Nanomedicine and Nanotherapy: A New Frontier in Breast Cancer Bone Metastasis Diagnosis, Treatment, and Management View PDF

Yedluri Dimplesriramya
Medicine, All India Institute Of Medical Sciences, Raipur, Chhattisgarh, India
^*Rahul Akkapeddi
Medicine, Gandhi Medical College, Secunderabad, Telangana, India
Palle Esha Reddy
Medicine, Kurnool Medical College, Kurnool, Andhra Pradesh, India
Sharon Manoj Oommen
Medicine, Adichunchanagiri Institute Of Medical Sciences, B.G Nagara, Karnataka, India

^*Corresponding Author:

Rahul Akkapeddi
Medicine, Gandhi Medical College, Secunderabad, Telangana, India

Published on: 2025-07-01

Abstract

Breast cancer bone metastases (BCBM) represent a significant clinical challenge due to their complex pathophysiology, resistance to conventional therapies, and the unique tumor microenvironment within the bone. Nanotherapy has emerged as a promising approach to address these challenges by enabling targeted drug delivery, improving therapeutic efficacy, and minimizing systemic toxicity. Advances in nanotechnology have facilitated the development of nanoparticles that can overcome the blood - bone barrier, deliver chemotherapeutic agents, gene therapies, and bone-targeting molecules directly to metastatic lesions, and enhance the precision of treatment through multifunctional platforms like theranostic nanoparticles. Clinical trials using liposomal formulations, bone-targeting nanoparticles, and gene therapy-based carriers have shown promising results in improving patient outcomes while reducing adverse effects. Despite these advancements, challenges such as nanoparticle toxicity, variability in drug distribution, and the high cost of manufacturing remain barriers to widespread clinical adoption. Future prospects include the design of smart, stimuli-responsive nanoparticles, integration with gene-editing tools like CRISPR-Cas9, and the incorporation of theranostic capabilities for real-time treatment monitoring. Personalized nanomedicine, enabled by biomarkers and artificial intelligence (AI), holds the potential to revolutionize the management of BCBM, offering tailored therapies that improve efficacy and minimize side effects. Continued innovation and clinical validation are essential to realize the full potential of nanotherapy in transforming the treatment landscape for BCBM patients.

Keywords

Breast cancer bone metastases, Nanotherapy, Targeted drug delivery, Bone targeted nanoparticles, Gene therapy, Nanotheranostics, Personalized medicine

Introduction

Insights into BC statistics

BC remains a significant global health issue, with rising incidence and mortality rates observed across various regions. BC is the most diagnosed cancer in females globally, with varying incidence rates across regions. Highest rates in Australia/New Zealand, Western Europe, and Northern America; lowest in South-Central Asia and Africa [1]. The global burden of BC has escalated from approximately 875,657 cases in 1990 to over 2.1 million in 2021, with age-standardized incidence rates (ASIR) showing stark regional disparities. High sociodemographic index (SDI) regions report the highest ASIR, while low SDI regions experience the lowest rates [2]. In 2020, BC accounted for 2.3 million new cases and 685,000 deaths, making it the most diagnosed cancer in women [1]. The ASIR in Australia/New Zealand was 95.5 per 100,000, while South-Central Asia reported only 26.2 per 100,000 [3]. Africa shows the highest mortality-to-incidence slope, indicating poorer outcomes [3]. High HDI regions like Western Europe and Northern America have lower mortality rates compared to low HDI regions, where rates are increasing [1]. Globally, BC mortality rates declined from 16.33 in 1980 to 14.54 in 2021. Asia and Africa show rising trends, with Africa experiencing the highest increase. Highincome countries have decreasing rates, while lower-middle-income countries face rising mortality [4].

By 2040, BC cases are projected to rise to nearly 3 million globally, emphasizing the need for targeted interventions [1]. Despite improvements in high SDI regions, the increasing burden in low SDI areas highlights the urgent need for equitable healthcare access and targeted prevention strategies to address these disparities [2, 3]. The projections for BC cases by 2040 indicate a significant increase globally, with estimates suggesting over 3 million new cases annually. This rise is attributed to various factors, including demographic changes, lifestyle shifts, and improved detection methods. An estimated 2,964,197 new BC cases are projected for 2040, marking a 31% increase from 2020 [1]. Other estimates suggest that cases could reach 364,000 in specific regions by 2040 [5]. The overall trend indicates a global rise in BC incidence, particularly in lower-developed countries due to lifestyle changes and fertility patterns [5]. Contributing factors are: (i) Demographic changes: The aging population is a significant factor, with the proportion of cancer cases in individuals over 60 expected to rise from 62% to 76% by 2040 [6], (ii) Lifestyle factors: Adoption of Western lifestyle behaviors, including diet and physical inactivity, contributes to increased cancer risk [1], and lastly (iii) Healthcare access: Disparities in access to early detection and treatment exacerbate mortality rates, especially in socio-economically disadvantaged regions [5]. While the projections highlight a concerning trend in BC incidence, it is essential to consider that advancements in early detection and treatment may mitigate some of the anticipated mortality rates, particularly in highincome countries.
Influencing Factors in BC

BC is influenced by demographic, lifestyle, genetic, environmental, hormonal, and reproductive factors (Table 1). Hormonal factors such as prolonged estrogen exposure, along with genetic mutations in BRCA1/BRCA2, increase susceptibility. Environmental exposures like radiation and lifestyle choices such as obesity or alcohol consumption further elevate risk. Demographic factors, including age, ethnicity, and socioeconomic status, also play a critical role, with disparities in access to care and aggressive subtypes observed in specific populations.

Demographic and lifestyle

Geographic variability significantly influences the demographic and lifestyle factors associated with BC risk, as evidenced by various studies examining the interplay of environmental, socioeconomic, and healthcare access factors across different regions. These studies reveal that the impact of these factors is not uniform, highlighting the need for localized public health strategies. The following sections outline the key demographic and lifestyle influences on BC risk.