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Effect of Menstrual Cycle Phase on Background Parenchymal Uptake at Molecular Breast Imaging

Posted Aug 31, 2015 Updated Apr 10, 2023
By Carrie B. Hruska PhD , Amy Lynn Conners MD , Celine M. Vachon PhD , Michael K. O'Connor PhD , Lynne T. Shuster MD , Adam C. Bartley MS , Deborah J. Rhodes MD
12 min read

Rationale and Objectives

The level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), termed background parenchymal uptake (BPU), has been anecdotally observed to fluctuate with menstrual cycle. Our objective was to assess the impact of menstrual cycle phase on BPU appearance.

Materials and Methods

Premenopausal volunteers who reported regular menstrual cycles and no exogenous hormone use were recruited to undergo serial MBI examinations during the follicular and luteal phase. A study radiologist, blinded to cycle phase, categorized BPU as photopenic, minimal mild, moderate, or marked. Change in BPU with cycle phase was determined, as well as correlations of BPU with mammographic density and hormone levels.

Results

In 42 analyzable participants, high BPU (moderate or marked) was observed more often in luteal phase compared to follicular ( P = .016). BPU did not change with phase in 30 of 42 participants (71%) and increased in the luteal phase compared to follicular in 12 (29%). High BPU was more frequent in dense breasts compared to nondense breasts at both the luteal (58% [15 of 26] vs. 13% [2 of 16], P = .004) and follicular phases (35% [9 of 26] vs. 6% [1 of 16], P = .061). Spearman correlation coefficients did not show any correlation of BPU with hormone levels measured at either cycle phase and suggested a weak correlation between change in BPU and changes in estrone and estradiol between phases.

Conclusions

We observed variable effects of menstrual cycle on BPU among our cohort of premenopausal women; however, when high BPU was observed, it was most frequently seen during the luteal phase compared to follicular phase and in women with dense breasts compared to nondense breasts.

Changes in radiologic appearance of the breast due to changes in hormonal milieu across phases of the menstrual cycle have been described for multiple imaging modalities, including mammography, magnetic resonance imaging (MRI), ultrasound, optical imaging, and nuclear medicine technologies . These menstrual cycle effects have important clinical implications. Timing imaging during the follicular phase of the menstrual cycle has been shown to improve diagnostic performance for both mammography and breast MRI . In addition, variation in the magnitude of cyclic changes on breast radiologic appearance between women is thought to reflect differences in hormonal responsiveness of breast tissue, which in turn has been hypothesized as a potential differentiator of breast cancer risk . By this theory, the more variant the appearance of the breast on imaging at different stages of the menstrual cycle, the more hormonally responsive the breast tissue and the higher the breast cancer risk.

Molecular breast imaging (MBI) is a functional imaging technique that uses a dedicated gamma camera to image preferential uptake of Tc-99m sestamibi in cells with elevated metabolic activity. MBI and similar techniques using Tc-99m sestamibi have been shown to detect breast tumors, particularly those occult on mammography because of radiographically dense tissue . MBI can also demonstrate uptake in normal parenchyma, which has been termed background parenchymal uptake (BPU) . In the screening setting, we have observed variability in BPU among women with similar mammographic densities, ranging from photopenic (less-intense uptake within fibroglandular tissue compared to that in subcutaneous fat) to marked (uptake in fibroglandular tissue more than twice as intense as that in fat), suggesting that MBI depicts properties of breast parenchymal function that are not readily appreciated by the anatomic depiction of fibroglandular tissue on mammography.

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Materials and Methods

Participants

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MBI Procedure

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Serum Hormone Measurements

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MBI Interpretation

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Data Analysis

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Results

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Table 1

Participant Characteristics of 42 Eligible Participants

Characteristic Mean, Median (Range) Age at enrollment (years) 41.0, 41.0 (35–45) Length of menstrual cycle (days) ∗ 28.1, 28.0 (24–34) Follicular-phase MBI Day of cycle 7.7, 7.5 (4–13) Estrone (pg/mL) 74.3, 69.0 (28–181) Estradiol (pg/mL) 116.6, 105.5 (29–307) Progesterone (ng/mL) 0.5, 0.4 (0.16–1.3) Testosterone (ng/mL) 24.0, 23.5 (12–37) SHBG (nmol/L) 48.5, 45.8 (18.8–102) FSH (mIU/L) 8.0, 7.5 (3.9–16.1) Luteal-phase MBI Day of cycle 22.4, 22.0 (19–31) Estrone (pg/mL) 94.7, 88.0 (25–175) Estradiol (pg/mL) 119.1, 110.0 (28–233) Progesterone (ng/mL) † 11.1, 10.9 (1.1–24.1) Testosterone (ng/mL) 23.2, 23.0 (10–45) SHBG (nmol/L) 54.1, 52.1 (22–114) FSH (mIU/L) 4.1, 4.0 (1.7–8.2) Mammographic density, ‡ n (%) Almost entirely fat 3 (7.1) Scattered fibroglandular densities 13 (31) Heterogeneously dense 22 (52) Extremely dense 4 (9.5)

FSH, follicle-stimulating hormone; MBI, molecular breast imaging; SHBG, sex hormone–binding globulin.

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Figure 1, Distribution of background parenchymal uptake at follicular and luteal phases of menstrual cycle for mammographically dense and nondense breasts. Note “jitter” in the y axis has been applied to reduce overplotting and allow visualization of individual data points.

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Figure 2, Mammography and molecular breast imaging (MBI) performed in a 41-year-old premenopausal woman demonstrating no change in background parenchymal uptake (BPU) with menstrual cycle. (a) Mammogram obtained within 1 month of MBI demonstrates heterogeneously dense tissue. Both follicular- (b) and luteal-phase MBI (c) demonstrate photopenic BPU of similar area and intensity.

Figure 3, Mammography and molecular breast imaging (MBI) performed in a 41-year-old premenopausal woman demonstrating an effect of menstrual cycle on background parenchymal uptake (BPU). (a) Mammogram obtained within 1 month of MBI demonstrates heterogeneously dense tissue. BPU was minimal mild on follicular-phase MBI (b) and changed to marked on luteal-phase MBI (c) .

Figure 4, Mammography and molecular breast imaging (MBI) performed in a 40-year-old premenopausal woman demonstrating a small effect of menstrual cycle on background parenchymal uptake (BPU). (a) Mammogram obtained within 1 month of MBI demonstrates heterogeneously dense tissue. BPU was categorized as marked on both follicular- (b) and luteal-phase MBI (c) ; however, when viewed together, BPU at luteal phase was interpreted as greater in area and intensity compared to BPU at follicular phase.

Figure 5, Mammography and molecular breast imaging (MBI) performed in a 36-year-old premenopausal woman. (a) Bilateral mediolateral oblique views from mammography demonstrate overall nondense breasts (breast imaging reporting and data system density category of almost entirely fat) with a ridge of benign dense tissue in upper left breast. Both follicular- (b) and luteal-phase MBI (c) demonstrated minimal mild background parenchymal uptake. However, uptake within the small area of dense tissue occurred only at luteal-phase MBI, giving the misleading appearance of a lesion. Subsequent negative mammography screening confirmed benignity of the area. (Color version of figure is available online.)

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Figure 6, Distribution of serum hormone levels, including (a) estrone, (b) estradiol, (c) progesterone, (d) testosterone, (e) SHBG, and (f) FSH, across background parenchymal uptake (BPU) levels at follicular and luteal phases of the menstrual cycle. Spearman correlation coefficients ( r ), given for all subjects ( N = 42) and for the subset with mammographically dense breasts ( N = 26), did not show significant correlation between any of the hormones and BPU category at either phase.

Figure 7, Distribution of the change in serum hormone levels, including (a) estrone, (b) estradiol, (c) progesterone, (d) testosterone, (e) SHBG, and (f) FSH, between cycle phases as a function of the change in background parenchymal uptake (BPU). BPU was considered as ordinal categories of 1, photopenic; 2, minimal mild; 3, moderate; and 4, marked, and the change in BPU was the difference of these assigned ordinal numbers between luteal and follicular phase. Spearman correlation coefficients ( r ), given for all subjects ( N = 42) and for the subset with mammographically dense breasts ( N = 26), showed a weak negative correlation between change in BPU category and change in two hormones: estrone and estradiol.

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Discussion

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