Comparative Study on Bone Mineral Density in Premenopausal Patients with Estrogen Receptor-Positive Breast Cancer in ASTRRA Study: A 5-Year Follow-up Study

Eunju Shin¹Seung Il Kim²Min-ho Park³Hyun-Ah Kim⁴Yongsik Jung⁵Jai Min Ryu⁶Eun Hwa Park⁷Sung Yong Kim⁸Eun-Gyeong Lee⁹Min Hyuk Lee⁸Lee Su Kim¹⁰Seock-Ah Im¹¹Soong June Bae¹²Su Hwan Kang¹³Woo Sung Lim¹⁴Hyun Jo Youn¹⁵Heung Kyu Park¹⁶KYONG HWA Park¹⁷Tae Hyun Kim¹⁸Shin Young Park¹⁹Cheol Wan Lim²⁰Geum Hee Kwak²¹Chanheun Park²²Hyukjai Shin²³Young Bum Yoo²⁴Sun Hee Kang²⁵Bong Kyun Kim²⁶Hee Jeong Kim^1*

• ¹Asan Medical Center, Seoul, Republic of Korea
• ²College of Medicine, Yonsei University, Seoul, Seoul, Republic of Korea
• ³Chonnam National University Medical School, Gwangju, Gwangju, Republic of Korea
• ⁴Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, Republic of Korea
• ⁵Ajou University Hospital, Suwon, Gyeonggi, Republic of Korea
• ⁶Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
• ⁷College of Medicine, Dong-A University, Busan, Busan, Republic of Korea
• ⁸College of Medicine, Soonchunhyang University, Seoul, Republic of Korea
• ⁹National Cancer Center, Goyang-si, Republic of Korea
• ¹⁰Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi, Republic of Korea
• ¹¹Seoul National University Hospital, Seoul, Republic of Korea
• ¹²Gangnam Severance Hospital, Seoul, Seoul, Republic of Korea
• ¹³Yeungnam University Medical Center, Daegu, North Gyeongsang, Republic of Korea
• ¹⁴Ewha Womans Medical Center, Yangcheon-gu, Seoul, Republic of Korea
• ¹⁵College of Medicine, Jeonbuk National University, Jeonju, North Jeolla, Republic of Korea
• ¹⁶Gachon University Gil Hospital, Incheon, Incheon, Republic of Korea
• ¹⁷Korea University Medical Center, Seoul, Republic of Korea
• ¹⁸Inje University Busan Paik Hospital, Busan, Republic of Korea
• ¹⁹Medical School, Inha University, Incheon, Republic of Korea
• ²⁰Soon Chun Hyang University Bucheon Hospital, Bucheon, Gyeonggi, Republic of Korea
• ²¹Inje University Sanggye Paik Hospital, Seoul, Republic of Korea
• ²²Kangbuk Samsung Hospital, Seoul, Republic of Korea
• ²³Myongji Hospital, Seoul, Gyeonggi, Republic of Korea
• ²⁴Konkuk University Medical Center, Seoul, Republic of Korea
• ²⁵Keimyung University, Daegu, Daegu, Republic of Korea
• ²⁶Daejeon St. Mary’s Hospital, Daejeon, Republic of Korea

We compared the impact of tamoxifen alone or with ovarian function suppression (OFS) on bone mineral density (BMD) in premenopausal patients after chemotherapy.Of 1483 premenopausal women enrolled in the ASTRRA study, we included 522 who underwent BMD examinations at diagnosis and 3 and 5 years after diagnosis. All BMD measurements were performed using the same scanner in each center across different time points. Patients were stratified into three groups: within the expected range for age (A, Z-score>-1.0), below the expected range (B, -2.0≤ Z-score ≤-1.0), and low bone mineral density for chronological age (C, Z-score< -2.0) groups. We examined changes in groups from baseline to >3-year and 5-year periods to identify any deterioration in BMD. We conducted a subset analysis using the Asan Medical Center (AMC; n=141) data, focusing on the absolute value of bone density (in g/cm 2 unit).The 522 included patients (median age, 41.1 years) had a higher bone loss incidence in the OFS addition group at baseline (p=0.028). The tamoxifen-only and tamoxifen+OFS groups did not differ significantly in terms of changes in BMD categories from baseline to 3 (p=0.567) or 5 years (p=0.600). The OFS addition group had a significantly increased risk of BMD deterioration when randomized at the first visit (odds ratio=2.970, p=0.008).Within the AMC subset, the OFS addition group exhibited significantly decreased BMD in the spine (p=0.023) and femur (p=0.040) from the baseline to 3-year period. A non-significantly decreased BMD occurred from the baseline to 5 years in the spine and femur.Our findings highlighted the deleterious impact on BMD following OFS addition, compared with tamoxifen only treatment. Early OFS exerted an even more detrimental influence on bone health in premenopausal patients with estrogen receptor-positive breast cancer and recovered ovarian function.