Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up

Majithia, Neil; Atherton, Philip J.; Lafky, Jacqueline M.; Wagner‐Johnston, Nina D.; Olson, Janet E.; Dakhil, Shaker R.; Perez, Edith A.; Loprinzi, Charles L.; Hines, Stephanie L.

doi:10.1007/s00520-015-2915-2

Cited by 16 publications

(10 citation statements)

References 33 publications

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“…Notably, longer recurrence-free interval (0.75 [0.57–0.99]; P=0.045), as well as bone and non-bone metastasis-free interval were observed when post-menopausal women aged more than 50 years were included (44). In the ABCSG-12 trial, addition of zoledronic acid to adjuvant therapy (tamoxifen or anastrozole) significantly increased DFS at 48 months (HR =0.64, p=0.01) and at 62 months (HR=0.68, p=0.009) (45, 46). Prolonged DFS and improved OS were confirmed after a median follow up of 95 months (46).…”

Section: 0 Breast Cancermentioning

confidence: 99%

Evaluation and management of skeletal disease in cancer care

Kommalapati

Tella

Esquivel

et al. 2017

Critical Reviews in Oncology/Hematology

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Recently, there have been considerable advancements in cancer therapies thereby prolonging the life of cancer survivors. However, these recent advancements present new challenges in the management of bone disease in cancer survivors. Bone acts as a fertile soil for cancer seeding and bone health is often compromised because of increased inflammatory cytokines in cancer, direct cancer metastasis and toxic effects of anti-cancer therapies. This effect is more pronounced in elderly population who already have compromised bone mineral density leading to increased skeletal related events and bone pain. Timely diagnosis and effective interventions are essential for reducing bone-related morbidity in cancer survivors. Also, a complex interdependence exists between cancer related bone disease and tumor growth, creating a vicious circle of extensive bone destruction and cancer progression. Hence, maintenance of bone health and integrity plays a pivotal role in comprehensive cancer care. The bone-targeted treatments have been shown to preserve bone health, and modify the course of the underlying cancer. Management of long-term bone health requires a broad knowledge base that both endocrinologists, oncologists and other care team members should be aware of. The manuscript highlights the skeletal effects of cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy induced bone loss and steps for accurate diagnosis and management of bone disease in cancer survivors by bridging the gaps in the comprehensive cancer care.

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Section: 0 Breast Cancermentioning

confidence: 99%

Evaluation and management of skeletal disease in cancer care

Kommalapati

Tella

Esquivel

et al. 2017

Critical Reviews in Oncology/Hematology

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“…The results from this study are consistent with previously published reports that bone density declines in postmenopausal women who begin AI therapy. 19 , 20 This happens because AI suppresses the anti-absorptive effect of estrogen on osteoclasts. This effect can be overcome by inhibition of osteoclast activity with zoledronic acid.…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

Sun

Wang

Dou

et al. 2016

OTT

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BackgroundThis study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.MethodsOne hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations.ResultsPatients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%).ConclusionAI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.

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“…After 5 years, mean BMD had increased by 11.6% at the lumbar spine, a significant difference (p = 0.01), and by 4.2% at the femoral neck, although this was not significant. A total of 6 fractures were observed after 417 individual assessments [22].…”

Section: Bisphosphonatesmentioning

confidence: 99%

“…Several large trials have investigated the potential of adjuvant zoledronic acid to prevent recurrence of breast cancer. In ABCSG-12 [22,24], adding zoledronic acid (4 mg every 6 months for 3 years) to adjuvant therapy (tamoxifen or anastrozole) significantly prolonged DFS both at 48 months (HR = 0.64, p = 0.01) and at 62 months (HR = 0.68, p = 0.009). The final analysis after a median follow-up of 95 months [24] confirmed the beneficial impact of zoledronic acid on DFS and the improvement in OS.…”

Section: Breast-cancer Adjuvant Therapy With Bisphosphonatesmentioning

confidence: 99%

Osteoporosis management in patients with breast cancer: EMAS position statement

Trémollières

Ceaușu

Depypere³

et al. 2017

Maturitas

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Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is currently a general consensus that a careful baseline evaluation is needed of the risk of fracture in postmenopausal women about to start treatment with AIs but also in all premenopausal women with early disease. Bisphosphonates have been shown in several phase III trials to prevent the bone loss induced by cancer treatment, although no fracture data are available. Even though they do not have regulatory approval for this indication, their use must be discussed with women at high risk of fracture. Accordingly, several guidelines recommend considering treatment in women with a T-score ≤-2 or those with two or more clinical risk factors. Moreover, recent data suggest that bisphosphonates, especially intravenous zoledronic acid, may have an anticancer effect, in that they reduce bone recurrence as well as extra-skeletal metastasis and breast cancer mortality in postmenopausal women. The anti-RANK ligand antibody denosumab is also emerging as a new adjuvant therapeutic option to prevent AI-induced bone loss. It has been shown to extend the time to first fracture in postmenopausal women treated with AIs. Several issues still need to be addressed regarding the use of these different agents in an adjuvant setting. The purpose of this position statement is to review the literature on antifracture therapy and to discuss the current guidelines for the management of osteoporosis in women with early breast cancer.

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Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up

Cited by 16 publications

References 33 publications

Evaluation and management of skeletal disease in cancer care

Evaluation and management of skeletal disease in cancer care

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

Osteoporosis management in patients with breast cancer: EMAS position statement

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