Study challenges dogma about how most breast cancers occur

genetic inheritance influences the type of breast cancer and its prognosisaccording to a Stanford Medical University study that analyzed thousands of tumors and challenged the dogma that most of these cancers arise from random mutations that accumulate throughout life.

For the first time it has been confirmed that genetic sequences inherited from parents – what are they? known as the germline genome– take an “active part” in immunosurveillance and the types of somatic or sporadic (non-hereditary) mutations that may contribute to the occurrence of cancer.

That is, they have an influence in determining whether cells carrying mutations are Potentially carcinogenic substances are recognized and eliminated by the immune system or go undetected and become an incipient cancer.

Findings that could help better predict and control breast tumors are published in the journal Science in a paper that describes a new class of biomarkers for predicting tumor progression and how to predict it.completely new’ to understand the origin of this cancer.

With the exception of a few “highly penetrating” genes that confer significant cancer risk, the role of hereditary factors remains poorly understood, and most cancers are thought to arise from random errors during cell division or from bad luck, said Christina Curtis, study author. work (only 5-10% of breast cancer cases are considered hereditary).

“This would mean that the occurrence of the tumor is random, but that is not what we observed. In contrast, we found that the path of tumor development is limited by hereditary factors and immunity,” he adds in a statement from the Stanford Institute of Medicine. (USA).

Curtis explains that his team had already postulated in 2015 that some tumors are “born bad,” meaning that their malignant and even metastatic potential is determined early in the disease, but these discoveries shed “entirely new light.” ‘ about how early this happens.

Options that move threads

Currently, only a few high-profile genetic mutations associated with cancer are used to predict cancer.

These are the BRCA1 and BRCA2 genes, which occur in one in every 500 women and are associated with an increased risk of breast or ovarian cancer, as well as rarer mutations in the TP53 gene, which causes Li Fraumeni syndrome, which predisposes to childhood and adult tumors. .

New discoveries show that there are dozens or hundreds of additional genetic variants found in healthy people that pull the strings that determine why some people remain cancer-free throughout their lives and others do not.

Researchers studied almost 6,000 breast tumors in different countries. disease stage to examine whether each tumor subtype correlates with patients’ germline oncogenic sequences.

“We wanted to understand how inherited DNA can shape tumor evolution“Read more by Kathleen Houlahan, another contributor.

Among other things, they found that in the initial, preinvasive phase, a large number of epitopes—the part of the molecule that would be recognized by the antibody—protect against cancer, Houlahan said.

But once they have to fight the immune system and develop mechanisms to overcome it, tumors with high levels of germline epitopes become more aggressive and prone to metastasize. The picture, he concludes, changes as the tumor progresses.

“Essentially, there is a tug-of-war between the tumor and the immune cells.“Curtis notes that in a preinvasive setting, the emerging tumor may initially be more susceptible to immune surveillance and destruction. “In fact, many tumors are likely to be eliminated this way and go undetected.”

However, “the immune system doesn’t always win” and some tumor cells may not be destroyed.

Ramon Salazar, head of the department of medical oncology and director general of the Catalan Institute of Oncology, believes that this study, in which he is not involved, is “of excellent quality and very innovative” because the hypothesis demonstrated breaks the paradigm.

For the first time, it was discovered that inherited genetic structure influences immunosurveillance and the types of somatic or sporadic mutations that may contribute to cancer, he tells Science Media Center Spain, a science resource platform for journalists.