An Evolving Role of Antitumor Activity of Zoledronic Acid in Breast Cancer View PDF

S Nanditha
Medicine, Rajarajeswari Medical College And Hospital, Bengaluru, Karnataka, India
Polusani Pratham
Medicine, Government Medical College, Nizamabad, Telangana, India
Mullapudi Surendranadh Chowdary
Medicine, GSL Medical College & General Hospital, Rajahmundry, Andhra Pradesh, India
Vineela Kanneboyina
Medicine, Narayana Medical College And Hospital, Nellore, Andhra Pradesh, India

Published on: 2024-12-01

Abstract

Breast cancer patients with bone metastases benefit from bisphosphonates by reducing fracture risks, spinal cord compression, and hypercalcemia caused by bone metastases. Traditionally, zoledronic acid has been administered on a monthly schedule via intravenous injection. It has been demonstrated in preclinical studies that zoledronic acid can inhibit tumor cell invasion, adhesion, and angiogenesis. The anti-tumor effects and bone health benefits of zoledronic acid therapy have been demonstrated in several clinical studies conducted with postmenopausal women during adjuvant breast cancer treatment at various timings and schedules. According to several observations and postmenopausal data, zoledronic acid’s anticancer activity may be affected by the endocrine environment. It appears zoledronic acid may be most effective for improving disease-free survival in women who are postmenopausal or have endocrine therapy-induced menopause in the adjuvant setting. In general, zoledronic acid is most effective when initiated early, concomitantly with adjuvant therapy. Still, zoledronic acid’s relative potency and the most effective schedule of treatment remain unclear. To examine the effectiveness of zoledronic acid therapy in patients with breast cancer, we reviewed existing clinical studies.

Keywords

Zoledronic acid, Advanced breast Cancer, Bone metastases

Introduction

A cancer patient’s bone is the most common site of tumor metastasis, accounting for about 20-25% of all cancers. In addition to cancers of the breast, the lung, the prostate, the kidney, and the thyroid, bone metastases are also common. Reactive bone formation results in some osteoclastic metastases, while others are osteoblastic or mixed [1]. Approximately 2.1 million new cases of breast cancer are diagnosed each year, making it the leading cause of cancer deaths among women. In the United States, one in eight women is at risk of developing breast cancer during their lifetime [2]. It is still challenging to prevent local or distant relapse after surgery and adjuvant treatment, even in patients with no evidence of residual disease. Patients with metastatic breast cancer often experience bone recurrence, with up to 80% developing lesions in the bone. Hematopoietic niches are supported by the bone marrow, which is highly vascularized and contains a number of growth factors, cytokines, and other signaling molecules. In addition to protecting pluripotent hematopoietic stem cells from immune activity and other attacks, this environment can act as an inadvertent sanctuary for cancer cells [3-6]. Consequently, bone microenvironment may act as a shield against chemotherapeutic agents, thereby promoting cancer cell survival and tumor growth.

As of the time of writing, the only bisphosphonate indicated for solid tumors with bone metastases is zoledronic acid. As compared to clodronate, pamidronate, risedronate, alendronic acid, and etidronate, it is about 100 - 1000 times more potent. Inhibiting farnesyl diphosphate synthase, a mevalonate pathway enzyme, causes zoledronic acid to reduce post-translational prenylation of proteins, disrupting essential metabolic pathways of cancer cells [7]. In addition to its direct antitumor effects, zoledronic acid may modulate the immune system indirectly as well. This compound contains a phosphate residue, which is recognized by gamma delta T cells in the mediation of immune responses against tumor cells. For the treatment of osteoporosis and bone metastases, zoledronic acid has been administered according to several dosing schedules. Zoledronic acid has been studied in a variety of dose schedules, including conventional doses (4 mg intravenously every 3 to 4 weeks), maintenance doses (4 mg intravenously every 3 to 6 months), and metronomic doses (1 mg intravenously weekly). Dosing schedules may have different anti-tumor effects [8]