br G Dilorenzo et al br Inter rater agreement

G. Dilorenzo, et al.
3.5. Inter-rater agreement
The inter-rater agreement in evaluating BPE patterns on MRI was almost perfect with Cohen’s k = 0.83.
4. Discussion
The introduction of MRI in the field of breast imaging has increased the sensitivity and specificity for detecting breast cancer respectively to 95%–99% and 80%. MRI also provides crucial information concerning the normal breast tissue features, including BPE, defined as the en-hancement of the normal breast tissue after Hexa His tag peptide material injection. BPE can be classified as minimal (< 25% of glandular tissue demon-strating enhancement), mild (25%–50% enhancement), moderate (50%–75% enhancement), or marked (> 75% enhancement). Typically BPE is minimal or mild and shows diffuse, bilateral and symmetric distribution. In a minor percentage of patients, it could be moderate or marked, and could have asymmetric or not diffuse pattern, affecting breast cancer detection [1–4].
BPE is influenced by the anatomy of the breast’s arterial and venous systems, and by endogenous hormones levels during the menstrual cycle; therefore, it is recommended to perform breast MR in the first half of the menstrual cycle, in order to minimize the enhancement of the normal breast tissue. A negative BPE correlation with menopausal status has been reported [1,5–9]. Also hormone therapies can reduce BPE, like selective estrogen receptor modulators (SERMs) or aromatase inhibitors [10]. Verardi et al. [39] reported an association between asymmetric increased breast vascularity and ipsilateral cancer, parti-cularly for invasive cancers of more than 2 cm in diameter or with high pathologic grade. This data suggests to perform any evaluation of BPE on the contralateral breast. In fact, BPE was evaluated in the con-tralateral breast in all patients enrolled in our study.
Several studies investigated the effect of BPE on breast cancer de-tection and its association with different tumor types. Some authors found no correlation between BPE and mammographic density [11–14], but many studies demonstrated that increased BPE at breast MRI was associated with greatly increased risk of breast cancer in high risk patients [7,13,15] and with lower recurrence-free survival in breast cancer patients treated with neoadjuvant chemotherapy [16].
Particularly, Dontchos et al. and King et al. found a positive BPE correlation with breast cancer risk in high risk patients while Bennani-Baiti et al. found no correlation with breast cancer risk in non high risk patients [7,15,19]. Van der Velden et al. also stated that BPE in the contralateral breast of patients with invasive unilateral breast cancer was significantly associated with long-term outcome particularly in case of estrogen receptor-positive, human epidermal growth factor re-ceptor 2 (HER2)-negative breast cancer [17].
In fact, most relevant studies about breast cancer during last dec-ades involve its molecular characterization, using genetic array testing (or approximations to this method with immunohistochemistry) to detect the expression of hormonal and epidermal growth factor 2 re-ceptors in the tumor cells. This data, associated with Ki67 labeling index, allows to classify several cancer subtypes, which differ for etiology, natural history and response to treatment [21].
The 12th, 13th and 14th (2011, 2013 and 2015) St Gallen International Breast Cancer Conference Expert Panel adopted a new approach to the classification of patients for therapeutic purposes based on the recognition of intrinsic biological subtypes within the breast cancer spectrum (Luminal A, Luminal B HER2 -, Luminal B HER 2 +, HER 2 + not Luminal, Triple negative) [36–38]. The aim of our study was to retrospectively evaluate the distribution of MRI BPE among different breast cancer subtypes searching for any sig-nificant difference in terms of immunohistochemical and receptorial panels.  European Journal of Radiology 113 (2019) 148–152