br Keywords br Breast br Cancer br MRI
Purpose: To evaluate the distribution of MRI breast parenchymal enhancement (BPE) among different breast cancer subtypes searching for any significant difference in terms of immunohistochemical and receptorial pat-terns (Estrogen Receptor -ER, Progesterone Receptor - PR, Human Epidermal Growth Factor Receptor 2 - HER2). Methods: 82 consecutive patients affected by breast cancer underwent breast DCE-MRI. Two radiologists ret-rospectively evaluated all subtracted MR enhanced images for classifying BPE. ER, PR and HER2 expression was assessed by immunohistochemical analysis. ER and PR status was evaluated using Allred score (positive values: score ≥3). The intensity of the cerbB-2 staining was scored as 0, 1+, 2+, or 3+ (positive values: ≥ 3+; negative:0 and 1+; 2+ value assessed with silver in-situ hybridization). Patients were classified into five ca-tegories based on cancer subtypes: Luminal A, Luminal B HER2 negative, Luminal B HER2 positive, HER2 positive non luminal, triple negative. The χ2 test was used for evaluating the significance of BPE type dis-tribution into the five groups of tumor subtypes and the distribution of the five breast cancer subtypes among every single BPE type. The correlation of BPE with factors such as age, menopausal status and lesion diameter was investigated using multivariate regression analysis and logistic regression. Cohen's kappa statistics was used in order to assess inter-observer agreement for classifying BPE.
Conclusions: BPE could play a crucial role as an imaging bridge to molecular breast cancer subtype allowing an additional risk stratification in the field of breast MRI and targeted screening tests. Luminal B (HER2-) tumors could prevail in case of mild BPE on CE-MRI examinations and TN tumors in patients with marked BPE. Further studies on larger series are needed to confirm this hypothesis.
Both normal and abnormal breast tissue enhances after DiD perchlorate material intravenous injection at magnetic resonance imaging (MRI), but the morphology and the dynamic enhancement features represent the basis for breast cancer detection.
Background Parenchymal Enhancement (BPE) is defined as the en-hancement of normal breast tissue at contrast enhanced MRI dynamic studies [1–10].
Several authors found no correlation between BPE and mammo-graphic density [11–14], but other studies reported that increased BPE was associated with greatly increased risk of breast cancer in high risk
Corresponding author at: D.E.T.O., Breast Unit, University of Bari Medical School, Piazza Giulio Cesare 11, 70124, Bari, Italy. E-mail address: [email protected] (M. Moschetta).
G. Dilorenzo, et al.
patients [7,13,15] and with lower recurrence-free survival in breast cancer patients treated with neoadjuvant chemotherapy [16–18]. In fact, King et al.  and Dontchos et al.  reported that greater BPE was strongly predictive of breast cancer odds and was associated with a higher probability of developing breast cancer in women at high risk. On the other side, Bennani Baiti et al.  found that neither BPE nor fibroglandular tissue independently correlated with breast cancer risk in non-high-risk patients at MRI and Van der Velden et al.  showed that BPE in the contralateral breast of patients with invasive unilateral breast cancer was significantly associated with long-term outcome.
Breast cancer has been classified during last years into several subtypes by using genetic array testing or approximations to this method using immunohistochemistry [20,21] and guidelines have been established for evaluating estrogen and progesterone receptor expres-sion  and for detecting Human Epidermal Growth Factor Receptor 2 (HER2) over-expression . In fact, the receptorial expression pattern, combined with Ki-67 labeling index, allows to identify different breast cancer subtypes, with different risk factors, natural history and re-sponse to therapies [24–33].
Few authors tried to correlate BPE patterns with molecular breast cancer subtypes [18,20]. Ha et al.  reported that patients with high BPE may be at increased risk for breast cancer but not necessarily for molecular subtypes with poor prognosis. Similarly, Wu et al.  found that higher volume of BPE conferred a higher risk for Luminal B can-cers.
However, no general consensus exists in the medical literature in this field.
The aim of our study is to retrospectively evaluate the distribution of MRI BPE among different breast cancer subtypes searching for any significant difference in terms of immunohistochemical and receptorial panels (Estrogen Receptor -ER, Progesterone Receptor - PR, HER2).
2. Materials and methods
Between January 2017 and June 2017 a total of 137 consecutive female patients (mean age 57, range 39–71, 49 premenopausal, 86 postmenopausal) underwent breast MR examination. Indications to MR examination were represented by family history of breast cancer and dense glandular structure (n = 61), suspected breast lesions on mam-mography or ultrasonography (n = 46), and preoperative evaluation in breast cancer (n = 30).