2.1 Clinical data
This single-center retrospective study enrolled 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018. Since the data were obtained from a picture archiving and communication system, patients' informed consent was not required for this study. The inclusion criteria were: (1) modified radical mastectomy or breast-conserving surgery + axillary lymph node dissection; (2) diagnosis of invasive breast cancer confirmed by routine histopathological and immunohistochemical examinations; (3) no previous history of breast tumors or primary tumors in other locations; and (4) lymphovascular tumor emboli detected by pathologists using immunohistochemistry. Patients were excluded if they had obscured lesions revealed by digital mammograms, were breastfeeding, had underwent lumbar puncture or radiotherapy prior to diagnosis, and had incomplete clinical data.
Mammographic lesions were confirmed either by core needle biopsies or by surgical pathology. All the patients underwent digital mammography preoperatively. All of them were female and aged between 26 and 77 with a median age of 45. They were assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80).
2.2 Digital mammography
GE (Senographe DS) and IMS (GIOTTO IMAGE) systems were used. Four standard body positions were imaged under automatic exposure conditions, and they were the right craniocaudal (RCC) view, left craniocaudal (LCC) view, right mediolateral oblique (RMLO) view and left mediolateral oblique (LMLO) view. When lesions were found in the axillary tail of Spence or near the cleavage, amplified imaging in these locations was done to reveal the lesions fully. The flat-panel detector of internal and external obliques was parallel to the pectoralis major muscle. According to the patients’ body shape, the projecting angle ranged from 40° to 65° and was usually 60°. The glands were fully unfolded, and the skin folds below the breasts and upper abdomen were within the mammographic field.
2.3 Image analysis
The imaging characteristics of breast cancer lesions were described according to the 5th edition of ACR BI-RADS® Atlas published in 2013[13]. The lesions were classified into four types: mass, calcification, architectural distortion, and asymmetry. There could be one or more masses. The masses could be round, lobulated, and irregular. Clear and sharp edges meant well circumscribed margins, clear and sharp edges obscured by glands meant obscured margins, while obscured and spiculated edges meant indistinct margins. Amorphous and fine polymorphic calcifications were included, while typically benign calcifications were excluded. Architectural distortion referred to abnormal deformation of breasts without any mass clearly revealed by imaging. History of trauma and surgery must be ruled out under this circumstance. Focal asymmetry was seen in two images, but lacks the outward border or a mass. There were only few cases of architectural distortion and focal asymmetry (both n < 5). Those cases were excluded to avoid inaccurate statistical results. And the lesion type was classified as mass and calcification only.
Associated features included nipple discharge, interstitial edema, blurring of subcutaneous fat layer, skin thickening, and axillary adenopathy (lymph nodes measuring > 1 cm in the long axis diameter with absence of hilus. If enlarged lymph nodes are new, they need to be clinically combined and further examined). Due to its absence in the LVI negative group (n = 0), nipple discharge was not included as a variable. Thickening of the skin means that the affected breast has localized or diffuse thickening of the skin greater than 2mm in thickness. Interstitial edema and subcutaneous fat layer blurring are caused by the filling and dilation of lymphatic vessels and blood vessels in the breast, while the performance of the whole breast including subcutaneous fat layer is blurring, and multiple cord shadows are seen
2.4 Pathology
Surgically resected breast cancer specimens were fixed in 10% formaldehyde for 24 h, then were dehydrated and embedded in paraffin wax. Sections were prepared. Standard HE stain and streptavidin-peroxidase-biotin (SP) immunohistochemical method were performed. DAB detection systems were used. A score of 3 and more indicated Her-2 overexpression. Positive FISH result of Her-2 gene amplification also indicated overexpression when the score was 2 and more. Ki67 proliferative index (PI) of < 10% indicated low expression level, while that of > 30% indicated high expression level. Ki67 PI of 10% to 30% indicated intermediate expression level[14].
The gold standard of this study was that LVI was defined as the intravenous tumor emboli and lymphatic tumor emboli detected by immunohistochemistry. These two kinds of tumor emboli were clinically referred to as intralymphovascular tumor emboli due to the difficulty of distinguishing them with pathological sections. The specimens were read by a senior pathologist who had been working on breast cancer for 21 years.
2.5 Statistical analysis
The data were analyzed using SPSS Version 19.0. The quantitative data were expressed as means ± SDs. The independent t-test was done for intergroup comparisons. The count data were expressed as frequencies or rates, and the χ2 test or Fisher's method was performed. P < 0.05 indicated statistically significant difference. The count data whose values were 0 were excluded from statistical analysis and listed only in table(s).