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Osteoporosis, an indicator of significant bone loss, has been consistently reported among older breast cancer survivors. Data are limited on the incidence of osteopenia, an earlier indicator of bone loss, and osteoporosis in younger breast cancer survivors compared with cancer-free women.
Younger breast cancer survivors are at higher risk for osteopenia and osteoporosis compared to cancer-free women. Studies are needed to determine effective approaches to minimize bone loss in this population.
Osteopenia and osteoporosis, both systemic skeletal conditions associated with varying degrees of bone loss, are prevalent among postmenopausal breast cancer survivors, with prior reports of up to 80% experiencing loss in bone density [1]. Untreated bone loss can lead to significant morbidity due to pain and fractures, as well as to death [2]. Osteopenia is diagnosed among individuals with lower-than-average bone density, while osteoporosis is characterized by both low bone density and architectural deterioration of bone tissue [3]. Among breast cancer survivors, cancer-related risk factors for osteopenia and osteoporosis include both treatment and premature menopause [4]. Importantly, the excess risk of osteopenia and osteoporosis among breast cancer survivors, particularly those of a younger age, relative to their cancer-free peers remains unknown.
Few epidemiologic studies have examined osteopenia and osteoporosis in breast cancer survivors relative to cancer-free women within the same cohort [8,9,10]. One prior study reported significantly lower levels of bone mineral density [8], the gold standard for assessing bone loss, and two other previous studies observed an increased risk of osteopenia and osteoporosis [9, 10] compared with cancer-free women. These studies were primarily conducted among older and long-term breast cancer survivors and did not differentiate based on tumor subtypes and detailed treatment regimens. One reason for the paucity of studies among younger breast cancer survivors is likely the challenge of identifying a comparable cancer-free group, because young cancer-free women do not routinely undergo assessment for bone health. Fortunately, we found this not to be the case in women with familial breast cancer risk, and we were therefore able to prospectively examine the risk of osteopenia and osteoporosis in a familial risk cohort known as the Breast and Ovarian Surveillance Service (BOSS) study.
To identify whether bone loss differed by subgroups of breast cancer survivors, we examined the risk of osteopenia and osteoporosis in survivors stratified by age at diagnosis, menopausal status at diagnosis, ER tumor status, and breast cancer treatment relative to cancer-free women. For models that stratified breast cancer survivors by ER status, survivors were restricted to invasive breast cancer because ER status was not routinely measured in women with a stage 0 diagnosis. We were unable to conduct analyses by HER2 status or triple-negative breast cancer, due to small numbers. We additionally conducted analyses by family history of breast cancer (no family history, first-degree relative only, first- and second-degree relatives) and an exploratory analysis by BRCA1/2 carrier status among a subgroup of women with genetic testing.
To our knowledge, this is the first study to prospectively assess risk of osteopenia and osteoporosis in young and recently diagnosed breast cancer survivors compared with their cancer-free peers in a familial high-risk cohort. In this prospective study, the incidence of osteopenia and osteoporosis was almost twofold higher in breast cancer survivors than in cancer-free women over an average of 5.8 years of follow-up. The results were also similar when we excluded women with premature menopause, suggesting an effect of cancer treatment on bone health that is independent of early menopause. Breast cancer survivors who were younger, had ER-positive tumors, received aromatase inhibitors alone, or received combined chemotherapy with aromatase inhibitors or tamoxifen had a higher risk of osteopenia and osteoporosis than cancer-free women. Importantly, this was after accounting for age, menopause, and other risk factors for bone loss.
The most common cause of bone loss in women is menopause and aging. Aging is associated with greater bone resorption and less bone formation, whereas menopause induces accelerated bone loss due to lowering levels of endogenous estrogen [26]. Therefore, a cancer-free comparison of similar age and menopausal status is important when assessing bone loss. Given that we still observed significantly higher bone loss in breast cancer survivors relative to their cancer-free peers after accounting for age and menopause, it is likely that the additional bone loss is due to the effect of treatment on bone formation.
In summary, our results demonstrate that incident osteopenia and osteoporosis are significantly higher in young breast cancer survivors within a few years of diagnosis than in cancer-free women and that risk varies by cancer treatment. These findings provide support for a baseline evaluation of bone density and fracture risk assessment close to breast cancer diagnosis, particularly among young survivors being treated with combined chemotherapy and hormone therapy, so that prevention strategies and appropriate monitoring can be implemented early. Future studies are needed to address the frequency of monitoring in breast cancer survivors by specific age and treatment groups.
The workgroup for Positive Youth Development (+PYD) uses the Strategic Prevention Framework. Our mission and vision is to provide practical insight and guidance to support youth in making choices that lead to alcohol and drug free lives.For more information or to get involved, contact us at: koconnor@oakparktownship.org or 708-383-8005, ext. 125.
This program is geared towards parents and caregivers from birth through 12th grade (even beyond). Join distinguished speakers that inspire, connect and inform with research-based strategies that promote positive youth development. Programs are free and open to the public. Links and details at GlenbardGPS.org.
Working together as a family boosts bonding and increases protective factors. Youth say parents are the number one reason why they choose not to use drugs and alcohol. FACE IT is an early intervention and prevention program for middle and high school students and their caregivers. For more information please contact; koconnor@oakparktownship.org or call 708.383.8005 ext.125.
Yadav, A.; Maertens, L.; Meese, T.; Van Nieuwerburgh, F.; Mysara, M.; Leys, N.; Cuypers, A.; Janssen, P.J. Genetic Responses of Metabolically Active Limnospira indica Strain PCC 8005 Exposed to γ-Radiation during Its Lifecycle. Microorganisms 2021, 9, 1626.
Yadav A, Maertens L, Meese T, Van Nieuwerburgh F, Mysara M, Leys N, Cuypers A, Janssen PJ. Genetic Responses of Metabolically Active Limnospira indica Strain PCC 8005 Exposed to γ-Radiation during Its Lifecycle. Microorganisms. 2021; 9(8):1626.
Yadav, Anu, Laurens Maertens, Tim Meese, Filip Van Nieuwerburgh, Mohamed Mysara, Natalie Leys, Ann Cuypers, and Paul Jaak Janssen. 2021. "Genetic Responses of Metabolically Active Limnospira indica Strain PCC 8005 Exposed to γ-Radiation during Its Lifecycle" Microorganisms 9, no. 8: 1626. 2ff7e9595c
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