Treatment options for older women with breast cancer are often limited due to co-morbidities as well as the tolerability of chemotherapies, often the only therapeutic option for advanced stage metastatic breast cancers. The clinical manifestation of metastasis in a vital organ is the final stage of breast cancer progression and the main culprit of breast cancer related mortality. Thus, there is a pressing need to better understand fundamental mechanisms that enable breast cancer cells to thrive in distal organs. As an organism ages cells throughout the body lose their ability to function or do so abnormally; byproducts and waste molecules build up in circulation and within tissues, and connective tissues become stiffer restricting blood flow and oxygen, collectively leading to damage to DNA, proteins, and lipids. The interaction of disseminated cancer cells with the secondary organ is essential for metastases to thrive and largely dependent on the biology of the specific organs. Despite this, research to date has largely neglected the role of aging in breast cancer as well as breast cancer metastasis, and no therapeutic targets have been identified specifically to aid in the treatment of older breast cancer patients. Thus, there is a pressing need to understand how the age of the patient affects tumorigenesis and metastasis with the goal of developing better treatment options for older women, a particularly vulnerable population. Motivated to bridge this gap in knowledge we took a similar approach to what has been used to define traits that empower metastasis in young hosts to evaluate if there are age-specific traits that enable breast cancer metastasis. Our preliminary data showed that the age of the host significantly affects the traits that enable metastatic colonization and revealed mitochondrial metabolism as a key trait in breast cancer cells extracted from metastases specifically in old hosts. Here, we will test if increased mitochondrial fitness is an essential feature for breast cancer metastasis in old hosts and define the mechanism by which the aging process results in this adaptation. Successful completion of these studies will unveil for the first time an adaptation of age- induced breast cancer metastasis, thus offering a therapeutic target with less toxicity than chemotherapies which in turn has the potential to increase the proportion of older women being able to receive active treatment and improve their quality of life.

While we have significantly advanced the therapeutic options for breast cancer over the past decades, older women are still often making the difficult decision of withstanding the harsh side effects of chemotherapies and consequent severe reduction in quality of life, or not undergo treatment and have their lifespans cut short. Here, we aim to change this paradigm by defining how breast cancer metastasis interact and adapt to the old host tissue environment. Our overarching goal is to unveil novel therapeutic targets that can be effectively used to treat late-stage metastatic breast cancer in older women and thereby significantly impact their prognosis as well as quality of life.