Breast density is an independent risk factor for breast cancer. In digital mammography and digital breast tomosynthesis, breast density is assessed visually using the four-category scale developed by the American College of Radiology Breast Imaging Reporting and Data System (5th edition as of November 2022). Epidemiologically based risk models, such as the Tyrer-Cuzick model (version 8), demonstrate superior modeling performance when mammographic density is incorporated. Beyond just density, a separate mammographic measure of breast cancer risk is parenchymal textural complexity. With advancements in radiomics and deep learning, mammographic textural patterns can be assessed quantitatively and incorporated into risk models. Other supplemental screening modalities, such as breast US and MRI, offer independent risk measures complementary to those derived from mammography. Breast US allows the two components of fibroglandular tissue (stromal and glandular) to be visualized separately in a manner that is not possible with mammography. A higher glandular component at screening breast US is associated with higher risk. With MRI, a higher background parenchymal enhancement of the fibroglandular tissue has also emerged as an imaging marker for risk assessment. Imaging markers observed at mammography, US, and MRI are powerful tools in refining breast cancer risk prediction, beyond mammographic density alone.

While handcrafted radiomic features (HRFs) have shown promise in the field of personalized medicine, many hurdles hinder its incorporation into clinical practice, including but not limited to their sensitivity to differences in acquisition and reconstruction parameters. In this study, we evaluated the effects of differences in in-plane spatial resolution (IPR) on HRFs, using a phantom dataset (n = 14) acquired on two scanner models. Furthermore, we assessed the effects of interpolation methods (IMs), the choice of a new unified in-plane resolution (NUIR), and ComBat harmonization on the reproducibility of HRFs. The reproducibility of HRFs was significantly affected by variations in IPR, with pairwise concordant HRFs, as measured by the concordance correlation coefficient (CCC), ranging from 42% to 95%. The number of concordant HRFs (CCC > 0.9) after resampling varied depending on (i) the scanner model, (ii) the IM, and (iii) the NUIR. The number of concordant HRFs after ComBat harmonization depended on the variations between the batches harmonized. The majority of IMs resulted in a higher number of concordant HRFs compared to ComBat harmonization, and the combination of IMs and ComBat harmonization did not yield a significant benefit. Our developed framework can be used to assess the reproducibility and harmonizability of RFs.