Breast Cancer Research Advances: Lifestyle Factors, New Therapies, and Postpartum Risk

More than a quarter of healthy years lost to breast cancer are due to lifestyle factors such as red meat intake and smoking, according to the largest study of its kind. The study, published in the Lancet Oncology, used data from population-based cancer registries to produce a comprehensive analysis of breast cancer and its risk factors spanning from 1990 to 2023 from more than 200 countries.

New breast cancer cases in women are predicted to rise by a third globally, from 2.3 million in 2023 to more than 3.5 million in 2050, according to the analysis by the Global Burden of Disease Study Breast Cancer Collaborators. In the UK, about one in seven women will develop the disease in their lifetime.

The findings suggest that maintaining a healthy lifestyle, including not smoking, doing sufficient physical activity, lowering red meat consumption, and having a healthy BMI may prevent more than a quarter of healthy years lost to illness and premature death due to breast cancer worldwide. In 2023, 28% of the global breast cancer burden (6.8 million years of healthy life lost to disability, illness and early death) was linked to six potentially modifiable risk factors. High red meat consumption had the biggest impact (linked to nearly 11% of all healthy life lost), followed by tobacco use including secondhand smoke (8%), high blood sugar (6%), high body mass index (4%), high alcohol use and low physical activity (both 2%).

The analysis found that, globally in 2023, three times as many new breast cancer cases were diagnosed in women aged 55 or older compared with women aged 20-54 (161 cases per 100,000 women, compared with 50). But the rates of new cases in women aged between 20 and 54 have risen by nearly a third (29%) since 1990, while rates in older women have not changed substantially.

While those in high-income countries typically benefit from screening and more timely diagnosis and comprehensive treatment strategies, the mounting burden of breast cancer is shifting to low- and lower middle-income countries where individuals often face later-stage diagnosis, more limited access to quality care and higher death rates.

On the treatment front, scientists are advancing new targeted therapies for metastatic breast cancer. Breast cancer is one of the most common cancers in women, with about one in eight women in the United States alone diagnosed during their lifetimes. Metastatic breast cancer remains a leading cause of cancer-related deaths among women globally and is currently incurable.

One notable advancement in breast cancer treatment over the past decade has been the development of cyclin-dependent kinase (CDK) inhibitors. These drugs work by blocking the activity of specific enzymes—such as CDK4 and CDK6—that play a key role in driving cancer cell growth. They offer a more targeted and tolerable approach compared to traditional chemotherapy, which does not distinguish between rapidly dividing cancer cells and healthy cells.

By leveraging advanced understanding of protein structures, cutting-edge technology, and sophisticated chemical techniques, researchers discovered subtle differences in the enzymes' binding pockets. This breakthrough has allowed them to design a therapeutic candidate, now in a Phase 3 clinical trial, that specifically inhibits CDK4, which offers the potential for more complete and continuous target coverage and may improve tolerability, subject to clinical success and regulatory approval. Researchers believe that CDK6 predominately affects blood cells while CDK4 plays a key role in breast cancer cell cycle division, making it the preferred target for this new approach.

Separate research from the Institut Pasteur reveals how cellular senescence during mammary gland involution after pregnancy may both aid tissue repair and promote postpartum breast cancer. Postpartum breast cancer, diagnosed five to ten years after giving birth, carries a higher risk of metastasis and lower survival rates compared with women who have not been pregnant or those diagnosed during pregnancy.

By studying mammary gland physiology in mice, researchers identified senescent cells specifically appearing during involution, the majority of which were milk-producing alveolar cells. Using pharmacological treatment to selectively remove senescent cells, the researchers confirmed that senescence is essential for normal involution. Without it, tissue remodelling is delayed. The study also showed that senescent cells actively recruit immune cells such as macrophages by secreting signalling molecules, guiding the restructuring of the microenvironment.

The research also discovered the paradoxical role of senescence: while beneficial for tissue repair, it can also be hijacked by tumour cells. Factors secreted by senescent cells enhance the plasticity of cancer cells, allowing them to adapt to environmental changes and spread more effectively. In mouse models of breast cancer, eliminating senescent cells during involution significantly delayed tumour growth and reduced metastasis formation. The study provides a foundation for future drug discovery efforts aimed at developing new interventions for postpartum breast cancer.