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Risk Factors of Breast Intraductal Lesions in Patients Without Pathological Nipple Discharge

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Risk Factors of Breast Intraductal Lesions in Patients Without Pathological Nipple Discharge MOLECULAR AND CLINICAL ONCOLOGY 13: 38, 2020 Risk factors of breast intraductal lesions in patients without pathological nipple discharge LEIHUA SHEN1*, YUQIN YE2*, XIN LIU3, WEIMIN LI4, JINGJING WEI5, ZIRUI KE6, SHAOJUAN YANG7 and ZHAOYING YANG8 1Department of General Surgery, Xi'an Central Hospital, Xi'an, Shaanxi 710004; 2Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, Jilin 130021; 3Department of Science and Education, Shenzhen Center for Chronic Disease Control, Shenzhen, Guangdong 518000; 4Department of Emergency Center, The First Hospital of Yulin, Yulin, Shaanxi 719000; 5Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052; 6Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, Hubei 430070; Departments of 7Pathology and 8Breast Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China Received May 2, 2019; Accepted May 8, 2020 DOI: 10.3892/mco.2020.2108 Abstract. The majority of breast cancer arises from the ductal were statistically significant. Five factors were identified to be epithelium. It is crucial in the diagnosis and treatment of breast associated risk factors in patients without PND through the cancer by detecting intraductal lesions at an early stage. The multivariate logistic regression analysis: Age between 35 and typical clinical characteristic of intraductal lesions is patho‑ 49 years and age ≥50 years [odds ratio (OR)=4.749, 95% logical nipple discharge (PND), although many patients with confidence interval (CI)=2.371‑9.513, P<0.001; OR=2.587, intraductal lesions do not exhibit PND. It is a serious chal‑ 95% CI=2.587‑14.891, P<0.001; respectively], non‑menstrual lenge for clinicians to detect patients with intraductal lesions breast pain (OR=1.922, 95% CI=1.037‑3.564, P=0.038), breast without PND at an early stage. The aim of the present study duct dilatation as seen using ultrasonography (OR=9.455, 95% was to investigate the risk factors associated with intraductal CI=3.194‑27.987, P<0.001), lesion distance from nipple ≤2 cm lesions in patients without PND. This retrospective data‑ (OR=2.747, 95% CI=1.668‑4.526, P<0.001) and lesion size base review, conducted between April 2016 and April 2017, ≤1 cm (OR=1.903, 95% CI=1.155‑3.136, P=0.012). In conclu‑ included 370 lesions from 255 patients with intraductal lesions sion, for patients without PND but with risk factors, such as the (intraductal papilloma, atypical intraductal hyperplasia, patient being >35 years, with non‑menstrual breast pain, breast intraductal carcinoma in situ) and non‑intraductal lesions duct ectasia, lesion distance from nipple ≤2 cm and lesion size (fibroadenoma, adenosis, cysts, lobular carcinomain situ), diag‑ ≤1 cm as seen using ultrasonography, clinicians should be nosed through surgical pathology. The patients were divided highly concerned about the possibility of intraductal lesions, in into two groups based on pathological diagnosis and clinical order to prevent misdiagnosis and reduce the misdiagnosis rate. parameters were evaluated using univariate and multivariate analyses. Univariate analysis revealed that 9 of 14 factors Introduction Intraductal lesions of the breast, include usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), benign intraductal papil‑ Correspondence to: Dr Zhaoying Yang, Department of Breast Surgery, China‑Japan Union Hospital of Jilin University, 126 Xiantai loma (IDP) with or without atypia, and malignant papillary Street, Changchun, Jilin 130033, P.R. China carcinoma (1). Intraductal lesions are often associated with E‑mail: [email protected] pathological nipple discharge (PND), with papilloma being the most common cause (40‑70%), followed by adenomatous Dr Shaojuan Yang, Department of Pathology, China‑Japan Union or papillary epithelial proliferation (14%) (2,3). One to 23% Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, P.R. China of women with PND are diagnosed with invasive breast E‑mail: [email protected] cancer or ductal carcinoma in situ worldwide (4‑6). However, intraductal lesions may be asymptomatic and can be detected *Contributed equally through routine mammography screening. Sometimes they can be found due to other symptoms such as palpable lump(s), Key words: atypical ductal hyperplasia, ductal carcinoma in situ, or associated micro‑calcification (7). intraductal papilloma, pathological nipple discharge Fiber‑optic ductoscopy is important for the diagnosis of patients with PND, and it is now becoming indispens‑ able (8,9). Women without PND are usually diagnosed through 2 SHEN et al: RISK FACTORS OF BREAST INTRADUCTAL LESIONS IN PATIENTS ultrasound‑guided core needle biopsy (CNB) (7,10). However, it Table I. Summary of postoperative histopathology findings. has been reported that physicians fail to obtain the appropriate specimens from atypical or malignant lesions through CNB, Group No. due to histological heterogeneity. It has been demonstrated that CNB is not concordant with surgical excision due to high rates Study of upgrading of precursor lesions into carcinoma (7,10‑16). For Papilloma 111 this reason, numerous authors have advocated surgical exci‑ ADH 29 sion of intraductal lesions, such as benign papilloma (with or DCIS 16 without atypia), but others conclude that CNB would remove Overall 156 all lesions (17,18). Increasingly, the focus of studies has been Control on patients with intraductal lesions without nipple discharge Fibroadenoma 101 than with nipple discharge. However, in none of those studies Cysts 32 have researchers drawn attention to the importance of PND. Fibroadenoma and cysts 6 There is no consensus on whether such patients should undergo routine ductoscopy examination. Recent research has Adenosis and and cysts 38 suggested that precursor lesions of cancer include IDPs and Adenosis 37 ADH (10,19). Therefore, it is important to identify intraductal Overall 214 lesions in women without PND at an early stage. The objective of the present study was to retrospectively ADH, atypical ductal hyperplasia; DCIS, ductal carcinoma in situ. survey potential risk factors associated with intraductal lesions (IDPs, ADH and DCIS) in patients without PND and to provide recommendations for clinicians. the patient; project approval no. 201620218). Even though Materials and methods this was a retrospective study, the hospital Ethics Committee evaluated it carefully and suggested it could waive the Study design and patients' information. The histopathology informed consent (including the 12‑year‑old patient's guard‑ and imaging databases were searched for patients who had been ians), based on our institutional policy of strict maintenance diagnosed with non‑ or intraductal lesions after post‑operative of anonymity. histopathological examination in the 13 month‑period from April 2016 to April 2017 at the Department of Breast Ultrasonography and pathology assessment. All patients Surgery within China‑Japan Union hospital of Jilin University were evaluated using a Philips IU22A Ultrasound Imaging (Jilin, China). The patients presented in outpatient because of system (line probe, probe frequency 9‑15 MHZ) and all ultra‑ routine physical examination or breast palpable lump(s). The sonography examinations were performed by two physicians age range of the patients was 12‑77 years of age, with a median with 5 years of experience in US diagnosis. Each surgically age of 40 years. resected specimen was fixed in formalin and embedded in Lesions with mastitis and invasive carcinoma as indicated paraffin for histological analysis, which was performed through post‑operative histopathological analysis and by three pathologists specialized in breast diagnosis. The patients with PND were excluded. Patients were divided pathologists were blinded to the US reports. Diagnosis was into the following study groups: Intraductal lesions (IDP, made based on the 2012 WHO classification of tumors of the ADH and DCIS) and control group: Non‑intraductal lesions breast (22). (fibroadenoma, adenosis, cysts and lobular carcinoma in situ). In this study, intraductal papilloma included both central Statistical analysis. Statistical analysis was performed using papilloma and peripheral papilloma. Intraductal papilloma with IBM SPSS Statistics for Windows (version 20.0; IBM Corp., an atypical lesion was defined as ADH. DCIS was categorized Armonk). First, comparison of categorical data was conducted as pure DCIS and intraductal papilloma with DCIS. As LCIS using the χ2 test. Then, a multivariate logistic regression arises from the breast lobular epithelium of the breast rather analysis was used to determine risk factors that may be than the breast ductal epithelium, so LCIS was placed under associated with intraductal lesions without PND. P<0.05 was non‑intraductal lesions in our study (20,21). Once eligibility considered statistically significant. was established based on histopathological diagnosis, we extracted data of clinical variables, such as patient age, course Results of disease (year), menopausal status, age at menarche, number of pregnancies and abortions, non‑menstrual breast pain; and Postoperative histopathology findings. A total of 370 lesions imaging features, such as tumor size, number, margin and in 255 patients without PND, and with a postoperative histo‑ shape of masses, distance from nipple, masses with or without pathology diagnosis of intraductal lesions (IDP or IDPs,
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