Mammoscintigraphy in Patients with Aggressive Biological Subtypes of Breast Cancer: Assessment of Response to Neoadjuvant Chemotherapy

Purpose: To determine the diagnostic performance of mammoscintigraphy (SMG) with the ^99mTc-methoxy-isobutyl-isonitrile (^99mTc-MIBI) when used for assessment of the response to neoadjuvant chemotherapy (NACT) in patients with triple-negative and HER2-positive breast cancer (BC). Materials and methods: This retrospective study included 93 patients with morphologically verified triple-negative and HER2-positive breast cancer who received NACT between 2011 and 2018. Mammoscintigraphy was performed before treatment, after 2–3 and/or after 4–6 cycles of NACT. Diagnostic conclusions of SMG were compared with the results of morphological examination after surgical treatment at the end of NACT. The degree of pathological response to NACT was evaluated according to the Miller-Payne classification. Results: Overall, the sensitivity and specificity of SMG in predicting of complete pathologic tumor response after the completion of NACT were 83 % and 92 %, respectively. In patients with triple-negative and HER2-positive BC, sensitivity and specificity were 87 % and 92 %; 78 % and 91 %, respectively. When a complete scintigraphic response (grade V) was achieved after 2–3 cycles of NACT, the specificity and positive predictive value of SMG reached 100 % for both aggressive BC subtypes. Conclusions: The obtained results indicate the high diagnostic potential of SMG in predicting complete pathological tumor response to the NACT. Exceptional specificity and positive predictive value of SMG in the middle of the NACT make it promising tool in selection of BC patients for surgery de-escalation/elimination.

1. Kuerer HM, Valero V, Smith BD, et al. Selective Elimination of Breast Surgery for Invasive Breast Cancer: A Nonrandomized Clinical Trial. JAMA Oncol. 2025;11(5):529-34. https://doi.org/10.1001/jamaoncol.2025.0207. PMID: 40152443.

2. Novikov SN, Krivorotko P, Bryantseva Z, et al. Different approaches to target volume definition and boost delivery in surgery de-escalation clinical trial in breast cancer patients with pathological complete response. Radiat Oncol J. 2023;41(4):267-73. https://doi.org/10.3857/roj.2023.00528. PMID: 38185931.

3. I-SPY2 Trial Consortium, Yee D, DeMichele AM, et al. Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1355-62. https://doi.org/10.1001/jamaoncol.2020.2535. PMID: 32701140.

4. Shubeck SP, Morrow M, Dossett LA. De-escalation in breast cancer surgery. NPJ Breast Cancer. 2022;8(1):25. https://doi.org/10.1038/s41523-022-00383-4. PMID: 35197478.

5. Heil J, Schaefgen B, Sinn P, et al. Can a pathological complete response of breast cancer after neoadjuvant chemotherapy be diagnosed by minimal invasive biopsy? Eur J Cancer. 2016;69:142-50. https://doi.org/10.1016/j.ejca.2016.09.034. PMID: 27821317.

6. Baumgartner A, Tausch C, Hosch S, et al. Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients. Breast. 2018;39:19-23. https://doi.org/10.1016/j.breast.2018.02.028. PMID: 29518677.

7. Park J, Chae EY, Cha JH, et al. Comparison of mammography, digital breast tomosynthesis, automated breast ultrasound, magnetic resonance imaging in evaluation of residual tumor after neoadjuvant chemotherapy. Eur J Radiol. 2018;108:261-8. https://doi.org/10.1016/j.ejrad.2018.09.032. PMID: 30396666.

8. Mghanga FP, Lan X, Bakari KH, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography in monitoring the response of breast cancer to neoadjuvant chemotherapy: a meta-analysis. Clin Breast Cancer. 2013;13(4):271-9. https://doi.org/10.1016/j.clbc.2013.02.003. PMID: 23714689.

9. Romeo V, Accardo G, Perillo T, et al. Assessment and Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Comparison of Imaging Modalities and Future Perspectives. Cancers (Basel). 2021;13(14):3521. https://doi.org/10.3390/cancers13143521. PMID: 34298733.

10. Mankoff DA, Dunnwald LK, Gralow JR, et al. Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using [technetium 99m]-sestamibi scintimammography. Cancer. 1999;85(11):2410-23. PMID: 10357412.

11. Guo C, Zhang C, Liu J, et al. Is Tc-99m sestamibi scintimammography useful in the prediction of neoadjuvant chemotherapy responses in breast cancer? A systematic review and meta-analysis. Nucl Med Commun. 2016;37(7):675-88. https://doi.org/10.1097/MNM.0000000000000502. PMID: 26974314.

12. Kanaev SV, Novikov SN, Krivorotko PV, et al. Clinical significance of mammoscintigraphy results in breast cancer patients eceiving neoadjuvant polychemotherapy. Problems in Oncology. 2016;62(4):479-84. (In Russ.). https://doi.org/10.37469/0507-3758-2016-62-4-479-484.

13. Titskaya AA, Chernov VI, Sinilkin IG, et al. Standardized methods of radionuclide diagnostics. Mammoscintigraphy. Library of practical radiologist. Moscow, Zelenograd: LLC “NTC Amplituda”, 2014. 32 p. (In Russ.).

14. Titskaya AA, Chernov VI, Slonimskaya EM, et al. Mammoscintigraphy with 99mTc-MIBI in the Diagnosis of Breast Cancer. The Siberian Medical Journal. 2010;25(4-1):92-5. (In Russ.).

15. Kanaev SV, Krivorotko PV, Novikov SN, et al. About efficiency of mammoscintigraphy to determine the results of neoadjuvant polychemotherapy in breast cancer patients. Problems in Oncology. 2013;59(3):328-33. (In Russ.).

16. Novikov SN, Kanaev SV, Krivorotko PV, et al. Technetium-99m methoxyisobutylisonitrile scintimammography for monitoring and early prediction of breast cancer response to neoadjuvant chemotherapy. Nuclear Medicine Communications. 2015;36(8):795-801. https://doi.org/10.1097/MNM.0000000000000331. PMID: 26011586.

17. van der Voort A, Louis FM, van Ramshorst MS, et al. MRI-guided optimisation of neoadjuvant chemotherapy duration in stage II-III HER2-positive breast cancer (TRAIN-3): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2024;25(5):603-13. https://doi.org/10.1016/S1470-2045(24)00104-9. PMID: 38588682.

18. Collarino A, de Koster EJ, Valdés Olmos RA, et al. Is Technetium 99m Sestamibi Imaging Able to Predict Pathologic Nonresponse to Neoadjuvant Chemotherapy in Breast Cancer? A Meta-analysis Evaluating Current Use and Shortcomings. Clin Breast Cancer. 2018;18(1):9-18. https://doi.org/10.1016/j.clbc.2017.06.008. PMID: 28728876.

19. Zhang A, Li P, Liu Q. Breast-specific gamma camera imaging with 99mTc MIBI has better diagnostic performance than magnetic resonance imaging in breast cancer patients: a meta-analysis. Hell J Nucl Med. 2017;20(1):26-35. https://doi.org/10.1967/s002449910503. PMID: 28315905.

20. Kim S, Plemmons J, Hoang K, et al. Breast-Specific Gamma Imaging Versus MRI: Comparing the Diagnostic Performance in Assessing Treatment Response After Neoadjuvant Chemotherapy in Patients With Breast Cancer. AJR Am J Roentgenol. 2019;212(3):696-705. https://doi.org/10.2214/AJR.17.18930

21. Koelbel V, Pfob A, Schaefgen B, et al. Vacuum-Assisted Breast Biopsy After Neoadjuvant Systemic Treatment for Reliable Exclusion of Residual Cancer in Breast Cancer Patients. Ann Surg Oncol. 2022;29(2):1076-84. https://doi.org/10.1245/s10434-021-10847-9.

22. Tasoulis MK, Lee HB, Yang W, et al. Accuracy of Post-Neoadjuvant Chemotherapy Image-Guided Breast Biopsy to Predict Residual Cancer. JAMA Surg. 2020;155(12):e204103. https://doi.org/10.1001/jamasurg.2020.4103.

23. Hunt KN, Conners AL, Goetz MP, et al. Comparison of 99mTc Sestamibi Molecular Breast Imaging and Breast MRI in Patients With Invasive Breast Cancer Receiving Neoadjuvant Chemotherapy. AJR Am J Roentgenol. 2019;213(4):932-43. https://doi.org/10.2214/AJR.18.20628.

24. Menes TS, Golan O, Vainer G, et al. Assessment of Residual Disease With Molecular Breast Imaging in Patients Undergoing Neoadjuvant Therapy: Association With Molecular Subtypes. Clin Breast Cancer. 2016;16(5):389-95. https://doi.org/10.1016/j.clbc.2016.05.015.

25. Lee HS, Ko BS, Ahn SH, et al. Diagnostic performance of breast-specific gamma imaging in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2014;145(1):91-100. https://doi.org/10.1007/s10549-014-2920-z.

26.