Abstract
Neoadjuvant therapy (NAT) for breast cancer is a common treatment option in clinical practice. Tumor cellularity (TC), which represents the percentage of invasive tumors in the tumor bed, has been widely used to quantify the response of breast cancer to NAT. Therefore, automatic TC estimation is significant in clinical practice. However, existing state-of-the-art methods usually take it as a TC score regression problem, which ignores the ambiguity of TC labels caused by subjective assessment or multiple raters. In this paper, to efficiently leverage the label ambiguities, we proposed an Uncertainty-aware Label disTRibution leArning (ULTRA) framework for automatic TC estimation. The proposed ULTRA first converted the single-value TC labels to discrete label distributions, which effectively models the ambiguity among all possible TC labels. Furthermore, the network learned TC label distributions by minimizing the Kullback-Leibler (KL) divergence between the predicted and ground-truth TC label distributions, which better supervised the model to leverage the ambiguity of TC labels. Moreover, the ULTRA mimicked the multi-rater fusion process in clinical practice with a multi-branch feature fusion module to further explore the uncertainties of TC labels. We evaluated the ULTRA on the public BreastPathQ dataset. The experimental results demonstrate that the ULTRA outperformed the regression-based methods for a large margin and achieved state-of-the-art results. The code will be available from https://github.com/PerceptionComputingLab/ULTRA.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Key, T.J., Verkasalo, P.K., Banks, E.: Epidemiology of breast cancer. Lancet Oncol. 2(3), 133–140 (2001)
Thompson, A., Moulder-Thompson, S.: Neoadjuvant treatment of breast cancer. Ann. Oncol. 23, x231–x236 (2012)
Loibl, S., Denkert, C., von Minckwitz, G.: Neoadjuvant treatment of breast cancer-clinical and research perspective. Breast 24, S73–S77 (2015)
Rubovszky, G., Horváth, Z.: Recent advances in the neoadjuvant treatment of breast cancer. J. Breast Cancer 20(2), 119–131 (2017)
Rajan, R., et al.: Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response. Cancer: Interdisc. Int. J. Am. Cancer Soc. 100(7), 1365–1373 (2004)
Kumar, S., Badhe, B.A., Krishnan, K., Sagili, H.: Study of tumour cellularity in locally advanced breast carcinoma on neo-adjuvant chemotherapy. J. Clin. Diagn. Res.: JCDR 8(4), FC09 (2014)
Park, C.K., Jung, W.H., Koo, J.S.: Pathologic evaluation of breast cancer after neoadjuvant therapy. J. Pathol. Transl. Med. 50(3), 173 (2016)
Symmans, W.F., et al.: Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J. Clin. Oncol. 25(28), 4414–4422 (2007)
Smits, A.J., et al.: The estimation of tumor cell percentage for molecular testing by pathologists is not accurate. Mod. Pathol. 27(2), 168–174 (2014)
Madabhushi, A., Lee, G.: Image analysis and machine learning in digital pathology: challenges and opportunities. Med. Image Anal. 33, 170–175 (2016)
Tizhoosh, H.R., Pantanowitz, L.: Artificial intelligence and digital pathology: challenges and opportunities. J. Pathol. Inf. 9 (2018)
Peikari, M., Salama, S., Nofech-Mozes, S., Martel, A.L.: Automatic cellularity assessment from post-treated breast surgical specimens. Cytometry A 91(11), 1078–1087 (2017)
Geng, X.: Label distribution learning. IEEE Trans. Knowl. Data Eng. 28(7), 1734–1748 (2016)
Akbar, S., Peikari, M., Salama, S., Panah, A.Y., Nofech-Mozes, S., Martel, A.L.: Automated and manual quantification of tumour cellularity in digital slides for tumour burden assessment. Sci. Rep. 9(1), 1–9 (2019)
Rakhlin, A., Tiulpin, A., Shvets, A.A., Kalinin, A.A., Iglovikov, V.I., Nikolenko, S.: Breast tumor cellularity assessment using deep neural networks. In: Proceedings of the IEEE/CVF International Conference on Computer Vision Workshops (2019)
Akbar, S., Peikari, M., Salama, S., Nofech-Mozes, S., Martel, A.L.: Determining tumor cellularity in digital slides using ResNet. In: Medical Imaging 2018: Digital Pathology, vol. 10581, pp. 233–239. International Society for Optics and Photonics (2018)
He, K., Zhang, X., Ren, S., Sun, J.: Deep residual learning for image recognition. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 770–778 (2016)
Gao, B.B., Xing, C., Xie, C.W., Wu, J., Geng, X.: Deep label distribution learning with label ambiguity. IEEE Trans. Image Process. 26(6), 2825–2838 (2017)
Tang, Y., et al.: Uncertainty-aware score distribution learning for action quality assessment. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 9839–9848 (2020)
Wang, J., Geng, X.: Label distribution learning machine. In: International Conference on Machine Learning, pp. 10749–10759. PMLR (2021)
Wang, J., Geng, X., Xue, H.: Re-weighting large margin label distribution learning for classification. IEEE Trans. Pattern Anal. Mach. Intell. (2021)
Petrick, N., et al.: SPIE-AAPM-NCI BreastPathQ challenge: an image analysis challenge for quantitative tumor cellularity assessment in breast cancer histology images following neoadjuvant treatment. J. Med. Imaging 8(3), 034501 (2021)
Shrout, P.E., Fleiss, J.L.: Intraclass correlations: uses in assessing rater reliability. Psychol. Bull. 86(2), 420 (1979)
McHugh, M.L.: Interrater reliability: the kappa statistic. Biochemia Med. 22(3), 276–282 (2012)
Acknowledgments
This work was supported by the National Natural Science Foundation of China under Grant 62001144 and 62001141, and by Science and Technology Innovation Committee of Shenzhen Municipality under Grant JCYJ20210324131800002 and RCBS20210609103820029.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this paper
Cite this paper
Li, X., Liang, X., Luo, G., Wang, W., Wang, K., Li, S. (2022). ULTRA: Uncertainty-Aware Label Distribution Learning for Breast Tumor Cellularity Assessment. In: Wang, L., Dou, Q., Fletcher, P.T., Speidel, S., Li, S. (eds) Medical Image Computing and Computer Assisted Intervention – MICCAI 2022. MICCAI 2022. Lecture Notes in Computer Science, vol 13433. Springer, Cham. https://doi.org/10.1007/978-3-031-16437-8_29
Download citation
DOI: https://doi.org/10.1007/978-3-031-16437-8_29
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-16436-1
Online ISBN: 978-3-031-16437-8
eBook Packages: Computer ScienceComputer Science (R0)