Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis

European Radiology https://doi.org/10.1007/s00330-023-09547-7 REVIEW Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta‑analysis Roxanne A. W. Ploumen1,2 · Cornelis M. de Mooij1,2,3 · Suzanne Gommers3 · Kristien B. M. I. Keymeulen1 · Marjolein L. Smidt1,2 · Thiemo J. A. van Nijnatten2,3 Received: 1 September 2022 / Revised: 23 December 2022 / Accepted: 23 February 2023 © The Author(s) 2023 Abstract Objectives In approximately 45% of invasive breast cancer (IBC) patients treated with neoadjuvant systemic therapy (NST), ductal carcinoma in situ (DCIS) is present. Recent studies suggest response of DCIS to NST. The aim of this systematic review and meta-analysis was to summarise and examine the current literature on imaging findings for different imaging modalities evaluating DCIS response to NST. More specifically, imaging findings of DCIS pre- and post-NST, and the effect of different pathological complete response (pCR) definitions, will be evaluated on mammography, breast MRI, and contrast-enhanced mammography (CEM). Methods PubMed and Embase databases were searched for studies investigating NST response of IBC, including information on DCIS. Imaging findings and response evaluation of DCIS were assessed for mammography, breast MRI, and CEM. A meta-analysis was conducted per imaging modality to calculate pooled sensitivity and specificity for detecting residual disease between pCR definition no residual invasive disease (ypT0/is) and no residual invasive or in situ disease (ypT0). Results Thirty-one studies were included. Calcifications on mammography are related to DCIS, but can persist despite complete response of DCIS. In 20 breast MRI studies, an average of 57% of residual DCIS showed enhancement. A meta-analysis of 17 breast MRI studies confirmed higher pooled sensitivity (0.86 versus 0.82) and lower pooled specificity (0.61 versus 0.68) for detection of residual disease when DCIS is considered pCR (ypT0/is). Three CEM studies suggest the potential benefit of simultaneous evaluation of calcifications and enhancement. Conclusions and Clinical Relevance Calcifications on mammography can remain despite complete response of DCIS, and residual DCIS does not always show enhancement on breast MRI and CEM. Moreover, pCR definition effects diagnostic performance of breast MRI. Given the lack of evidence on imaging findings of response of the DCIS component to NST, further research is demanded. Key Points • Ductal carcinoma in situ has shown to be responsive to neoadjuvant systemic therapy, but imaging studies mainly focus on response of the invasive tumour. • The 31 included studies demonstrate that after neoadjuvant systemic therapy, calcifications on mammography can remain despite complete response of DCIS and residual DCIS does not always show enhancement on MRI and contrast-enhanced mammography. * Roxanne A. W. Ploumen 1 Department of Surgery, Maastricht University Medical Centre+, Maastricht, The Netherlands 2 GROW – School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands 3 Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands 13 Vol.:(0123456789) European Radiology • The definition of pCR has impact on the diagnostic performance of MRI in detecting residual disease, and when DCIS is considered pCR, pooled sensitivity was slightly higher and pooled specificity slightly lower. Keywords Breast neoplasms · Carcinoma intraductal noninfiltrating · Neoadjuvant therapy · Diagnostic imaging · Systematic review Abbreviations CEM Contrast-enhanced mammography DCIS Ductal carcinoma in situ FN False negative FP False positive IBC Invasive breast cancer NST Neoadjuvant systemic therapy pCR Pathological complete response TN True negative TP True positive Introduction In recent decades, neoadjuvant systemic therapy (NST) has gained an increasing role in the treatment of both earlystage and locally advanced invasive breast cancer (IBC). The advantages of NST are in vivo evaluation of response to NST regimens and the decrease in tumour size, thereby increasing the likelihood of breast-conserving surgery and improving long-term outcomes [1–3]. Monitoring response to NST with the use of accurate imaging modalities is therefore important in surgical planning and estimation of prognosis [4]. Previous literature has indicated breast MRI is currently the most accurate imaging modality to monitor response of the primary tumour, yet a recent meta-analysis estimated similar accuracy of contrast-enhanced mammography (CEM) as well [5–9]. In approximately 45–60% of patients with IBC, a ductal carcinoma in situ (DCIS) component is present in the biopsy specimen at diagnosis [10–12]. DCIS has variable presentation, which hinders easy detection on imaging [13, 14]. On mammography, malignant calcifications or calcifications outside or adjacent to the mass can be considered suspicious for the presence of DCIS. However, 25% of DCIS cases do not contain mammographic calcifications [15, 16]. On breast MRI, DCIS tends to present as non-mass enhancement (NME); however, low-grade DCIS might lack enhancement [17, 18]. On CEM, DCIS can be detected based on the presence of enhancement and/or calcifications [19]. Many previous studies investigating response monitoring focused on predicting response of IBC rather than the presence of residual DCIS. Moreover, varying definitions for pathological complete response (pCR) are used in which residual DCIS is most often considered pCR [20]. On the 13 contrary, accurate detection of residual DCIS is relevant, as it can be a cause for recurrence [21]. It was previously assumed that DCIS responds poorly to NST [22]. However, recent retrospective studies have demonstrated that DCIS adjacent to IBC can be fully eradicated after NST [12, 23, 24]. Consequently, the need to monitor the response of DCIS to NST by imaging, in addition to IBC response assessment, has increased in order to improve surgical planning. Therefore, the aim of this systematic review and metaanalysis is to summarise and examine the current literature on imaging findings for different imaging modalities evaluating DCIS response to NST. More specifically, imaging findings of DCIS pre- and post-NST, and the effect of different pCR definitions, will be evaluated on mammography, breast MRI, and CEM. Materials and methods Literature search This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) statement [25]. PubMed and Embase databases were searched for eligible studies, and the last search was performed on August 9, 2022. Studies reporting mammography, breast MRI, and CEM results in predicting response to NST in the presence of IBC were included using the following keywords: breast neoplasm, ductal ca (...truncated)