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Africa: Breast cancer: why it’s hard to treat and what new approaches are on the horizon

Monicel
Africa: Breast cancer: why it’s hard to treat and what new approaches are on the horizon

Breast cancer is the number one cancer among women, with more than 2 million cases diagnosed worldwide in 2022. It is also particularly difficult 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 tumors 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 and forming tumors.

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

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

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

Most cancers can be prevented through a healthy lifestyle and regular exercise.

What are the different types of tumors?

For breast cancer, tumors 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 the abnormal cells are limited to the milk ducts only.

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

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

Triple negative breast cancer (TNBC): 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 difficult to treat.

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

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

What makes breast cancer so difficult to treat?

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

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

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

The tumor microenvironment shapes tumor behavior. Some cells in this environment can protect 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, hormone treatments, and targeted therapies.

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

Metastasis, or the spread of cancer to other organs, is another major obstacle. Metastatic cells often behave differently than cells in the primary tumor. This is true for all cancers.

Finally, breast cancer cells sometimes escape detection by the immune system. Normally, the immune system would recognize and attack the 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 such as melanoma, non-small cell lung cancer, kidney cancer and certain lymphomas, especially those with a large number of genetic mutations that make them more visible to the system immune

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 recognize as foreign.