Abstract
Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.
Highlights
Breast cancer is known as the most frequently diagnosed cancer in women
Our study revealed that LCn3PUFA supplementation was able to partially prevent bone marrow damage from adriamycin (doxorubicin) + cyclophosphamide (AC) chemotherapy, as shown by the bone marrow cellularity recovery and reduced marrow adiposity
This study has examined the effects of dietary LCn3PUFA supplementation on long bones of rats subjected to 4 cycles of AC breast cancer chemotherapy
Summary
Breast cancer is known as the most frequently diagnosed cancer in women. In the past decade, treatment for breast cancer has been transformed through changes in biological understanding and clinical presentations of the disease. Since increased risk of bone marrow toxicity has been found to be consistently higher in those receiving alkylating agents or anthracycline-based regimens [1], and anthracycline-based combination chemotherapy continues to be the integral part of breast cancer chemotherapy due to their treatment efficacy, it is important to understand the underlying mechanisms for anthracycline chemotherapy induced-bone marrow/bone defects, and to develop potential strategies for protecting bone marrow and bone during breast cancer chemotherapy. Due to some similarities in bone/bone marrow outcomes and in some cellular processes (including increased osteoclastogenesis, oxidative stress and bone marrow adipogenesis and decreased osteogenesis) between postmenopausal osteoporosis and cancer chemotherapy-induced bone/marrow damages [11,13,14,15], we hypothesized that LCn3PUFA supplementation, which has shown benefits in protecting bone and bone marrow as reported in the above recent clinical and animal studies, may have some efficacy in alleviating bone/bone marrow damage caused by combination breast cancer chemotherapy. The current study addressed whether daily LCn3PUFA supplementation could help to alleviate bone marrow and bone damage during AC combination chemotherapy
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