Why it is difficult to treat breast cancer and what new approaches are on the horizon

Breast cancer is the number one cancer among women: more than 2 million cases were diagnosed worldwide in 2022. It is also particularly challenging to treat. Physiologist Anna-Mart Engelbrecht, who heads the Cancer Research Group at Stellenbosch University, explains why this is so and how precision medicine could help.

How do tumours work?

Normally, cell growth, cell division and cell death are tightly regulated processes. But mutations in a cell’s DNA can disrupt this regulation, leading to abnormal cell proliferation, forming tumours.

Tumours can be benign (non-cancerous) or malignant (cancerous). Malignant tumours are dangerous because they invade surrounding tissues and can metastasize (spread) to other body parts, such as bones, liver or lungs.

Cancer cells can evade the immune system, create their own blood supply (angiogenesis), and adapt to survive under different conditions, such as low oxygen or treatment pressure.

Only 5%-10% of all cancers arise from germline (inherited) mutations, which are present in all cells of the body from birth, predisposing the individual to developing cancer.

Most cancers are preventable through a healthy lifestyle and regular exercise.

What are the different types of tumours?

For breast cancer, the tumours can be classified into types:

Ductal carcinoma in situ (DCIS): Non-invasive cancer (meaning it has not invaded the underlying tissue beneath the epithelial cells, and abnormal cells are confined only to the milk ducts.

Invasive ductal carcinoma (IDC): The most common type, where cancer cells break through the duct walls (the cells lining the ducts become cancerous) and invade surrounding breast tissue.

Invasive lobular carcinoma (ILC): Begins in the milk-producing lobules and invades nearby tissue. (The lobules are the part of the breast which produce milk. They are anatomically different from the ducts, which transport the milk to the nipples.)

Triple-negative breast cancer (TNBC): The breast tissue lacks estrogen receptors, progesterone receptors, and HER2 protein receptors that control how cells grow and divide. Triple-negative breast cancer is often more aggressive and more challenging to treat.

HER2-positive breast cancer: Overexpression of the HER2 protein, which promotes cancer cell growth.

Hormone receptor-positive breast cancer: Cancer that grows in response to hormones like estrogen or progesterone.

What makes breast cancer so difficult to treat?

Breast cancer is particularly challenging to treat because there are so many subtypes with unique genetic and molecular characteristics.

These variations mean that a treatment effective for one subtype might not work for another. The approach has to be tailored for each patient’s breast cancer.

Another challenge is the tumour microenvironment. Cancer cells “hijack” the normal cells in this microenvironment to sustain cell growth.

The tumour microenvironment shapes tumour behaviour. Certain cells in this environment can shield cancer cells from therapies, making treatment less effective.

Drug resistance further complicates treatment. Over time, breast cancer cells can adapt and develop resistance to chemotherapy, hormonal treatments and targeted therapies.

This adaptation can involve genetic mutations or the use of alternative signalling pathways that allow the cancer cells to continue growing despite treatment efforts.

Metastasis, or the spread of cancer to other organs, is another major hurdle. Metastatic cells often behave differently from those in the primary tumour. This is true for all cancers.

Lastly, breast cancer cells sometimes escape detection by the immune system. Usually, the immune system would recognise and attack abnormal cells. But some breast cancer cells can disguise themselves or suppress the immune response.

This makes immunotherapy less effective. Unlike traditional therapies such as chemotherapy, immunotherapy enhances the immune system’s natural ability to fight cancer.

Immunotherapy has shown success in treating cancers like melanoma, non-small cell lung cancer, kidney cancer and certain lymphomas, particularly those with a high number of genetic mutations that make them more visible to the immune system.

But immunotherapy is not universally effective. Response rates can vary greatly between patients, and side effects can be severe.

Breast cancer tends to have fewer genetic changes for the immune system to recognise as foreign.

How would precision medicine make a difference?

Precision medicine takes into account the genes, environment, and lifestyle of each person and tailors treatments to a tumour’s genetic and molecular characteristics.

It enables targeted therapies that improve efficacy and reduce unnecessary side effects.

Ongoing monitoring through techniques like liquid biopsies (for example a blood test) allows treatment strategies to be adapted as the tumour evolves, and identifying genetic predispositions aids in early detection and prevention.

Precision medicine has transformed cancer care, particularly in cancers like breast, lung, and melanoma, where targeted therapies guided by genetic profiling are now routine for patients who can afford it.

Research and clinical trials continue to expand the reach of precision medicine, promising more effective, individualised treatments for a broader range of patients in the future.