RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer

Abstract

Although approximately 70% of breast cancer patients demonstrate a clinical response on neoadjuvant systemic therapy on physical examination or on anatomic radiographic imaging, only 3%-40% achieve a pathologic complete response (pCR). Magnetic resonance imaging (MRI) is superior to physical examination, ultrasound, and mammography in response evaluation during neoadjuvant systemic therapy. The accuracy of breast MRI to predict pCR has a moderate sensitivity, but high specificity. The accuracy of anatomic imaging to assess residual disease and predict pCR depended on anatomic radiographic imaging cancer subtypes. Response monitoring using breast is accurate in triple-negative or HER2-positive tumors. It was inaccurate in estrogen receptor-positive/HER2-negative subtype. Another approach currently under investigation is dynamic contrast-enhanced MRI and diffusion weighted-imaging, (18)F-fluorodeoxyglucose positron emission tomography, fluorodeoxyglucose positron emission tomography/computed tomography.

Neoadjuvant Model as a Platform for Research in Breast Cancer and Novel Targets under Development in this Field

“…Both trials showed a similar cRR and pCR rate with NET and CT, although in the second trial there was a trend for worse outcome in the endocrine arm for premenopausal patients and those with high Ki67. The longer NET in the second trial was consistent with data from non-randomized series [14,15] suggesting that longer treatment could yield increased CR and higher CS rates beyond those achieved by 3 or 4 months of therapy; therefore, 6 months is now the minimum period recommended for NET and the standard approach in current trials. In light of all the above, NET for at least 6 months appears to be a reasonable alternative to CT for postmenopausal women with stage II and III BC with luminal A characteristics, while for premenopausal women NET still remains investigational.…”

Imaging Considerations and Interprofessional Opportunities in the Care of Breast Cancer Patients in the Neoadjuvant Setting

“…59 Although ultrasound has many advantages, according to revised RECIST 1.1 guidelines, ultrasound examinations should not be used in clinical trials to measure tumor regression or progression of lesions because the examination is subjective and operator dependent. 17 Ultrasound has been evaluated for its ability to assess tumor burden prior to surgery. 60,61 Roubidoux et al demonstrated that in tumors larger than 7 mm, ultrasound has 100% sensitivity for assessing response to NAT, with an overall sensitivity of 87%.…”

“…Current standard-of-care assessment of treatment response in solid tumors during clinical trials is based on the Response Evaluation Criteria in Solid Tumors (RECIST), which evaluates the changes in the longest dimension of a tumor with MRI. 17 However, biological, molecular, and vascular alterations that occur within the tumor prior to downstream changes in tumor size can be described by advanced imaging modalities and early imaging biomarkers of response to treatment.…”

Neoadjuvant Trials in ER+ Breast Cancer: A Tool for Acceleration of Drug Development and Discovery

“…Table 4 summarizes clinical trials investigating the clinical utility of Ki67 and PEPI scores. As this table shows, many ongoing studies include clinical overall response rate (ORR) as primary end-point, We recognize, however, that the validity of ORR using radiological methods, such as ultrasound, mammography or magnetic resonance imaging, as endpoint for the efficacy of NET trials has been limited (70). Further, ORR has failed to predict clinical outcome (71).…”