Pulmonary arterial hypertension (PAH) is a rare and severe lung disease in which the blood vessels in the lungs progressively narrow. As a result, the heart must pump harder to move blood through the lungs, which can ultimately lead to heart failure. PAH occurs significantly more often in women and is frequently life-threatening. A new international study now points to a previously underappreciated link between PAH and breast cancer. The findings, published in the journal Circulation, suggest that both diseases may be connected through shared biological mechanisms.
A shared genetic factor
At the center of the study is a gene called BMPR2, which plays a key role in regulating cell growth and inflammatory responses. Mutations or reduced activity of this gene are the most common known genetic cause of PAH. The researchers, including DZL investigator Sébastien Bonnet, who conducts research in Québec and at the Cardio-Pulmonary Institute of Justus Liebig University Giessen, analyzed large international cancer databases and found that BMPR2 activity is markedly reduced in many breast tumors. Tissue samples from breast cancer patients also showed a deficiency of the corresponding protein. These findings suggest that BMPR2 is not only crucial for lung health but may also play a protective role in breast cancer.
Animal model reveals inflammatory mechanism
In additional experiments, the team studied a rat model with impaired BMPR2 function. These animals developed breast tumors more frequently than healthy controls. Notably, the presence of breast tumors was accompanied by a worsening of pulmonary vascular disease. The researchers showed that tumors release pro-inflammatory signaling molecules. One of these molecules — interleukin-1β, a potent inflammatory mediator — stimulated abnormal growth of vascular smooth muscle cells in the lungs, thereby aggravating pulmonary hypertension. In simplified terms, tumor-driven inflammation acted as a “second hit” that exposed an underlying genetic susceptibility.
Nationwide French data support the link
To determine whether this effect is also observed in humans, the team analyzed health data from more than one million individuals in the French national database. The results showed that patients with PAH developed breast cancer at roughly twice the rate of the general population. Conversely, PAH occurred nearly three times more often in breast cancer patients. This bidirectional association suggests that the two diseases may influence each other, potentially through shared inflammatory processes and disrupted BMPR2 signaling pathways.
Implications for medical practice
The study does not establish a direct cause-and-effect relationship but highlights an important potential risk. Increased awareness could help physicians monitor PAH patients more closely for breast cancer — and vice versa. In the long term, the findings may also open new therapeutic avenues. If inflammatory processes play a central role, anti-inflammatory strategies could help slow the progression of pulmonary hypertension. The researchers view their results as a starting point for further clinical studies aimed at better identifying and protecting at-risk populations.
Originalpublikation: Toro V et al. Breast Cancer Reveals Latent BMPR2-Related Susceptibility to Pulmonary Hypertension. Circulation. 2026 Jan 28. doi: 10.1161/CIRCULATIONAHA.125.079067. Epub ahead of print. PMID: 41603037.
