Neoadjuvant breast cancer treatment response; tumor size evaluation through different conventional imaging modalities in the NeoDense study

Abstract

Background

Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imaging modalities and pathological complete response (pCR). Further, we investigated the agreement between these modalities pre-, during, and post-NACT, and the accuracy of predicting pathological residual tumor burden by these imaging modalities post-NACT.

Material and methods

This prospective Swedish cohort study included 202 BC patients assigned to NACT (2014–2019). Breast imaging with clinically used modalities: mammography, ultrasound, and tomosynthesis was performed pre-, during, and post-NACT. We investigated the agreement of tumor size by the different imaging modalities, and their accuracy of tumor size estimation. Patients with a radiological complete response or radiological partial response (≥30% decrease in tumor diameter) during NACT were classified as radiological early responders.

Results

Patients with an early radiological response by ultrasound had 2.9 times higher chance of pCR than early radiological non-responders; the corresponding relative chance for mammography and tomosynthesis tumor size measures was 1.8 and 2.8, respectively. Post-NACT, each modality, separately, could accurately estimate tumor size (within 5 mm margin compared to pathological evaluation) in 43–46% of all tumors. The diagnostic precision in predicting pCR post-NACT was similar between the three imaging modalities; however, tomosynthesis had slightly higher specificity and positive predictive values.

Conclusion

Breast imaging modalities correctly estimated pathological tumor size in less than half of the tumors. Based on this finding, predicting residual tumor size post-NACT is challenging using conventional imaging. Patients with early radiological non-response might need improved monitoring during NACT and be considered for changed treatment plans.

Keywords:

• Breast cancer
• neoadjuvant chemotherapy
• imaging
• response evaluation

Acknowledgements

The authors thank all the study participants. The authors acknowledge the outstanding work by research nurse Lina Zander. The authors thank the technicians, administrators, and radiologists at Unilabs Malmö and Helsingborg for their cooperation.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Regional Ethics Committee in Lund, Sweden (Official records number: 2014/13, 2014/521 and 2016/521).

Informed consent

Informed written consent was obtained from all participants included in the study.

Author contributions

IS contributed to the study design, made the study protocols, organized the enrollment of patients and the data/image collection, wrote the statistical plan, interpreted the data, solely drafted the manuscript (except for “Statistical analyses”), and organized the joint revision of the manuscript. DF delivered technical aid during image gathering, interpreted the data, and revised the manuscript. UH gave important input on the statistical plan, executed the statistical analyses, co-interpreted the data, co-wrote the “Statistical analyses” part of the manuscript, and substantially revised the manuscript. LR participated in data interpretation, and intellectually revised the manuscript. SZ partook in the over-all design of the study, interpreted the data, and contributed to the revision of the manuscript. SB was the foremost contributor to the initial design of the study, interpreted the data, and revised the manuscript. All authors have read and approved the final manuscript.

Disclosure statement

SZ: Speakers’ fees and travel support from Siemens Healthcare AG, and consultancy fees from Collective Minds Radiology AB. SB: Speakers’ fees from Pfizer, study-specific advisor Pfizer, and travel support from Roche. The other authors declare that they have no competing interests.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by grants from the Swedish Breast Cancer Group (BRO) and the Governmental Funding of Clinical Research within National Health Services.