Quantitative assessment of background parenchymal enhancement in breast MRI predicts response to risk-reducing salpingo-oophorectomy: preliminary evaluation in a cohort of BRCA1/2 mutation carriers

Abstract

Introduction: We present a fully automated method for deriving quantitative measures of background parenchymal enhancement (BPE) from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perform a preliminary evaluation of these measures to assess the effect of risk-reducing salpingo-oophorectomy (RRSO) in a cohort of breast cancer susceptibility gene 1/2 (BRCA1/2) mutation carriers.

Methods: Breast DCE-MRI data from 50 BRCA1/2 carriers were retrospectively analyzed in compliance with the Health Insurance Portability and Accountability Act and with institutional review board approval. Both the absolute (| |) and relative (%) measures of BPE and fibroglandular tissue (FGT) were computed from the MRI scans acquired before and after RRSO. These pre-RRSO and post-RRSO measures were compared using paired Student's t test. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the performance of relative changes in the BPE and FGT measures in predicting breast cancer that developed in these women after the RRSO surgery.

Results: For the 44 women who did not develop breast cancer after RRSO, the absolute volume of BPE and FGT had a significant decrease (P < 0.05) post-RRSO, whereas for the 6 women who developed breast cancer, there were no significant changes in these measures. Higher values in all BPE and FGT measures were also observed post-RRSO for the women who developed breast cancer, compared with women who did not. Relative changes in BPE percentage were most predictive of women who developed breast cancer after RRSO (P < 0.05), whereas combining BPE percentage and |FGT| yielded an AUC of 0.80, higher than BPE percentage (AUC = 0.78) or |FGT| (AUC = 0.66) alone (both P > 0.02).

Conclusions: Quantitative measures of BPE and FGT are different before and after RRSO, and their relative changes are associated with prediction of developing breast cancer, potentially indicative of women who are more susceptible to develop breast cancer after RRSO in BRCA1/2 mutation carriers.

Fig. 1

Illustration of our fully automated computer algorithm for quantifying magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) and fibroglandular tissue (FGT). Representative 2D and 3D tissue segmentations in selected breast MRI scans are shown. a A breast MRI slice of the T1-weighted sequence. b Segmentation of the whole breast (red contour) and FGT (green contour). c 3D display of FGT (green) relative to the whole breast (red). d This dynamic contrast-enhanced MRI subtraction (SUB) image corresponds to the T1 slice shown in (a). e BPE (purple contour) estimated over the FGT area in the SUB image. f 3D display of BPE (purple), FGT (green), and whole breast (red)

Fig. 2

Manhattan plot of the P value profiles of paired Student’s t test comparing the pre-RRSO and post-RRSO measures of background parenchymal enhancement (BPE) (both |BPE| and BPE %) computed by using a range of values (from 0 % to 100 %) for the R %_cutoff, indicating a range of the R %_cutoff values on which the difference between the pre-RRSO and post-RRSO BPE measures become significant (P < 0.05). RRSO, Risk-reducing salpingo-oophorectomy. a Results for the full cohort (i.e., a total of 50 women). b Results for the 44 women who did not develop breast cancer post-RRSO. c Results for the 6 women who developed breast cancer post-RRSO. Abbreviation: SUB, Subtraction image (i.e., post-contrast minus pre-contrast)

Fig. 3

The areas under the receiver operating characteristic curves (AUCs) of the predictive performance using relative changes in the different background parenchymal enhancement (BPE) measures across the entire range of R %_cutoff values were employed to predict women who developed breast cancer post-RRSO, where BPE % estimated from subtraction image 1 (i.e., post-contrast minus pre-contrast [SUB 1]) shows the highest predictive value (AUC 0.78, P = 0.09) for an R %_cutoff of 30 %

Fig. 4

Representative examples of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) from a magnetic resonance imaging (MRI) slice obtained pre-RRSO and post-RRSO in a woman who did not develop breast cancer after undergoing risk-reducing salpingo-oophorectomy (RRSO). FGT is circumscribed by green contours. BPE is estimated in both the first and third subtraction series (SUB 1 and SUB 3, respectively). This 40-year-old (at time of RRSO) woman had her pre-RRSO MRI at 6 months before RRSO and her post-RRSO MRI at 1 month after RRSO. She had no personal history of breast cancer or other cancer and had no breast cancer diagnosis for up to 9 years of post-RRSO follow-up. This example illustrates that there was a decrease of BPE and FGT after her RRSO. The volumetric pre-RRSO BPE % values were 1.5 % (SUB 1) and 6.5 % (SUB 3) and after RRSO, and BPE % values were 0.6 % (SUB 1) and 3.6 % (SUB 3)

Fig. 5

Representative examples of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) from a magnetic resonance imaging (MRI) slice obtained pre-RRSO and post-RRSO in a woman who developed breast cancer after undergoing risk-reducing salpingo-oophorectomy (RRSO). FGT is circumscribed by green contours. BPE is estimated in both the first and third subtraction series (SUB 1 and SUB 3, respectively). This 36-year-old (at time of RRSO) woman had her pre-RRSO MRI at 1 month before RRSO and her post-RRSO MRI at 6 months after RRSO. Breast cancer (ductal carcinoma in situ) was diagnosed in her right breast 6 years after RRSO, and her final pathologic examination showed in situ carcinoma with 2 foci of microinvasion (<0.1 cm). This example shows no decrease of BPE and FGT after RRSO. The volumetric pre-RRSO BPE % values were 10.7 % (SUB 1) and 10.6 % (SUB 3) and after RRSO, and BPE % values were 7.1 % (SUB 1) and 8.5 % (SUB 3)

Fig. 6

Area under the receiver operating characteristic curve (AUC) for the logistic regression models to predict women who developed breast cancer after risk-reducing salpingo-oophorectomy (RRSO), based on combination of relative changes (i.e., [post-RRSO − pre-RRSO]/pre-RRSO) of their absolute fibroglandular tissue (|FGT|) and background parenchymal enhancement first subtraction series (BPE % SUB 1) measures (i.e., best in Table 1). Combining BPE % and |FGT| yielded a higher AUC of 0.80 than that of BPE % (AUC 0.78) or |FGT| (AUC 0.66) alone (both P > 0.2)

Fig. 7

Whole-breast volume (|Breast|) changes after risk-reducing salpingo-oophorectomy (RRSO) showing a significant decrease for the 44 women who did not develop breast cancer post-RRSO but a non-significant increase for the 6 women who developed breast cancer after RRSO. The changes may be due to overall changes in the breast disuse, including changes in the fat content, induced by hormonal changes due to the RRSO surgery