Clinical Radiology 70 (2015) 706e710
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics M.Y. Kim a, *, N. Choi a, J.-H. Yang b, Y.B. Yoo b, K.S. Park b a b
Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, South Korea Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, South Korea
article in formation Article history: Received 6 October 2014 Received in revised form 5 February 2015 Accepted 20 February 2015
AIM: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. MATERIALS AND METHODS: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. RESULTS: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p¼0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogenreceptor (ER)-positive breast cancer (p¼0.045) and progesterone receptor (PR)-positive breast cancer (p¼0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p¼0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (þ)/HER2 () cancer (OR¼0.231, 95% CI: 0.070, 0.760; p¼0.016). No association between the histological tumour characteristics and BPE was observed. CONCLUSION: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction At mammography, breast density refers to the opaque area on a mammogram representing the fibroglandular * Guarantor and correspondent: M.Y. Kim, Department of Radiology, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 143-914, South Korea. Tel.: þ82 2 2030 5514; fax: þ82 2 2030 5549. E-mail address: [email protected] (M.Y. Kim).
tissues of the breast. Breast density is a strong risk factor for breast cancer, and women with mammographically dense breasts have three- to five-times higher risk of breast cancer than women with mammographically fatty breasts.1e6 Also, many studies have reported that breast density has been positively associated with tumour size, involvement of axillary lymph node, and stage even if tumour detection is delayed by masking effects in women with dense breasts.7e12
http://dx.doi.org/10.1016/j.crad.2015.02.017 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
M.Y. Kim et al. / Clinical Radiology 70 (2015) 706e710
Similar to breast density at mammography, the level of background parenchymal enhancement (BPE) at breast MRI after contrast material administration are features of normal breast tissue. Based on visual assessment, BPE is usually classified into the following four categories: minimal, mild, moderate, and marked.13 BPE does not correlate with mammographic breast density (MGD),14 and these parameters are reduced in postmenopausal women as compared with premenopausal women.15 Regarding breast cancer risk, in a caseecontrol study by King et al.,16 moderate or marked BPE is associated with significantly greater odds of breast cancer than minimal or mild BPE when patients with breast cancer are compared with control subjects.16 This raises a question of whether there is an association between BPE at MRI and breast cancer. Characterising the association between BPE and tumour characteristics may enhance our understanding of how BPE influences breast cancer risk. To the authors’ knowledge, there has been no report regarding the relationship between background parenchymal features and primary tumour characteristics. Therefore, the purpose of the present study was to investigate the relationship between MGD and BPE at breast MRI and histopathological features of invasive breast cancers.
Material and methods Patient selection and clinicopathological data collection This study was approved by the institutional review board, and the requirement for informed consent was waived. A retrospective search of radiological computer records and electronic medical records at Konkuk University Medical Center identified 210 women diagnosed with unilateral invasive ductal carcinoma consecutively between January 2013 and December 2013, who had pre-treatment breast MRI and mammography of the unaffected breast, were not taking hormonal therapy, and did not have a prior history of breast cancer. Women with unknown menopausal state (n¼24) or with tumours of unknown receptor status or tumour grade (n¼8) were excluded. As a result, 178 women were included in the study. The patients’ medical records were reviewed to identify the clinical symptoms (e.g., the presence of a palpable mass). The pathological reports were also reviewed to determine tumour size, histological grade, hormone receptor status (oestrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2 [HER2]) and the presence of nodal metastases. The ER, PR, and HER2 statuses were determined by immunohistochemical analysis. For the immunohistochemical analysis, formalin-fixed, paraffin-embedded tissue sections were immunohistochemically stained. The Allred score was used to determine the ER and PR statuses. The results were classified as positive when the total score, expressed as the sum of the proportion and immuno-intensity scores, was 3 or more. The intensity of the c-erbB-2 staining was scored as 0, 1þ, 2þ, or 3þ. Tumours with a 3þ score were classified
707
as HER2-positive, and tumours with a 0 or 1þ score were classified as negative. In tumours with a 2þ score, gene amplification using SISH (silver in-situ hybridisation) was used to determine the HER2 status. HER2 expression was considered positive if the ratio of HER2 gene copies to chromosome 17 signals was >2.
Technique Digital mammography was performed using a Selenia system (Lorad, Bedford, CT, USA). Standard two-view mammography (mediolateral oblique and craniocaudal) was performed with additional views as necessary. The MRI examinations were performed using a 3 T MRI system (Signa HDxt; General Electric Medical Systems, Milwaukee, WI, USA) with a dedicated eight-channel breast coil. Simultaneous bilateral acquisition was used. After obtaining a transverse localiser image, sagittal fatsuppressed T2-weighted fast spin-echo images were obtained. Dynamic contrast-enhanced MRI examinations included one pre-contrast and five post-contrast, sagittal image acquisitions using a fat-suppressed T1-weighted three-dimensional (3D) fast spoiled gradient-recalled echo sequence with parallel volume imaging. Delayed contrastenhanced 3D fast spoiled gradient-echo images with fat suppression in the axial plane were also obtained. Gadoterate meglumine (Dotarem; Guerbet, Aulnay-Sous-Bois, France) was injected into the ante-cubital vein using an automated injector (Spectris Solaris, Medrad Europe, Maastricht, The Netherlands) at a dose of 0.1 mmol/kg of body weight and at a rate of 3 ml/s followed by a 20 ml saline flush. The MRI images used for analysis in this study were maximum intensity projections of the subtracted images of the first post-contrast image stack of dynamic series.
Mammography and breast MRI interpretation and coding of breast density and background parenchymal enhancement All mammograms and MRI studies were retrospectively reviewed by two experienced breast imaging radiologists with 5 and 9 years of experience (M.Y.K. and N.C.) in consensus without knowledge of the clinicopathological findings of the cases. MGD was graded as 1 ¼ almost entirely fat (75% glandular).17 For each breast MRI examination, the BPE of the entire breast parenchyma was visually assessed by maximal intensity projections and was defined as enhancement of the normal breast parenchyma. The volume and intensity of enhancement in the contralateral breast were considered in the global assessment of BPE and categorised as minimal, mild, moderate or marked 13(Fig 1).
Statistical analysis At breast MRI, MGD and BPE were dichotomised for analyses; MGD was divided into low MGD (category1 or 2) and high MGD (category 3 or 4) and BPE was divided into low
708
M.Y. Kim et al. / Clinical Radiology 70 (2015) 706e710
BPE (minimal or mild) and high BPE (moderate or marked). At breast MRI MGD and BPE were analysed using Spearman’s rank correlation coefficient. To investigate whether MGD and BPE at breast MRI were associated with histopathological features of invasive breast cancers, logistic regression analyses were used, adjusting for age and menopausal status (pre-versus postmenopausal). Variables with p
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics M.Y. Kim a, *, N. Choi a, J.-H. Yang b, Y.B. Yoo b, K.S. Park b a b
Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, South Korea Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, South Korea
article in formation Article history: Received 6 October 2014 Received in revised form 5 February 2015 Accepted 20 February 2015
AIM: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. MATERIALS AND METHODS: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. RESULTS: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p¼0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogenreceptor (ER)-positive breast cancer (p¼0.045) and progesterone receptor (PR)-positive breast cancer (p¼0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p¼0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (þ)/HER2 () cancer (OR¼0.231, 95% CI: 0.070, 0.760; p¼0.016). No association between the histological tumour characteristics and BPE was observed. CONCLUSION: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction At mammography, breast density refers to the opaque area on a mammogram representing the fibroglandular * Guarantor and correspondent: M.Y. Kim, Department of Radiology, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 143-914, South Korea. Tel.: þ82 2 2030 5514; fax: þ82 2 2030 5549. E-mail address: [email protected] (M.Y. Kim).
tissues of the breast. Breast density is a strong risk factor for breast cancer, and women with mammographically dense breasts have three- to five-times higher risk of breast cancer than women with mammographically fatty breasts.1e6 Also, many studies have reported that breast density has been positively associated with tumour size, involvement of axillary lymph node, and stage even if tumour detection is delayed by masking effects in women with dense breasts.7e12
http://dx.doi.org/10.1016/j.crad.2015.02.017 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
M.Y. Kim et al. / Clinical Radiology 70 (2015) 706e710
Similar to breast density at mammography, the level of background parenchymal enhancement (BPE) at breast MRI after contrast material administration are features of normal breast tissue. Based on visual assessment, BPE is usually classified into the following four categories: minimal, mild, moderate, and marked.13 BPE does not correlate with mammographic breast density (MGD),14 and these parameters are reduced in postmenopausal women as compared with premenopausal women.15 Regarding breast cancer risk, in a caseecontrol study by King et al.,16 moderate or marked BPE is associated with significantly greater odds of breast cancer than minimal or mild BPE when patients with breast cancer are compared with control subjects.16 This raises a question of whether there is an association between BPE at MRI and breast cancer. Characterising the association between BPE and tumour characteristics may enhance our understanding of how BPE influences breast cancer risk. To the authors’ knowledge, there has been no report regarding the relationship between background parenchymal features and primary tumour characteristics. Therefore, the purpose of the present study was to investigate the relationship between MGD and BPE at breast MRI and histopathological features of invasive breast cancers.
Material and methods Patient selection and clinicopathological data collection This study was approved by the institutional review board, and the requirement for informed consent was waived. A retrospective search of radiological computer records and electronic medical records at Konkuk University Medical Center identified 210 women diagnosed with unilateral invasive ductal carcinoma consecutively between January 2013 and December 2013, who had pre-treatment breast MRI and mammography of the unaffected breast, were not taking hormonal therapy, and did not have a prior history of breast cancer. Women with unknown menopausal state (n¼24) or with tumours of unknown receptor status or tumour grade (n¼8) were excluded. As a result, 178 women were included in the study. The patients’ medical records were reviewed to identify the clinical symptoms (e.g., the presence of a palpable mass). The pathological reports were also reviewed to determine tumour size, histological grade, hormone receptor status (oestrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2 [HER2]) and the presence of nodal metastases. The ER, PR, and HER2 statuses were determined by immunohistochemical analysis. For the immunohistochemical analysis, formalin-fixed, paraffin-embedded tissue sections were immunohistochemically stained. The Allred score was used to determine the ER and PR statuses. The results were classified as positive when the total score, expressed as the sum of the proportion and immuno-intensity scores, was 3 or more. The intensity of the c-erbB-2 staining was scored as 0, 1þ, 2þ, or 3þ. Tumours with a 3þ score were classified
707
as HER2-positive, and tumours with a 0 or 1þ score were classified as negative. In tumours with a 2þ score, gene amplification using SISH (silver in-situ hybridisation) was used to determine the HER2 status. HER2 expression was considered positive if the ratio of HER2 gene copies to chromosome 17 signals was >2.
Technique Digital mammography was performed using a Selenia system (Lorad, Bedford, CT, USA). Standard two-view mammography (mediolateral oblique and craniocaudal) was performed with additional views as necessary. The MRI examinations were performed using a 3 T MRI system (Signa HDxt; General Electric Medical Systems, Milwaukee, WI, USA) with a dedicated eight-channel breast coil. Simultaneous bilateral acquisition was used. After obtaining a transverse localiser image, sagittal fatsuppressed T2-weighted fast spin-echo images were obtained. Dynamic contrast-enhanced MRI examinations included one pre-contrast and five post-contrast, sagittal image acquisitions using a fat-suppressed T1-weighted three-dimensional (3D) fast spoiled gradient-recalled echo sequence with parallel volume imaging. Delayed contrastenhanced 3D fast spoiled gradient-echo images with fat suppression in the axial plane were also obtained. Gadoterate meglumine (Dotarem; Guerbet, Aulnay-Sous-Bois, France) was injected into the ante-cubital vein using an automated injector (Spectris Solaris, Medrad Europe, Maastricht, The Netherlands) at a dose of 0.1 mmol/kg of body weight and at a rate of 3 ml/s followed by a 20 ml saline flush. The MRI images used for analysis in this study were maximum intensity projections of the subtracted images of the first post-contrast image stack of dynamic series.
Mammography and breast MRI interpretation and coding of breast density and background parenchymal enhancement All mammograms and MRI studies were retrospectively reviewed by two experienced breast imaging radiologists with 5 and 9 years of experience (M.Y.K. and N.C.) in consensus without knowledge of the clinicopathological findings of the cases. MGD was graded as 1 ¼ almost entirely fat (75% glandular).17 For each breast MRI examination, the BPE of the entire breast parenchyma was visually assessed by maximal intensity projections and was defined as enhancement of the normal breast parenchyma. The volume and intensity of enhancement in the contralateral breast were considered in the global assessment of BPE and categorised as minimal, mild, moderate or marked 13(Fig 1).
Statistical analysis At breast MRI, MGD and BPE were dichotomised for analyses; MGD was divided into low MGD (category1 or 2) and high MGD (category 3 or 4) and BPE was divided into low
708
M.Y. Kim et al. / Clinical Radiology 70 (2015) 706e710
BPE (minimal or mild) and high BPE (moderate or marked). At breast MRI MGD and BPE were analysed using Spearman’s rank correlation coefficient. To investigate whether MGD and BPE at breast MRI were associated with histopathological features of invasive breast cancers, logistic regression analyses were used, adjusting for age and menopausal status (pre-versus postmenopausal). Variables with p
