An Old Drug's New Mission: Deflate Cancer Risk

Breast cancer is one of the most common and deadliest cancers among women worldwide. Statistics show that over 2 million women are diagnosed with breast cancer each year, with about one-tenth diagnosed at an advanced stage. Of particular concern is the higher prevalence of a subtype known as triple-negative breast cancer among younger women and Black women. This subtype is highly aggressive, has a high recurrence rate, and is difficult to treat. Is it possible to nip cancer in the bud before it even forms?

Recently, a report published in Nature titled "Anti-progestin therapy targets hallmarks of breast cancer risk" provides an exciting answer from scientists at the University of Manchester and other institutions: an already marketed drug may become a "new weapon" in the prevention of breast cancer.

We know that hormones play a crucial role in the development of breast cancer. Besides estrogen, progesterone is also a "lurking master", not only promoting the growth of certain breast cells but also potentially altering the internal environment of the breast, making normal cells more susceptible to "rebellion" into cancer cells. In this study, scientists focused on ullipristal acetate, a drug already used clinically for other gynecological conditions. Could it reduce the incidence of breast cancer in high-risk women by blocking the effects of progesterone?

Between 2016 and 2019, researchers recruited 24 premenopausal women aged 34 to 44 with a family history of breast cancer to participate in a clinical trial called "BC-APPS1". They received 12 weeks of ullipristal treatment and underwent breast biopsies, blood tests, and magnetic resonance imaging (MRI) scans before and after treatment. Researchers employed a multi-dimensional analysis strategy, ranging from imaging to single-cell RNA sequencing, from proteomics to atomic force microscopy, attempting to answer the question from different perspectives: Does this drug alter the "cancer-causing environment" of breast tissue?

The results were promising:

(1) A reduction in "dangerous cells": The drug significantly inhibited the number and activity of luminal progenitor cells, the putative cell of origin of triple-negative breast cancer. A reduction in their number meant that the "seeds" of cancer were effectively cleared.

(2) Decreased mammographic density: MRI results showed that the fibroglandular volume decreased after treatment, indicating a decrease in mammographic density; high mammographic density is a known risk factor for breast cancer.

(3) "Softer" tissue and "loosened" collagen: Researchers observed a significant reduction in collagen VI within the breast tissue after treatment, leading to a more looser tissue structure and decreased tissue stiffness. This means that the "physical environment" of the breast is no longer as suitable for cancer cell survival and growth.

(4) Disruption of cell-matrix "dialogue": The study revealed for the first time that collagen VI is spatially closely associated with luminal progenitor cells. As the drug reduced collagen stiffness, the activity of these dangerous cells also declined. In other words, the drug not only targets the "bad cells" but also transformed the "adverse soil" they depend on.

Why is this study considered "cutting-edge"?

1. Drug repurposing with rapid translation potential: Ulipristal acetate already has clinical safety data. If subsequent trials confirm its anti-cancer effects, the time to market could be significantly shortened.

2. Multi-omics + Imaging: ushering in a "precision era" for cancer prevention: This study integrated cutting-edge technologies such as imaging scanning, single-cell sequencing, and proteomics, not only answering "whether it works" but also revealing "why it works".

3. A paradigm shift from "treating disease" to "preventing disease": The study offers a new approach to "cancer prevention"-reversing the situation before carcinogenesis by regulating hormone signaling and the matrix microenvironment.

Dr. Sacha Howell, one of the researchers, stated, "We are incredibly grateful to every woman who participated in this study. Their courage has shown us that blocking progesterone signaling may be an effective strategy for preventing breast cancer. Most excitingly, we found that the drug can remodel breast tissue structure and reduce collagen stiffness, providing a completely new perspective on the mechanisms of cancer prevention."

Although this study had a small sample size and larger-scale clinical trials are needed to validate the results, it undoubtedly shines a light on breast cancer prevention, especially for high-risk young women.

Reference:

1. Simões, B.M., Pedley, R., McCloskey, C.W. et al. Anti-progestin therapy targets hallmarks of breast cancer risk. Nature (2025).