Breast Cancer by Age, Prediction of Patient Outcomes

A study performed by Sanford Burnham Prebys researchers discovered that specific genetic abnormalities are linked to treatment-resistant breast cancer in young women. These mutations do not appear to be associated with treatment-resistant breast cancer in older women. The findings, which were published in the journal Science Advances, have the potential to improve precision medicine and provide a completely new approach of diagnosing breast cancer.

“It’s well established that as you get older, you’re more likely to develop cancer. But we’re finding that this may not be true for all cancers depending on a person’s genetic makeup,” says senior author Svasti Haricharan, Ph.D., an assistant professor at Sanford Burnham Prebys. “There may be completely different mechanisms driving cancer in younger and older people, which requires adjusting our view of aging and cancer.”

The study concentrated on ER+/HER2- breast cancer, which is one of the most frequent types of the illness. It is typically treated with hormonal therapy, although these treatments do not work for many people. Approximately 20% of cancers resist treatment from the start, and up to 40% develop resistance over time.

“Understanding how certain forms of breast cancer develop in a way that makes them eventually resist therapy can help us better classify the disease. It may also help clinicians adjust the treatment plans for patients who will likely experience resistance to standard treatments,” says Haricharan. “For scientists like myself, it can help guide research to develop new therapies to overcome these obstacles.”

The study includes a thorough examination of a huge database of breast cancer patients. It discovered that some gene alterations in ER+/HER2- breast cancer patients showed a substantial link with treatment response—and the effects were age-dependent. Only in younger women were several gene alterations connected to treatment-resistant breast cancer.

“This was a strange finding, so much so that we almost didn’t believe it at first,” says Haricharan. “But the same patterns emerged over and over again in database after database.”

The researchers discovered alterations in genes essential in cell replication, the mechanism by which cells grow and divide. These genes are in charge of fixing mistakes when they occur, a process that fails in nearly all malignancies.

Cell cycle dysregulation occurs so early in the development of cancer that we generally don’t consider whether the individual mutations that cause cell cycle dysregulation can affect cancer’s eventual response to treatment or its ability to spread,” says Haricharan.

The research team offers an altogether new paradigm for thinking about and studying all types of cancer by linking the exact sort of cell cycle dysregulation that causes cancer with the fate of the disease many years after diagnosis.

“This is a radical shift in how we look at cancer, which could have implications well beyond breast cancer,” adds Haricharan.

To put this theory to the test, the researchers looked at the impact of cell cycle alterations on patient outcomes in different forms of cancer. Finally, they discovered that the manner of cell cycle dysregulation is significant for cancer in women but not for cancer in males across various cancer types. This shows that the impact of cell-cycle dysregulation may differ depending on gender as well as age.

“These findings emphasize why it is important to study cancer in the context of the life history of the patient,” adds Haricharan. “Too often, cancer research is focused narrowly on cells in a petri dish, forgetting the whole, complex host system in which these cells transform and grow.”

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