Atypical Ductal Hyperplasia of the Breast on Core Needle Biopsy: Risk of Malignant Upgrade on Surgical Excision

Tiffany Sin Hui Bong; Jun Kiat Thaddaeus Tan; Juliana Teng Swan Ho; Puay Hoon Tan; Wing Sze Lau; Tuan Meng Tan; Jill Su Lin Wong; Veronique Kiak Mien Tan; Benita Kiat Tee Tan; Preetha Madhukumar; Wei Sean Yong; Sue Zann Lim; Chow Yin Wong; Kong Wee Ong; Yirong Sim

doi:10.4048/jbc.2022.25.e7

Atypical Ductal Hyperplasia of the Breast on Core Needle Biopsy: Risk of Malignant Upgrade on Surgical Excision

J Breast Cancer. 2022 Feb;25(1):37-48. doi: 10.4048/jbc.2022.25.e7.

Authors

Tiffany Sin Hui Bong¹, Jun Kiat Thaddaeus Tan¹, Juliana Teng Swan Ho², Puay Hoon Tan³, Wing Sze Lau⁴, Tuan Meng Tan⁵, Jill Su Lin Wong², Veronique Kiak Mien Tan^{1

6

7}, Benita Kiat Tee Tan^{1

6

7

8}, Preetha Madhukumar^{1

6

7}, Wei Sean Yong^{1

6

7}, Sue Zann Lim^{1

6

7}, Chow Yin Wong^{6

7}, Kong Wee Ong^{1

6

7}, Yirong Sim^{1

6

9}

Affiliations

¹ Department of Breast Surgery, Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore.
² Division of Oncologic Imaging, National Cancer Centre Singapore, Singapore.
³ Division of Pathology, Singapore General Hospital, Singapore.
⁴ Department of Clinical Laboratory, Gleneagles Hospital Hong Kong, Hong Kong.
⁵ Department of Statistics and Applied Probability, National University of Singapore, Singapore.
⁶ Department of Breast Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore.
⁷ SingHealth Duke-NUS Breast Centre, Singapore.
⁸ Department of General Surgery, Sengkang General Hospital, Singapore.
⁹ SingHealth Duke-NUS Breast Centre, Singapore. sim.yirong@singhealth.com.sg.

Abstract

Purpose: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making.

Methods: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010-2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination.

Results: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005-0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21-25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831-1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram.

Conclusion: Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74-0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Keywords: Breast; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Nomograms; Prognosis.