Spanish researchers have identified a molecular signature that can predict which precancerous breast lesions are likely to progress to invasive cancer, a breakthrough that could spare thousands of women from unnecessary surgeries and treatments. The discovery, led by scientists at the Spanish National Cancer Research Centre (CNIO), focuses on distinguishing between lesions that remain benign and those with a high risk of malignancy — a critical challenge in breast cancer screening and early intervention.
Currently, when mammograms or biopsies detect abnormal cell growth in the breast — such as atypical ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS) — clinicians face a challenging dilemma. While some of these lesions may never become cancerous, others will progress to invasive ductal or lobular carcinoma. Because it’s impossible to tell which is which with certainty today, many women undergo aggressive treatments like surgery, radiation, or hormonal therapy as a precaution, exposing them to physical, emotional, and financial burdens that may not be medically necessary.
The CNIO team’s research, published in Nature Communications, analyzed tissue samples from over 300 patients with diagnosed precancerous breast lesions. Using advanced genomic profiling and machine learning algorithms, they identified a specific pattern of gene expression — involving 17 key biomarkers — that reliably predicted which lesions would evolve into tumors within a five-year window. The signature demonstrated an accuracy rate of over 90% in validation cohorts, significantly outperforming current histopathological assessment methods.
“This isn’t just about detecting cancer earlier — it’s about understanding which early changes truly threaten health and which can be safely monitored,” said Dr. Miguel Ángel Quintela-Fandino, head of the CNIO’s Breast Cancer Clinical Unit and senior author of the study. “We’re moving from a one-size-fits-all approach to precision prevention, where interventions are tailored to individual risk.”
The findings could reshape clinical guidelines for managing high-risk breast lesions. If validated in larger, prospective trials, the biomarker test might allow doctors to recommend active surveillance for low-risk lesions — similar to protocols already used in prostate cancer — while reserving intensive treatment only for those with high molecular risk.
Breast cancer remains the most commonly diagnosed cancer among women worldwide, with over 2.3 million new cases reported in 2022 alone, according to the World Health Organization (WHO). While mortality rates have declined in high-income countries due to improved screening and treatments, overtreatment of precancerous conditions continues to be a significant concern in oncology.
Experts outside the study have expressed cautious optimism. “This kind of molecular risk stratification is exactly where breast cancer prevention needs to go,” said Dr. Isabelle Thomassin-Naggara, a breast radiologist at Gustave Roussy Cancer Campus in Paris, who was not involved in the research. “But we need to see how this performs in real-world screening programs, across diverse populations, and whether it integrates smoothly into existing pathology workflows.”
The CNIO researchers are now preparing for a multicenter validation study across hospitals in Spain and Portugal, aiming to test the biomarker panel in routine clinical settings. They also plan to explore whether the same approach could apply to other precancerous conditions, such as cervical intraepithelial neoplasia or colorectal polyps.
For patients, the implications are deeply personal. Avoiding unnecessary surgery means preserving breast tissue, reducing recovery time, lowering infection risks, and sparing women from the anxiety of undergoing cancer treatment when it may not be needed. It also has the potential to reduce healthcare costs associated with overtreatment — estimated to account for up to 30% of breast cancer-related expenditures in some health systems.
As precision medicine advances, tools like this molecular signature represent a shift toward smarter, more individualized care. Rather than treating all abnormalities as potential threats, clinicians may soon be able to distinguish true danger from benign change — offering peace of mind to many and targeted help to those who truly need it.
The next step is awaiting results from the ongoing validation trial, expected to conclude in late 2025. Until then, women with precancerous breast findings should continue to follow their physicians’ recommendations, which are based on the best available evidence today.
What are your thoughts on this development? Have you or someone you understand faced uncertainty after a breast lesion diagnosis? Share your experience in the comments below — your story could help others feel less alone. If you found this information useful, consider sharing it with friends or family who might benefit.