Elastography and MRI for the Evaluation of Complete Response to Neoadjuvant Therapy for Breast Cancer

See also article by Wang and Huang et al in this issue.

Joao Vicente Horvat, MD, is a fellowship-trained radiologist specializing in breast imaging with 15 years of experience in the field. He is a senior associate consultant of the Division of Breast Imaging and Intervention at Mayo Clinic in Rochester, Minnesota. His research focuses on multimodality assessment of response to neoadjuvant treatment for breast cancer, lymph node evaluation, multiparametric breast MRI, high-risk lesions, molecular breast imaging, and contrast-enhanced mammography.

Robert T. Fazzio, MD, PhD, is a fellowship-trained radiologist specializing in breast imaging with 13 years of experience. He is a consultant and Division Chair of the Division of Breast Imaging and Intervention at Mayo Clinic in Rochester, Minnesota. Dr Fazzio’s research focuses on US elastography of breast tumors, high-resolution microvascular US with and without microbubble contrast material, and novel artificial intelligence approaches to detection and classification of breast cancer, as well as prediction of neoadjuvant therapy response.

The decrease in breast cancer morbidity and mortality is directly impacted by improvements in early diagnosis and treatment. Neoadjuvant therapy (NAT) has been increasingly used as the standard of care for presurgical treatment of many types of breast cancer, such as triple negative and human epidermal growth factor receptor 2–positive tumors. The neoadjuvant approach can quickly deliver systemic therapies that target the index malignancy and metastatic foci, with the objective of achieving pathologic complete response. NAT reduces cancer burden, decreases the extent of the disease, and renders tumors traditionally considered inoperable amenable to surgical excision (1). The use of NAT is a groundbreaking achievement in cancer treatment, proven to help reduce re-excision, recurrence, and mortality rates.

Imaging evaluation of response to therapy can provide the health care team with information on the efficacy of the medications administered and demonstrate to the surgeon the residual extent of disease that will require excision. Patients with favorable response can elect for shorter treatment or less extensive surgical excision, while patients with poor response to treatment may need to change the treatment regimen or undergo surgery earlier, thus avoiding unnecessary toxicity from ineffective treatment (2).

Different approaches are considered to treat residual disease at the tumor bed. Some institutions may consider pathologic complete response as absence of residual invasive or in situ disease after NAT, while others may consider complete response when absence of residual invasive disease is achieved. While the impact of residual in situ carcinoma on management and prognosis remains controversial, research studies that evaluate imaging response to NAT should investigate both situations.

Although mammography and B-mode breast US can be used to monitor response to NAT, the accuracy of both modalities alone in identifying residual disease is limited. Fibrosis and inflammatory changes that occur at the tumor bed in response to NAT may present as a persistent hypoechoic mass on US image or as a mass or asymmetry on mammogram. These posttreatment findings can have a similar appearance to the pretreatment examination, even in cases of pathologic complete response. Mammography may demonstrate persistence of calcifications at the tumor bed that are often a residual finding after NAT with variable clinical significance. These calcifications may even appear more numerous or extensive than on pretreatment mammogram, not reflecting the true treatment effect or the presence of residual disease (3). Considering residual calcifications at a tumor bed as residual disease after NAT may improve imaging sensitivity but will significantly decrease the specificity in detecting residual cancer.

Breast MRI is considered the standard of care modality for monitoring response to NAT given its high sensitivity and wide field of view. At MRI, the tumoral neovascularity is demonstrated by enhancement on dynamic contrast-enhanced sequences. Breast MRI is used before, during, and after NAT to assess tumor-related enhancement and its change over time in size and signal intensity caused by the systemic therapy (4). The tumor neovascularity can be disrupted by effective treatments, thus showing decrease or resolution of the enhancement after NAT. Breast MRI is not only able to assess the efficacy of NAT but can also delineate the size and extension of the lesion in the breast and evaluate for persistence or absence of infiltration to adjacent structures, such as the pectoral muscles, the nipple, and the skin. Furthermore, breast MRI has good accuracy in showing regional lymph node response to NAT during and following the course of treatment.

Although highly sensitive and effective, breast MRI has its limitations when used to monitor the efficacy of NAT. Occasionally, inflammatory changes at the tumor bed may present as persistent enhancement at MRI in cases of pathologic complete response, while fibrosis that disrupts tumoral vascularity may decrease or resolve the enhancement in patients with residual disease. Breast MRI has been shown to sometimes overestimate the extent of residual disease. MRI is also relatively more expensive than other modalities and is not always available when needed to evaluate NAT response (5). Therefore, studies that investigate ways to improve the imaging evaluation of response to NAT are of paramount importance.

US elastography has been used for many years in breast imaging, not only for the differentiation between benign and malignant lesions but also for predicting treatment response during and after NAT. Elastography methods may differ according to vendor and equipment model and are prone to operator-dependent variables that can affect radiologic interpretation. Shear-wave elastography, one of the most popular varieties of this approach, has been proven to evaluate tissue stiffness that may reflect tumor biology. Adding shear-wave elastography to B-mode US increases the usefulness of this modality in predicting disease response (6). For patients using only mammography and US for monitoring response, the addition of elastography may significantly improve the accuracy of the detection of complete response to NAT.

In this issue of Radiology: Imaging Cancer, the prospective study by Wang and Huang et al reports that shear-wave elastography has a high rate of accuracy in evaluating pathologic complete response after NAT, similar in performance to breast MRI for predicting absence of residual invasive disease and absence of residual invasive or in situ disease (7). This study included 224 patients who underwent both breast MRI and US with shear-wave elastography following NAT. The authors report that the combined model using both MRI and US with elastography had a superior performance than using either modality alone. These results suggest that implementing elastography for patients after NAT may be beneficial, demonstrating to the surgeon the presence or absence of residual disease, which may impact the surgical approach.

The present study highlights the usefulness of shear-wave elastography in the assessment of treatment response in patients receiving NAT. The authors report that this approach may lead to improved treatment outcomes, particularly when used in combination with MRI. The report from Wang and Huang et al acknowledges that breast MRI remains the most important imaging tool for clinical management in this patient population and identifies the need for studies with larger sample populations with patients from diverse backgrounds. Importantly, incorporating this approach into clinical workflows would be relatively straightforward given the accessibility of elastography on most modern US machines. Although the study from Wang and Huang et al focused on the breast tumor beds, there is enough evidence published stating that elastography may also show high accuracy in the evaluation of regional lymph nodes in patients with breast cancer (8). In the future, models that combine both breast tumor and axillary nodal evaluation after NAT may be investigated for their accuracy.

It is worth mentioning that patients who cannot undergo breast MRI examination may opt to undergo contrast-enhanced mammography (CEM) to evaluate response to NAT. CEM is a novel technique that uses iodinated contrast media to identify tumor neovascularity similarly to breast MRI. In recent studies, CEM has been demonstrated to have similar accuracy to MRI and may be an option for patients who are claustrophobic or have medical devices that are not safe for the MRI magnetic field (9). Models that include both CEM and US with elastography may in the future be investigated for their potential improved accuracy in comparison to either modality alone.

Molecular breast imaging (MBI) is a modality that has been increasingly used on screening and diagnostic scenarios. MBI uses intravenous administration of technetium 99 sestamibi to detect breast tumors. Published data have demonstrated that MBI can be used for the detection of pathologic complete response after NAT with similar performance to MRI. MBI has good accuracy in determining the extent of residual disease and may be an alternative for patients who cannot undergo MRI (10).

In conclusion, the study by Wang and Huang et al has reaffirmed the potential benefits of the routine use of elastography in breast imaging. Evaluation of presence or absence of complete response after NAT is extremely important, as it impacts patient management and surgical planning. The use of elastography improves the sonographic depiction of complete response after NAT and may be useful alongside breast MRI before surgical treatment.