A Short Communication on Lung Metastasis in Breast Cancer: Clinical and Experimental Perspectives View PDF

Saipriya Thota
Medicine, Davao Medical School Foundation, Inc., Bajada, Davao City, Philippines
Royyuru Kesavi Seshu Priya
Medicine, Malla Reddy Institute Of Medical Sciences, Hyderabad, Telangana, India
Afla Subhana
Medicine, Travancore Medical College, Kollam, Kerala, India
Sathvika Reddy Mittapally
Medicine, All India Institute Of Medical Sciences, Guwahati, Assam, India

Published on: 2025-01-17

Abstract

Approximately 90% of all breast cancer-related deaths occur due to metastasis, which is the most common type of cancer in women worldwide. The spread of breast cancer is preferential to the lung, brain, bone, and liver, which is known as organ tropism. The lack of early prognostic/predictive methods to determine which organs are most likely to develop metastases has made current treatment methods for metastatic breast cancer ineffective. Most cancer patients die from distant metastases. Based on gene expression profiles, breast cancer can be classified into different subtypes, and different subtypes prefer to metastasize to different organs. Breast tumors that are luminal tend to metastasize to bone, whereas those that are basal-like are more likely to metastasize to the lungs. There is, however, still a need to investigate the mechanisms underlying this organ-specific pattern of metastasis. It is crucial to understand the mechanisms that drive breast cancer metastasis in order to identify novel biomarkers as well as therapeutic targets. 65% of patients who develop lung metastasis die as a result of this disease, which is associated with significant morbidity and mortality. The purpose of this review is to summarize current understanding of breast cancer metastasis to the lung and to discuss potential new treatment approaches for breast cancer metastasis to the lung.

Keywords

Breast cancer, Lung metastasis, Pre-metastatic niche, Exosomes, Tumor secreted factors, Targeted therapies

Introduction

Approximately 785,423 women worldwide died from breast cancer in 2024, making it the most common malignancy in women. Because of lifestyle factors, breast cancer has historically been a higher burden in developed nations. A 'westernized' lifestyle and advances in health infrastructure have resulted in an increase in breast cancer incidence rates in developing nations. Approximately 2 in 10 women in western countries will develop breast cancer during their lifetime, and 1 in 29 will die from it [1]. Approximately 86% of breast cancer deaths are due to metastasis-related complications. Tumor cells are detached from their primary tumor and infiltrated into the blood stream during metastatic process. After arresting capillaries of distant organs, the circulating tumor cells (CTCs) extravasate into the parenchyma of the secondary organ, generating metastatic colonies [2].

Improved survival rates for breast cancer have been achieved by improving early detection and treatment. However, a substantial number of patients will relapse due to organ metastasis, especially those with triple-negative breast cancer (TNBC), which has the worst prognosis. It is possible for breast cancer cells to spread to distant sites, specifically the lungs, liver, bones, and brain [3]. Many patients die as a result of these macro proliferative masses. Recurring breast cancer patients with distant metastases have a survival rate of less than 20% after 5.2 years. It is most common for breast cancer to spread to the lungs, bones, and liver. It is estimated that about 60% of patients with metastatic breast cancer will suffer lung or bone metastases during their lifetime. The lungs are particularly susceptible to metastasizing from basal like breast cancer (BLBC). In these cases, survival is low, with the median survival only 21 months following lung metastasis treatment [4]. The presence of lung metastases was diagnosed in 65 - 75% of patients with metastatic breast cancer who died. Despite the availability of many treatment options for lung metastasis, such as chemotherapy, radiotherapy, and targeted therapy, the survival rate of breast cancer patients with lung metastasis remains low. The development of new therapeutic strategies depends on understanding and elucidating the underlying mechanisms. As a matter of fact, it has been shown that BLBC markers such as epidermal growth factor receptor (EGFR) and FOXC1 are associated with lung metastasis. There are many factors involved in determining which organ or organs are colonized by breast cancer, including the molecular variant. ER, PR, and HER2 receptors as well as the proliferation status determined by Ki67 can be used to subdivide breast cancer into four main clinical subtypes. All subtypes of breast cancer tend to metastasize to the bone, but TNBC has the highest incidence of lung metastases; at 35% compared with 25% for luminal A/B and 30% for HER2+. It is unknown, however, when and by what mechanisms breast cancer molecular subtypes influence lung metastasis. This review summarizes current knowledge about molecular mechanisms driving breast cancer metastasis to the lungs. This article discusses the potential therapeutic approaches to improve the prognosis of breast cancer patients with lung metastases based on the large body of research surrounding this topic [5, 6].