Eur Radiol (2012) 22:2641–2647 DOI 10.1007/s00330-012-2553-8
BREAST
Impact of menopausal status on background parenchymal enhancement and fibroglandular tissue on breast MRI Valencia King & Yajia Gu & Jennifer B. Kaplan & Jennifer D. Brooks & Malcolm C. Pike & Elizabeth A Morris
Received: 21 March 2012 / Revised: 10 May 2012 / Accepted: 11 May 2012 / Published online: 4 July 2012 # European Society of Radiology 2012
Abstract Objective To evaluate the effect of menopausal status on the background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on breast MRI. Methods Retrospective review identified 1,130 women who underwent screening breast MRI between July and November 2010. In 28 of these women, breast MRI was performed both at one time point while pre- and one time point while postmenopausal (median interval 49 months). Two independent readers blinded to menopausal status used categorical scales to rate BPE (minimal/mild/moderate/marked) and FGT (fatty/ scattered/heterogeneously dense/dense). Consensus was reached when there was disagreement. The sign test was used V. King : J. B. Kaplan : E. A. Morris Department of Radiology, Breast Imaging Section, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA J. D. Brooks : M. C. Pike Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, New York, NY 10065, USA Y. Gu Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China Y. Gu Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China V. King (*) Department of Radiology, Memorial Sloan-Kettering Cancer Center, Evelyn H. Lauder Breast Center, #715, 300 East 66th Street, New York, NY 10065, USA e-mail:
[email protected]
to assess changes in rating categories, and the Spearman rank and Fisher’s exact tests were used to measure correlations and associations between variables. Results Significant proportions of women demonstrated decreases in BPE and FGT on post-menopausal breast MRI (P00.0001 and P00.0009). BPE category was unchanged in 39 % (11/28) and decreased in 61 % (17/28) of women. FGT category was unchanged in 61 % (17/28) and decreased in 39 % (11/28) of women. Age, reason for menopause, or interval between MRIs had no significant impact on changes in BPE and FGT. Conclusion On MRI, BPE, and FGT decrease after menopause in significant proportions of women; BPE decreases more than FGT. Key Points • On MRI, background parenchymal enhancement and fibroglandular tissue both decrease after menopause. • The reduced postmenopausal enhancement is more marked in parenchyma than fibroglandular tissue. • Background enhancement and fibroglandular tissue seen on MRI are under hormonal influence. Keywords Breast . MRI . Enhancement . Fibroglandular tissue . Menopause Abbreviations BPE background parenchymal enhancement FGT fibroglandular tissue
Introduction Background enhancement of normal breast parenchyma on breast MRI is a well-known phenomenon that occurs after intravenous contrast medium administration [1–3]. Historically, it has been seen as an undesirable feature of normal
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breast tissue, as it was thought to decrease the specificity of breast MRI and increase the likelihood of a recommendation for short-term follow-up [4]. However, recent studies have suggested that enhancement of the normal breast parenchyma may play a role in breast cancer risk prediction [5], and also in treatment response and outcome assessment [6]. Although it has been postulated that background parenchymal enhancement (BPE) on breast MRI is related to vascular supply and permeability, the precise causes of the differences in enhancement between and within individuals during their lifetimes are not well understood. Evidence suggests that hormonally sensitive physiological changes that occur in the breasts may be reflected in variations in normal BPE that occur with the menstrual cycle [1, 3] and with age [3]. Studies have shown that enhancement is lowest in week 2 and higher in weeks 1 and 4 of the menstrual cycle [1], and have suggested that BPE is highest between ages 35 and 50 [3]. Normal parenchymal enhancement on breast MRI has also been shown to increase in women taking menopausal hormone therapy [7, 8] and decrease in women taking selective oestrogen receptor modulators, such as raloxifene [9] or toremifene [10], supporting the theory that BPE is hormonally sensitive. Although the relationships between BPE and week of menstrual cycle, age, and hormonal therapies have been investigated, to the best of our knowledge nothing is known about the impact of menopause on the amount of BPE. Although one might hypothesise that after menopause, BPE should decrease concomitantly with the expected decrease in estrogenic hormone activity, this hypothesis has never been tested. Given recent research linking the level of BPE to breast cancer risk [5] and linking changes in BPE to breast cancer treatment response and outcome [6], it is important to understand if and how BPE changes with menopause. Because BPE occurs within normal fibroglandular tissue (FGT) on MRI, it is also important to relate changes in the level of BPE to changes in the amount of FGT at menopause. The purpose of our study was therefore to evaluate the effect of menopausal status on the level of BPE and the amount of FGT on breast MRI.
Materials and methods Patients The institutional review board granted a waiver of authorisation and patient consent for our retrospective study, which was compliant with the Health Insurance Portability and Accountability Act (HIPAA). The study was conducted using a pairedobservation design. To be included, a woman had to have undergone breast MRI at our institution at least once while pre-menopausal and at least once while post-menopausal. To
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ensure that any BPE changes with menopause were not confounded by other factors that might influence BPE, any woman with a current or previous history of breast cancer, history of breast radiation between the two study MRI examinations, or taking menopausal hormone or antihormonal therapy (such as tamoxifen, raloxifene, or an aromatase inhibitor) or other chemotherapy at the time of either breast MRI was excluded. Retrospective review of our imaging database identified 1,130 women with two or more contrast-enhanced breast MRIs at our institution with one of the examinations between July and November 2010. Of these, 800 women with a current or previous history of breast cancer were excluded, leaving 330 eligible. Twenty-eight of these women had undergone breast MRI both while pre-menopausal and while post-menopausal, and were not on menopausal hormone replacement, anti-hormonal therapy, or chemotherapy at the time of either breast MRI. None of the patients had a history of breast radiation treatment between the two breast
Table 1 Patient characteristics during breast MRI studies carried out before and after menopause Characteristic
Pre-menopause Post-menopause
Age range (years) Mean Median Weight (kg) (range) Mean Median Body mass index (kg/m2) (range)a Mean
34-53 45 45 47-100 67 64 17.5–39.9 24.8
37-59 49 52 48-95 68 68 18.3–38.7 25.1
Median Interval between MRIs (months) (range) Mean Median Oral contraceptive pills (in pre-menopausal patients) Not used within 6 months Never Risk factors BRCA 1/2 mutation positive Atypia at prior biopsy LCIS at previous biopsyb Papilloma at previous biopsy History of mediastinal irradiation Family history of breast cancer Family history of ovarian cancer Family history of other cancer
23 12-92
24
53 49
16 12 3 5 6 2 1 23 6 10
a
Body mass index not available in four women
b
LCIS lobular carcinoma in situ
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Fig. 1 Woman at familial and genetic risk of breast cancer who had a risk-reducing oophorectomy. (a) Breast MRI before menopause demonstrates marked background parenchymal enhancement on a sagittal T1weighted fat-suppressed contrastenhanced maximum intensity projection (MIP) subtraction image and (b) a contrast-enhanced T1-weighted fat-suppressed MIP image after menopause demonstrates mild background parenchymal enhancement
MRI examinations. To maximise the time between the MRI examinations and the time when the women were transitioning through menopause, the earliest pre-menopausal and the most recent post-menopausal breast MRIs were used for this study (median interval between MRI examinations, 49 months, range 12–92 months). Patient characteristics including age, medication history, surgical history, menstrual and menopausal status, and risk factors for breast cancer/indication of MRI screening were recorded from the electronic medical record and also from patient data forms completed at the time of breast MRI (Table 1). MRI image evaluation All breast MRI examinations were performed with the patient prone, using a dedicated surface breast coil. All premenopausal patients were imaged at 1.5 Tesla (T). Of the post-menopausal breast MRI examinations, 20 were done at 1.5 T and 8 were done at 3 T. Thus for most women (71 %) the same field strength was used for both the pre- and postmenopausal MRI. The standard imaging protocol included a Fig. 2 Woman with a family history of breast and ovarian cancer. (a) A sagittal T1weighted non-fat-suppressed unenhanced image before menopause demonstrates a moderate amount of fibroglandular tissue and (b) a T1-weighted non-fat-suppressed unenhanced image after menopause demonstrates a mild amount of fibroglandular tissue
localising sequence followed by sagittal fat-suppressed T2weighted, non-fat-suppressed T1-weighted, and T1-weighted bilateral simultaneous sagittal fat-suppressed sequences before and three times after a rapid bolus injection of 0.1 mmol/l of gadopentetate dimeglumine (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, NJ, USA) per kg of body weight through an in-dwelling intravenous catheter. Sequence acquisition parameters have been previously reported [11]. Section thickness was 3 mm. After the examination, the unenhanced images were subtracted from the first contrast-enhanced images on a pixel-by-pixel basis. All images were independently and individually reviewed for level of BPE and amount of FGT by two fellowship-trained breast imaging radiologists (with 2 years and 10 years of experience in breast MRI), who were blinded as to whether the MRI examinations had been done before or after menopause. Before reviewing any breast MRIs for the study, both readers reviewed a standard training set of 20 non-study cases demonstrating categorical levels of BPE and FGT. BPE was visually assessed for the entire breast parenchyma, using a combination of pre- and post-contrast fat-suppressed
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Fig. 3 Bar chart illustrating numbers of women with minimal, mild, moderate, and marked background parenchymal enhancement (BPE) before and after menopause
T1-weighted and subtraction images. Both the volume and intensity of enhancement were considered in the global assessment of BPE and categorised based on proposed Breast Imaging Reporting and Data System (BI-RADS) criteria as minimal, mild, moderate, or marked [2]. The amount of FGT, defined as any non-fat, non-cystic breast parenchyma, was visually assessed using a combination of T2-weighted and non-fat and fat-suppressed T1-weighted images. The amount of FGT was evaluated based on American College of Radiology BI-RADS criteria as minimal (fatty, 75 %) [12]. Figures 1 and 2 are examples of cases in which decreases in BPE and FGT were seen, respectively. Statistical analysis The sign test was used to assess changes in the rating categories for BPE and FGT between pre- and post-menopausal breast MRI examinations. The Pearson chi-squared and Fisher’s exact tests were used to test associations between categorical variables. Spearman’s rank correlation test was used to describe the relationship between changes in BPE and changes in FGT, and also between changes in BPE and FGT and age after menopause and duration of time between MRIs. All statistical significance levels quoted (P values) are two sided. All statistical analyses were done using the statistical package Stata 11 (StataCorp, College Station, TX, USA).
Results BPE and menopause We found that BPE was higher in pre-menopausal than postmenopausal women (P00.0001, Fig. 3) such that marked BPE was present in 14 % (4/28) of pre-menopausal women versus 4 % (1/28) of post-menopausal women, and minimal BPE was present in 54 % (15/28) of post-menopausal women versus only 14 % (4/28) of pre-menopausal women. After menopause, BPE decreased in 17 of the 28 women (61 %) (Table 2). BPE decreased by one assessment level in 36 % (10/ 28), two levels in 21 % (6/28), and three levels in 4 % (1/28) of women. No increases in BPE were observed. Excluding the eight women in whom the breast MRI after menopause was done at 3 T did not alter the proportion of women with a decrease in BPE [60 % (12/20), P00.002]. The impact of the reason for menopause on changes in BPE was also examined. Twenty-three women underwent natural menopause (defined as cessation of menses in the absence of surgery or medical ovarian suppression), and five underwent menopause because of a bilateral oophorectomy. Of those women who underwent menopause because of an oophorectomy, two had minimal BPE on the pre-menopausal breast MRI, with no potential for a further category decrease with menopause. The three remaining women had decreases in BPE after oophorectomy (2 women by 2 levels and 1 woman by 1 level). Amongst the women who underwent natural menopause, BPE remained stable in 39 % (9/23) and
Inter-reader agreement
Table 2 Changes in background parenchymal enhancement (BPE) between pre- and post-menopausal women
Agreement between readers (inter-reader) for BPE and FGT were evaluated by kappa statistics. Strength of kappa agreement was defined as
