(G-261) Association of fibroglandular breast tissue characteristics from multiparametric MRI with cancer risk factors in women undergoing breast cancer screening

Breast cancer is the most common cancer diagnosed and second leading cause of cancer-related death among US women (1). There is an urgent need for improved risk assessment tools to tailor screening strategies to detect cancer earlier. Currently, cancer risk models, such as the Tyrer-Cuzick model, are used to estimate individual’s risk of developing breast cancer, incorporating patient factors such as age, breast density, menopausal status, and genetic mutations (2). Women at high risk of developing cancer usually receive annual breast screening,, often involving a magnetic resonance imaging (MRI) exam. MRI techniques, such as dynamic contrast-enhanced (DCE-) MRI or diffusion-weighted MRI (DWI) can reflect physiologic characteristics of breast tissue that precede or contribute to cancer risk. Background parenchymal enhancement (BPE), the degree of enhancement of fibroglandular tissue on DCE-MRI, has been shown to be associated with risk of developing breast cancer (3,4).  Moreover, DWI markers such as apparent diffusion coefficient (ADC, measuring the diffusivity of water molecules in tissue) and background parenchymal signal (BPS; persistent signal in fibroglandular tissue reflecting restricted water diffusion) can provide unique tissue microstructural information that may be related to cancer risk. In this study, we explore multiparametric MR features of normal breast tissue and their association with Tyrer-Cuzick risk scores in a population of women with dense breasts and at elevated risk of cancer. 

This IRB-approved study enrolled women with dense breasts and elevated breast cancer risk (personal or family history of breast cancer and/or BRCA mutation) scheduled to undergo a screening breast MRI from November 2019-September 2021 at our institution. Patient age, menopausal status and Tyrer-Cuzick lifetime risk scores were collected from medical records. Tyrer-Cuzick scores were binarized as high ( > 20%) or low (≤ 20%) risk (5).

Multiparametric breast MRI exams included DCE-MRI and DWI. DCE-MRI was obtained with one pre- and two post-contrast (acquired at 2min and 4min after injection of 0.1mmol/kg body-weight gadoteridol) scans. DWI was acquired with b-values 0/100/800/1200 s/mm². On DCE, BPE was qualitatively scored by the interpreting radiologist using subtraction images (first post-contrast minus pre-contrast) as minimal, mild, moderate, or marked. On DWI, BPS was similarly assessed by a radiologist from b=1200 s/mm² images and scored as minimal, mild, moderate, or marked. Quantitative ADC was calculated using custom software. Fig.1 includes images used for BPE and BPS assessments, as well as ADC measurements. Normal tissue was semiautomatically segmented on b=0 s/mm² image using fuzzy c-means clustering to obtain a fibroglandular tissue mask, and median ADC of the fibroglandular tissue was then calculated (from b-values 0/800 s/mm²).

Spearman’s rank correlation was used to evaluate the association between imaging metrics (BPE, ADC, and BPS), as well as the association between imaging metrics and patient age. Wilcoxon rank-sum test was used to compare imaging metrics of pre- vs. post-menopausal women, and of low vs. high Tyrer-Cuzick risk groups.

Our study enrolled 71 women with Tyrer-Cuzick risk scores available in their medical records (median age: 45, range 26-71), of which N=66 had menopausal status information available. The median Tyrer-Cuzick score for our cohort was 28.6, ranging from 4.33 to 85.6. BPS was positively correlated with BPE (rho=0.629, p< 0.01), and both BPS and BPE were negatively correlated with age (p< 0.01, Table 1). ADC was not significantly correlated with BPS, BPE or age. BPS and BPE were significantly lower in post-menopausal women compared to pre-menopausal women (p< 0.01, Table 2). No significant differences in ADC were observed between pre- vs. post-menopausal women. In comparison with Tyrer-Cuzick risk scores, women in the low-risk group showed significantly lower BPE compared to those in the high-risk group (Table 3, p< 0.01). No significant differences were observed between low and high-risk groups for DWI metrics of BPS or ADC.

Women with Tyrer-Cuzick risk scores above 20% showed higher BPE levels compared to low-risk (≤20%) women, suggesting that BPE may be able to stratify disease risk in women with dense breasts. Our study corroborates previous work that has shown an association of BPE with cancer risk using cancer outcome data (3,4). Our findings also show a close relationship between BPE and BPS within women with dense breasts, which has been reported previously in patients with invasive ductal carcinoma (6). Additionally, higher BPE and BPS were seen in younger and pre-menopausal women, further demonstrating an association with risk markers and reinforcing the potential for non-invasive, personalized MRI-based measures of cancer risk. Future work will investigate this association of BPE and BPS with patient outcomes (i.e., cancer or no cancer development) to further verify their utility as predictors of cancer risk.

We would like to thank our funding sources: NIH/NCI Grant R01CA207290 and NIH/NCI U01CA152637.

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