Breast cancer has different genetic factors in young women

Breast cancer in young women is genetically different from that in older women, according to database analysis conducted by researchers at Sanford Burnham Prebys. Breast cancer in men, their work suggests, may also be genetically distinctive.

Cell cycle dysregulation, a prerequisite for cancer formation, may underpin these disparities, the researchers report. They describe it as a distinct event that determines subtype, metastatic potential, and response to treatment.

This is a sea change in how we look at cancer that could have implications far beyond breast cancer, said senior author Svasti Haricharan, Ph.D.

The results, published in the journalThe progress of scienceit could help improve precision medicine and suggest an entirely new way of classifying breast cancer, they said.

The rate of breast cancer is on the rise among younger women. About a decade ago, the disease rate was between 4% and 6% in this subgroup. Now, about 9% of all new cases are found in women under the age of 45. It is the most common cancer among women aged 15 to 39, and it is estimated that more than 12,000 young women are diagnosed with the disease each year. Younger women are 39% more likely to die of breast cancer than older women.

Most of this increase is due to an increase in the prevalence of regional or distant breast cancer, stages II to IV. A significant number of these patients carry germ cell cancer predisposition mutations, but this does not explain the total disparity.

Breast cancer prevalence by stage is very different between AYAs [adolescent and young women] women younger than 40 and older women, said Rebecca H. Johnson, MD, in a recent ASCO Post. In young AYA women, two-thirds are diagnosed with regional or distant disease, including stage II, III, or IV, while in older women, approximately one-third are diagnosed with stage II, III, or IV disease.

The study analyzed a metadata set composed of six independent studies of patients with breast cancer. It revealed that in patients with ER+/HER2- breast cancer, certain gene mutations had a strong correlation with treatment response, and the effects depended on age. Some genetic mutations have only been linked to treatment-resistant breast cancer in younger women.

This was such a strange finding that we almost didn’t believe it at first, Haricharan said. But the same patterns have surfaced over and over again in one database after another.

The mutations the researchers identified were in genes involved in cell replication. These genes are responsible for repairing errors when they occur, a process that goes wrong in virtually all cancers.

They found itATM the mutation is linked to primary estrogen receptor (ER)+/human epidermal growth factor (HER)2- cancer in older women. Conversely, CHK2 dysregulation induces the formation of metastatic, treatment-resistant, premenopausal ER+/HER2- breast cancer.

The researchers also investigated the effect of cell cycle mutations on patient outcomes in other cancer types. They found that in many types of cancer, the mode of cell cycle dysregulation is significant for cancer in women, but less so for cancer in men. This suggests that the influence of cell cycle dysregulation could be both gender and age dependent.

These findings underscore why it’s important to study cancer in the context of a patient’s life history, Haricharan said. Too often, cancer research focuses narrowly on the cells in a petri dish, forgetting the whole complex host system in which these cells transform and grow.

It is common knowledge that as you get older, you are more likely to develop cancer. But he added that, there may be entirely different mechanisms driving cancer in young and old people, requiring an adjustment in our view of aging and cancer.