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Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer

Jisun Kim1, Wonshik Han12*, Hyeong-Gon Moon1, Soo Kyung Ahn1, Hee-Chul Shin3, Jee-Man You4, Sae-Won Han5, Seock-Ah Im5, Tae-You Kim5, Hye Ryoung Koo6, Jung Min Chang6, Nariya Cho6, Woo Kyung Moon6 and Dong-Young Noh12

Author Affiliations

1 Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Seoul, 110-744, Korea

2 Cancer Research Institute, Seoul National University, 101 Daehakro, Seoul, 110-744, Korea

3 Department of Surgery, Chung-Ang University College of Medicine, 102 Heuksukro, Seoul, 156-755, Korea

4 Department of Surgery, Sun General Hospital, 29 Mokjungro, Daejeon, 301-725, Korea

5 Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehakro, Seoul, 110-744, Korea

6 Department of Radiology, Seoul National University College of Medicine, 101 Daehakro, Seoul, 110-744, Korea

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Breast Cancer Research 2012, 14:R102  doi:10.1186/bcr3221

See related editorial by Cuzick,

Published: 6 July 2012



Anti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.


We analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.


At a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.


MD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.