days of low-dose oral tamoxifen at either 5 mg or 10 mg/day, and a post-tamoxifen MBI exam. BPU on pre- and post-tamoxifen MBI exams was quantitatively assessed as the ratio of average counts in breast fibroglandular tissue vs. average counts in subcutaneous fat. Pre-tamoxifen and post-tamoxifen BPU were compared with paired t tests.

Results: Of 47 women invited, 22 enrolled and 21 completed the study (10 taking 5 mg tamoxifen, 11 taking 10 mg tamoxifen). Mean age was 47.7 years (range 41-56 years). After 30 days low-dose tamoxifen, 8 of 21 women (38%) showed a decline in BPU, defined as a decrease from the pre-tamoxifen MBI of at least 15%; 11 of 21 (52%) had no change in BPU (within ± 15%); 2 of 21 (10%) had an increase in BPU of greater than 15%. Overall, the average post-tamoxifen BPU was not significantly different from pre-tamoxifen BPU (1.34 post vs. 1.43 pre, p = 0.11). However, among women taking 10 mg tamoxifen, 5 of 11 (45%) showed a decline in BPU; average BPU was 1.19 post-tamoxifen vs. 1.34 pre-tamoxifen (p = 0.005). In women taking 5 mg tamoxifen, 2 of 10 (20%) showed a decline in BPU; average BPU was 1.51 post-tamoxifen vs.1.53 pre-tamoxifen (p = 0.99).

Conclusions: Short-term intervention with low-dose tamoxifen may reduce high BPU on MBI for some patients. Our preliminary findings suggest that 10 mg tamoxifen per day may be more effective than 5 mg for inducing declines in BPU within 30 days. Given the variability in BPU response to tamoxifen observed among study participants, future study is warranted to determine if BPU response could predict the effectiveness of tamoxifen for breast cancer risk reduction within an individual.

Trial registration: ClinicalTrials.gov NCT02979301 . Registered 01 December 2016.

Keywords: Background parenchymal uptake; Molecular breast imaging; Tamoxifen; Tc-99m sestamibi.

Conflict of interest statement

Ethics approval and consent to participate

This study was conducted under approval of our Institutional Review Board and was in compliance with the US Health Insurance Portability and Accountability Act. Informed written consent was obtained from all participants.

Consent for publication

Not applicable

Competing interests

CH and MO receive royalties for licensed technologies per agreement between Mayo Clinic and CMR Naviscan, a manufacturer of molecular breast imaging systems. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Quantitative BPU measured on pre-tamoxifen MBI and post-tamoxifen MBI for women taking 5 mg tamoxifen per day and 10 mg tamoxifen per day for 30 days
Fig. 2
Fig. 2
Mediolateral oblique views of the right breast from mammography (a) and MBI (b, c) obtained in a premenopausal study participant taking 5 mg tamoxifen per day for 30 days. The pre-tamoxifen MBI image (b) obtained on the first day of her menstrual cycle shows moderate background parenchymal uptake (BPU) with quantitative BPU of 1.9, corresponding to the areas of fibroglandular tissue on the mammogram. The post-tamoxifen MBI image (c), also obtained on the first day of menstrual cycle, shows minimal to mild BPU, with quantitative BPU of 1.3, a 31% decline from the pre-tamoxifen MBI

References

    1. Shermis RB, Wilson KD, Doyle MT, Martin TS, Merryman D, Kudrolli H, Brenner RJ. Supplemental breast cancer screening with molecular breast imaging for women with dense breast tissue. AJR Am J Roentgenol. 2016;207(2):450–457.
    1. Rhodes DJ, Hruska CB, Conners AL, Tortorelli CL, Maxwell RW, Jones KN, Toledano AY, O’Connor MK. Journal club: molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts. AJR Am J Roentgenol. 2015;204(2):241–251.
    1. Conners AL, Maxwell RW, Tortorelli CL, Hruska CB, Rhodes DJ, Boughey JC, Berg WA. Gamma camera breast imaging lexicon. AJR Am J Roentgenol. 2012;199(6):W767–W774.
    1. Hruska CB, Geske JR, Swanson TN, Mammel AN, Lake DS, Manduca A, Conners AL, Whaley DH, Scott CG, Carter RE, et al. Quantitative background parenchymal uptake on molecular breast imaging and breast cancer risk: a case-control study. Breast Cancer Res. 2018;20(1):46.
    1. Hruska CB, Rhodes DJ, Conners AL, Jones KN, Carter RE, Lingineni RK, Vachon CM. Background parenchymal uptake during molecular breast imaging and associated clinical factors. Am J Roentgenol. 2015;204(3):W363–W370.
    1. Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Schubert EK, Charlop AW, Tseng J, Rinn KJ, Livingston RB. [Tc-99m]-sestamibi uptake and washout in locally advanced breast cancer are correlated with tumor blood flow. Nucl Med Biol. 2002;29(7):719–727.
    1. Del Vecchio S, Salvatore M. 99mTc-MIBI in the evaluation of breast cancer biology. Eur J Nucl Med Mol Imaging. 2004;31(Suppl 1):S88–S96.
    1. Hruska CB, Scott CG, Conners AL, Whaley DH, Rhodes DJ, Carter RE, O’Connor MK, Hunt KN, Brandt KR, Vachon CM. Background parenchymal uptake on molecular breast imaging as a breast cancer risk factor: a case-control study. Breast Cancer Res. 2016;18(1):42.
    1. Hruska CB, Conners AL, Vachon CM, O’Connor MK, Shuster LT, Bartley AC, Rhodes DJ. Effect of menstrual cycle phase on background parenchymal uptake at molecular breast imaging. Acad Radiol. 2015;22(9):1147–56.
    1. Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97(22):1652–1662.
    1. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention? NPJ Breast Cancer. 2017;3(1):20.
    1. Decensi A, Gandini S, Serrano D, Cazzaniga M, Pizzamiglio M, Maffini F, Pelosi G, Daldoss C, Omodei U, Johansson H, et al. Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users. J Clin Oncol. 2007;25(27):4201–4209.
    1. Decensi A, Robertson C, Guerrieri-Gonzaga A, Serrano D, Cazzaniga M, Mora S, Gulisano M, Johansson H, Galimberti V, Cassano E, et al. Randomized double-blind 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in high-risk premenopausal women. J Clin Oncol. 2009;27(23):3749–3756.
    1. Guerrieri-Gonzaga A, Sestak I, Lazzeroni M, Serrano D, Rotmensz N, Cazzaniga M, Varricchio C, Pruneri G, Leonardi MC, Orecchia R, et al. Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS. Int J Cancer. 2016;139(9):2127–2134.
    1. de Sousa JA, Facina G, da Silva BB, Gebrim LH. Effects of low-dose tamoxifen on breast cancer biomarkers Ki-67, estrogen and progesterone receptors. Int Semin Surg Oncol. 2006;3(1):29.
    1. Goetz MP, Kamal A, Ames MM. Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther. 2008;83(1):160–166.
    1. Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst. 2011;103(9):744–752.
    1. Wu S, Weinstein SP, DeLeo MJ, 3rd, Conant EF, Chen J, Domchek SM, Kontos D. Quantitative assessment of background parenchymal enhancement in breast MRI predicts response to risk-reducing salpingo-oophorectomy: preliminary evaluation in a cohort of BRCA1/2 mutation carriers. Breast Cancer Res. 2015;17(1):67.
    1. King V, Brooks JD, Bernstein JL, Reiner AS, Pike MC, Morris EA. Background parenchymal enhancement at breast MR imaging and breast cancer risk. Radiology. 2011;260(1):50–60.
    1. King V, Kaplan J, Pike MC, Liberman L, David Dershaw D, Lee CH, Brooks JD, Morris EA. Impact of tamoxifen on amount of fibroglandular tissue, background parenchymal enhancement, and cysts on breast magnetic resonance imaging. Breast J. 2012;18(6):527–534.
    1. de Lima GR, Facina G, Shida JY, Chein MB, Tanaka P, Dardes RC, Jordan VC, Gebrim LH. Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer. 2003;39(7):891–898.
    1. Decensi A, Bonanni BD, Guerrieri-Gonzaga A, Gandini S, Robertson C, Johansson H, Travaglini R, Sandri MT, Tessadrelli A, Farante G, et al. Biologic activity of tamoxifen at low doses in healthy women. J Natl Cancer Inst. 1998;90(19):1461–1467.
    1. Sideras K, Ingle JN, Ames MM, Loprinzi CL, Mrazek DP, Black JL, Weinshilboum RM, Hawse JR, Spelsberg TC, Goetz MP. Coprescription of tamoxifen and medications that inhibit CYP2D6. J Clin Oncol. 2010;28(16):2768–2776.
    1. Sickles EA, D’Orsi CJ, Bassett LW. ACR BI-RADS® mammography. In: ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. 5. Reston: American College of Radiology; 2013.
    1. O’Connor MK, Hruska CB, Tran TD, Swanson T, Conners AL, Jones K, Rhodes DJ. Factors influencing the uptake of 99mTc-sestamibi in breast tissue on molecular breast imaging. J Nucl Med Technol. 2015;43(1):13–20.
    1. Hruska CB, Weinmann AL, Tello Skjerseth CM, Wagenaar EM, Conners AL, Tortorelli CL, Maxwell RW, Rhodes DJ, O’Connor MK. Proof of concept for low-dose molecular breast imaging with a dual-head CZT gamma camera. Part II. Evaluation in patients. Med Phys. 2012;39(6):3476–3483.
    1. Vachon CM, Suman VJ, Brandt KR, Kosel ML, Buzdar AU, Olson JE, Wu FF, Flickinger LM, Ursin G, Elliott CR, et al. Mammographic breast density response to aromatase inhibition. Clin Cancer Res. 2013;19(8):2144–2153.
    1. Kim J, Han W, Moon H-G, Ahn SK, Shin H-C, You J-M, Han S-W, Im S-A, Kim T-Y, Koo HR, et al. Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res. 2012;14(4):R102.
    1. Decensi A, Puntoni M, Guerrieri-Gonzaga A, Avino F, Cortesi L, Donadio M, Pacquola M, Falcini F, Gulisano M, Digennaro M, et al. GS3-01. A randomized placebo controlled phase III trial of low dose tamoxifen for the prevention of recurrence in women with operated hormone sensitive breast ductal or lobular carcinoma in situ. In: San Antonio Breast Cancer Symposium. San Antonio, TX: American Association for Cancer Research; 2018.
    1. Buckley MM, Goa KL. Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. Drugs. 1989;37(4):451–490.
    1. Lien EA, Johannessen DC, Aakvaag A, Lonning PE. Influence of tamoxifen, aminoglutethimide and goserelin on human plasma IGF-I levels in breast cancer patients. J Steroid Biochem Mol Biol. 1992;41(3–8):541–543.
    1. Decensi A, Robertson C, Viale G, Pigatto F, Johansson H, Kisanga ER, Veronesi P, Torrisi R, Cazzaniga M, Mora S, et al. A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. J Natl Cancer Inst. 2003;95(11):779–790.
    1. Kisanga ER, Gjerde J, Guerrieri-Gonzaga A, Pigatto F, Pesci-Feltri A, Robertson C, Serrano D, Pelosi G, Decensi A, Lien EA. Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial. Clin Cancer Res. 2004;10(7):2336–2343.
    1. Gjerde J, Gandini S, Guerrieri-Gonzaga A, Haugan Moi LL, Aristarco V, Mellgren G, DeCensi A, Lien EA. Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide. Breast Cancer Res Treat. 2012;134(2):693–700.
    1. Goetz MP, Ingle JN. CYP2D6 genotype and tamoxifen: considerations for proper nonprospective studies. Clin Pharmacol Ther. 2014;96(2):141–144.
    1. Binkhorst L, Mathijssen RHJ, Jager A, van Gelder T. Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping. Cancer Treat Rev. 2015;41(3):289–299.
    1. Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol. 2001;19(11):2797–2803.
    1. Dontchos BN, Rahbar H, Partridge SC, Korde LA, Lam DL, Scheel JR, Peacock S, Lehman CD. Are qualitative assessments of background parenchymal enhancement, amount of fibroglandular tissue on MR images, and mammographic density associated with breast cancer risk? Radiology. 2015;276(2):371–380.
    1. Arasu VA, Miglioretti DL, Sprague BL, Alsheik NH, Buist DSM, Henderson LM, Herschorn SD, Lee JM, Onega T, Rauscher GH, et al. Population-based assessment of the association between magnetic resonance imaging background parenchymal enhancement and future primary breast cancer risk. J Clin Oncol. 2019:JCO1800378 [Epub ahead of print].
    1. King V, Gu Y, Kaplan JB, Brooks JD, Pike MC, Morris EA. Impact of menopausal status on background parenchymal enhancement and fibroglandular tissue on breast MRI. Eur Radiol. 2012;22(12):2641–47.
    1. Delille JP, Slanetz PJ, Yeh ED, Kopans DB, Garrido L. Physiologic changes in breast magnetic resonance imaging during the menstrual cycle: perfusion imaging, signal enhancement, and influence of the T1 relaxation time of breast tissue. Breast J. 2005;11(4):236–241.
    1. King V, Goldfarb SB, Brooks JD, Sung JS, Nulsen BF, Jozefara JE, Pike MC, Dickler MN, Morris EA. Effect of aromatase inhibitors on background parenchymal enhancement and amount of fibroglandular tissue at breast MR imaging. Radiology. 2012;264(3):670–678.

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