Introduction: Postmenopausal with breast cancer have an increased risk of osteoporosis and bone fracture. However, most studies assessing this risk have involved Caucasian women. Thus, little is known regarding the risk of fracture in other ethnic groups. The present study was designed to investigate the risk of bone fracture in Asian women, for whom the risk of breast cancer peaks much earlier (age 40-50 years) than in Caucasian women (age 60-70 years).
Methods: The investigators used Taiwan’s National Health Insurance claims data from 2000 to 2003 and identified 21,952 women with newly diagnosed breast cancer age ≥20 years with no other forms of cancer and no history of hip, distal forearm, or vertebral fracture. A group of 87,808 women without cancer were used as a comparison group. Both groups were followed until the end of 2009.
Results: In the breast cancer cohort, the number of incident cases of fracture per year increased from 89 in 2000 to 319 in 2009.
The breast cancer cohort had a higher risk of osteoporosis-related fractures than the comparison cohort (46.72 vs 42.52 per 10,000 person-years). The adjusted hazard ratio (aHR) for all fractures in the breast cancer cohort was 1.16 compared with the comparison group (P<0.001). When the investigator assessed the aHR by fracture subtype, the breast cancer cohort showed a significantly increased risk for hip (1.18; P<0.05) and vertebral fractures (1.24; P<0.05), but not for fractures of the distal forearm. In addition, the aHRs were significantly increased in the breast cancer group for both traumatic fractures (1.12; P<0.05) and nontraumatic fractures (1.29; P<0.01).
When assessed by age, the aHR for both traumatic and nontraumatic fractures was significantly increased among women with breast cancer <50 years of age for (1.35 and 1.72, respectively; P<0.01 for both comparisons).
Conclusion: Asian women with breast cancer who are younger than 50 years of age are at increased risk for osteoporosis-related fractures and should undergo prophylactic treatment to counteract this elevated risk, the investigators concluded.
Tsa CH, Muo CH, Tzeng HE, Tang CH, Hsu HC, Sung FC. Fracture in Asian women with breast cancer occurs at younger age. PLoS One. 2013;8(9):e75109.
Commentary by Azeez Farooki MD
Dr. Azeez Farooki is an academic endocrinologist practicing in New York City. His expertise includes general endocrinology with a sub-focus in osteoporosis / metabolic bone diseases.
This large study examined the national health insurance registry of Taiwan. Patients were tracked over a maximum of 9 years. They were especially interested in younger patients since breast cancer is diagnosed at an earlier age in Asian women (peaking between 40-50 years). Even in younger women (below age 50) with breast cancer they found a relative increase in fracture risk.
As the authors point out, premenopausal breast cancer patients often (if estrogen receptor positive) receive therapies that cause a treatment induced suppression of ovarian function. Thus, if this was the case, one would expect accelerated bone loss and increased fracture risk. Conversely, if ovarian function and menstrual cycles returned (after withdrawal of gonadotropin-releasing hormone agonist [GnRH agonist] therapy, for example), it is possible that fracture risk would decrease towards baseline. This issue—the return of ovarian function—is not able to be addressed by this study; it is relevant to younger patients who are much more likely to have ovarian function return.
Although in the less than 50-year cohort, there was an increased relative risk of fracture compared to the control cohort of women without breast cancer, one wonders, whether the absolute fracture risk is high enough to warrant treatment as the authors suggest. Another common clinical scenario in young women is a treatment (often chemotherapy or surgical) induced menopause followed by tamoxifen initiation. In this "young" postmenopausal setting, tamoxifen, a selective estrogen receptor modulator (SERM), is an excellent method to protect bone health, usually without the need for the more potent antiresorptives (bisphosphonate or denosumab), since age is an independent risk factor for fracture.
In the setting of aromatase inhibitor use in postmenopausal breast cancer patients, antiresorptive treatment is often initiated despite a relatively low absolute risk of fracture (as calculated by FRAX, which does not include aromatase inhibitor therapy, premature menopause, etcetera as risk factors). The main rationale here is to prevent rapid bone loss caused by aromatase inhibitors and to preserve skeletal health for later in life when fracture risk increases. FRAX takes into account ethnicity; the risk of fractures is lower (holding all other variables such as bone mineral density constant) in Asian Americans compared to Caucasian Americans. Furthermore, it is interesting to note that both pre and postmenopausal Chinese American women have been shown to possess some bone micro-architectural advantages compared to Caucasian American women.1
1. Walker WD, Liu XS, Zhou B, Agarwal S, Liu G, McMahon DJ, et al. Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese-American and white women. JBMR. 2013;28(6):1309-1318.