Reference
Chang L, Weiner LS, Hartman SJ, Horvath S, Jeste D, Mischel PS, Kado DM. Breast cancer treatment and its effects on aging. J Geriatr Oncol. 2019 Mar;10(2):346-355. doi: 10.1016/j.jgo.2018.07.010. Epub 2018 Aug 2. PMID: 30078714; PMCID: PMC7062379.
At a glance
This article is a scientific literature review of the emerging evidence of a relationship between breast cancer treatments and conditions related to aging. Early diagnosis, radiotherapy, cytotoxic chemotherapies and targeted molecular therapies have greatly extended the lives of breast cancer patients. Nonetheless, recent evidence suggests that cancer treatments have long-term health effects on survivors, probably due to their action on non-cancer cells.
This review is divided into two parts and outlines both clinical and molecular evidence of the correlation between cancer treatments and an accelerated aging phenotype.
Background
Breast cancer is the most common cancer in women worldwide. However, thanks to early diagnosis techniques and advances in therapy, breast cancer patients are surviving much longer (the 5-year survival rate has risen from 75% in 1976 to 91% in 2017). That said, an increase in life expectancy might also mean a greater risk of manifesting features of accelerated aging, with long-term effects on patient health. This is presumably due to the effects of adjuvant therapies and cancer treatments on non-cancerous cells.
Main findings
As for the clinical evidence, the aspects of patient health that appear most affected by cancer treatment are:
• Accelerated reproductive aging. Women who undergo breast cancer treatment, even at a young age, may experience irreversible amenorrhea, infertility and premature menopause. This may lead to serious consequences on their overall health. In fact, one study suggests that a longer reproductive capacity is associated with greater longevity.
• Impaired cardiopulmonary health. Some studies suggest that patients undergoing breast cancer treatments may age more quickly from a cardiorespiratory point of view. This may be due to the toxic effect that adjuvant chemotherapies have on the non-cancer cells of the cardiovascular system. Moreover, by decreasing bone density, the use of adjuvant therapy with specific drugs called aromatase inhibitors may increase the risk of fractures and osteoporosis. Chemotherapy can also cause neuropathic pain, which can be very debilitating, especially so in older patients.
• Cognitive decline. This is one of the most common symptoms in breast cancer patients; impairment of cognitive functions may last for up to 20 years following treatment. Since cognitive decline is linked to aging even in people who have not experienced breast cancer, several studies show conflicting results on the relationship between treatments, aging, and cognitive decline. In fact, cognitive decline in breast cancer patients does not follow a uniform course but rather results from a complex interaction of age, the presence of other diseases, chemotherapy treatments, and the cancer itself.
This evidence overall shows that breast cancer treatment is associated with transient or permanent physical dysfunction and an accelerated aging phenotype.
As for the molecular mechanisms that play a key role in aging, and are also involved in cancer progression, or in cancer treatments, the following were considered:
• Telomere attrition. This is one of the hallmarks of cellular aging. In patients with breast cancer, the therapies affect the telomere length, contributing to a faster aging process;
• Cellular energetics. Several studies have highlighted the link between cellular aging and dysfunctions in the mitochondria and in the metabolic signaling pathways of cells. Similarly, mitochondrial metabolism appears to play a key role in cancer progression;
• Genome instability. This is a hallmark of cancer as well as of aging. Many chemotherapy treatments contribute to genome instability, as they induce DNA damage in cancer cells;
• Epigenetic alterations. These may contribute to cellular aging and may be greater in patients who have had breast cancer;
• Cellular senescence. The internal signaling pathway that induces cellular senescence, normally activated when there is DNA damage, is also a key pathway in cancer progression. In fact, in cancer cells this pathway is deregulated. Some chemotherapy treatments, actually, are directed precisely toward this pathway. That said, these treatments may also affect normal cells and, though the possible side effects remain unclear, they may likely speed up the entire aging process.
Study limitations
In this literature review, the main limitations lie in the fact that the long-term effects of breast cancer treatments have only been studied for a short amount of time. It is, therefore, difficult to establish precise causal relationships and to identify the exact molecular mechanisms that correlate cancer, cancer treatments, and accelerated aging.
Future outlook
By carrying out further research in this area, it may be possible to improve treatment protocols for patients with breast cancer, in order to mitigate the effects of cancer treatments on aging.
Photo by Sam Moqadam on Unsplash
