1. 骨質疏鬆是否為乳癌發生的危險因子
The Gail riskmodel is a well known tool that estimates the 5-year and lifetime risk of invasive breast cancer for women aged ? 35 years. Factors in the original Gail model include the number of first-degree relatives with breast cancer, current age, age at first menstrual period, number of breast biopsies, and age at first live birth. Recently, some studies have found an association between higher BMD and higher breast cancer risk. In the prospective study of Women’s Health Initiative, multivariate Cox proportional hazards model showed the hazards ratio for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (? 1.67%). These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer. But, data for this analysis comprised those collected from women randomized to placebo in the MORE and CORE trials (n = 2,576), the association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age.

2. 乳癌治療中發生的骨質變化
Aromatase inhibitors of the third generation are now widely established in the treatment of early and metastatic breast cancer. Three compounds (anastrozole , letrozole and exemestane) have proven to suppress plasma and tissue estrogen levels by >98% in vivo. Aromatase activity and CYP19 gene expression have been detected in human culture osteoblasts and vitamin D as well as dexamethasone have been identified as two of the major modulating factors of aromatase transcription by influencing on regulatory regions of the promoters, polymorphisms of CYP19 have been shown to be correlated with estrogen plasma levels and BMD in postmenopausal women. All major phase III trials involving aromatase inhibitors in the adjuvant setting have reported increased fracture rates, there is no hard evidence to suggest major differences between the individual compounds concerning their side-effects on bone. The consequences of AI therapy on bone are in addition modified by a variety of factors like the BMD level prior to therapy, time since menopause, and vitamin d status. Chemotherapy is also associated with bone loss, either through direct detrimental effects on osteocytes, resulting in up 1% annual BMD decrease. Therefore, cancer therapy-induced bone loss (CTIBL) is more rapid and of greater magnitude compared with bone loss during normal aging, increasing the need for dietary and lifestyle modifications, plus pharmacologic intervention in some patients.

3. 雙磷酸鹽在乳癌治療中的抗腫瘤效果
Bisphosphonates (BPs)are antiresorptive agents that inhibit osteoclast function and induce apoptosis. They have an established role in treating postmenopausal osteoporosis. Recent data not only support the efficacy of BP for maintaining BMD and preventing CTIBL and AIBL, but also suggest that they may exert anticancer activity in the adjuvant setting for BC. The bone substudy of the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) evaluated the efficacy of BP (4mg IV every 6 months for preventing CTIBL because of endocrine therapy. 5-year LS BMD was significantly increased versus baseline BMD in patients who had received 3 years of BP. The ABCSG-12 trial, adding twice-yearly BP to adjuvant endocrine therapy significantly reduced the relative risk of DFS events by 36% (log-rank p = .01) and recurrence-free survival (RFS)events by 35% (log-rank p = .01) in the overall trial population. The Z-FAST, ZO-FAST, and E-ZO-FAST trials are evaluating the activity of BP (4mg IV qmo) for preventing AIBL and disease progression in postmenopausal women with early stage, early results are consistent with the DFS benefits observed with BP in ABCSG-12.
4. 乳癌併發骨轉移的治療趨勢