Abstract

BackgroundMolecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Additionally, MBI depicts variable levels of background parenchymal uptake (BPU) within nonmalignant, dense fibroglandular tissue. We investigated whether BPU is a risk factor for breast cancer.MethodsWe conducted a retrospective case-control study of 3027 eligible women who had undergone MBI between February 2004 and February 2014. Sixty-two incident breast cancer cases were identified. A total of 179 controls were matched on age, menopausal status, and MBI year. Two radiologists blinded to case status independently assessed BPU as one of four categories: photopenic, minimal to mild, moderate, or marked. Conditional logistic regression analysis was performed to estimate the associations (OR) of BPU categories (moderate or marked vs. minimal to mild or photopenic) and breast cancer risk, adjusted for other risk factors.ResultsThe median age was 60.2 years (range 38–86 years) for cases vs. 60.2 years (range 38–88 years) for controls (p = 0.88). Women with moderate or marked BPU had a 3.4-fold (95 % CI 1.6–7.3) and 4.8-fold (95 % CI 2.1–10.8) increased risk of breast cancer, respectively, compared with women with photopenic or minimal to mild BPU, for two radiologists. The results were similar after adjustment for BI-RADS density (OR 3.3 [95 % CI 1.6–7.2] and OR 4.6 [95 % CI 2.1–10.5]) or postmenopausal hormone use (OR 3.6 [95 % CI 1.7–7.7] and OR 5.0 [95 % CI 2.2–11.4]). The association of BPU with breast cancer remained in analyses limited to postmenopausal women only (OR 3.8 [95 % CI 1.5–9.3] and OR 4.1 [95 % CI 1.6–10.2]) and invasive breast cancer cases only (OR 3.6 [95 % CI 1.5–8.8] and OR 4.4 [95 % CI 1.7–11.1]). Variable BPU was observed among women with similar mammographic density; the distribution of BPU categories differed across density categories (p < 0.0001).ConclusionsThis study provides the first evidence for BPU as a risk factor for breast cancer. Among women with dense breasts, who comprise >40 % of the screening population, BPU may serve as a functional imaging biomarker to identify the subset at greatest risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0704-6) contains supplementary material, which is available to authorized users.

Highlights

  • Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts

  • Risk models developed within the Breast Cancer Surveillance Consortium (BCSC) have incorporated American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) breast density categories [8], a genetic risk score, and history of benign breast disease; yet, c-statistics, or AUC, remain

  • background parenchymal uptake (BPU) was associated with BI-RADS density in that the distribution of BPU categories differed across density categories overall (p < 0.0001), and among cases for one reader, and among controls for both readers (p < 0.001), as shown Fig. 3

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Summary

Introduction

Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Supplemental screening options capable of detecting mammographically occult cancers are increasingly being offered to women with dense breasts [3,4,5]. BPU was qualitatively assessed per breast according to a validated lexicon for gamma imaging of the breast as one of four categories: photopenic, minimal to mild, moderate, or marked (Fig. 1) [19]. During the course of routine clinical practice, mammographic density was subjectively assessed according to ACR BI-RADS density categories (fourth edition) by breast imaging radiologists [8]. Percentage density was measured on right and left craniocaudal mammograms from either digitized film or “for presentation” digital mammograms in Digital Imaging and Communications in Medicine format

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