DOI: 10.25934/pr00009939
title: Organ specific tumor dynamic predict survival in patients with metastatic breast cancer

description: Background
Breast cancer, a type of cancer that starts in the breast cells, is one of the most common cancers in women, which has a 5-year survival rate of 99% if the patient has cancer only in the breasts. However, the rate will down to 26% for those metastasis, and ~ 75% of deaths in breast cancer were associated with metastasis (when cancer cells spread from where they first formed to other parts of the body). In this study, we will focus on metastatic breast cancer. We initiate this study because:
1) Different metastatic patterns (e.g., patient with metastasis in liver and lymph node vs only in lymph node) may be associated with different survival outcomes. Understanding the association between the patterns and prognosis may help to allocate the patient to receive more proper treatment and thus improve survival outcomes.

2) The current tumor response, how the tumor reacts or changes when it's treated, is defined by the how much the tumor has shrunk by measuring its longest parts (tumor size reduction of the sum of the longest diameter). Thus, the location that the cancer has spread to from its original location, called the metastatic site location, is often overlooked in patients with metastasis. However, the literature has demonstrated that the tumor dynamics (changes/behavior of tumors over time such as the tumor growth rate (KG) and Early Tumor Shrinkage (ETS)) for different organs did not contribute equally to survival outcomes. We want to investigate the effect of organ-specific tumor dynamics, how tumors behave and grow differently depending on the organ they develop, on survival outcomes. 

3) Different treatment strategies may result in different organ-specific responses. Thus, we will include the studies investigating the treatment effect of the following treatments used in breast cancer patients:

hormonal therapy- uses medications to block or interfere with the hormones 

chemotherapy- uses drugs to kill or slow the growth of  cancer cells

anti-vascular endothelial growth factor (VEGF)- blocks the growth of new blood vessels that tumors need to grow/spread.

anti-human epidermal growth factor receptor 2 (HER2)- targets, blocks the activity of the HER2 protein, which is overexpressed in some cancer cells, particularly in breast cancer, helping to slow down/stop cancer growth.

immune checkpoint inhibitors, programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) inhibitors- used to help the immune system recognize and attack cancer cells by blocking proteins that prevent immune cells from recognizing and targeting cancer cells.

antibody-drug conjugate (ADC)- combines a cancer-targeting antibody with a chemotherapy drug to deliver the drug directly to cancer cells

Method
We will study how tumor size changes over time for each affected area, along with any side effects, lab test results, and basic information (age, gender, etc.). A model called a tumor growth inhibition (TGI) model will be used to estimate KG, and the EST will be calculated. Commonly used statistical analysis methods and the R software will be used for data analysis and plotting.

Necessity of the research
Our study may have the following implications:
(1) Understanding the association between the patterns and prognosis and help to choose a better treatment strategy.
(2) Investigating the relationship between different treatment strategies and organ-specific tumor dynamics, and the effect of organ-specific tumor dynamics on survival outcomes. These results may help to improve the clinical trial design.