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Targeted breast cancer therapies

There is ongoing and extensive research into developing new and better cancer treatments with fewer side effects. This includes breast-cancer targeted therapies.

What are targeted cancer therapies?

Targeted cancer therapies are emerging treatments that target specific characteristics of cancer cells. They are therefore less likely to harm normal, healthy cells. And they generally have fewer side effects than chemotherapy treatments.

Unfortunately, most targeted breast cancer therapies are currently not available in our state hospitals. Many are not yet available in South Africa at all. Those that are available can be very expensive and not all medical aids will pay for them.

Please note: only some medical aids reimburse these drugs. Even then, only in very limited circumstances, where there is good evidence of their activity.

These are some of different types of targeted breast cancer therapies available in South Africa:

HER2 blockers

In about 15% of breast cancers, the cancer cells have a gene mutation that makes an excess of protein HER2 (Human Epidermal Growth Factor Receptor 2). This promotes the growth of these cancer cells. HER2-positive breast cancers tend to be more aggressive than other types of breast cancer.

The good news is that the HER2 receptor can be targeted with certain drugs. These include traztusumab (Herceptin, Ogivri), and pertuzumab (Perjeta):

These work by attaching to the HER2 receptors on the breast cancer cells and blocking them from receiving growth signals.

They are so effective that the prognosis for this aggressive subtype of breast cancer has vastly improved.

They are usually initially given in combination with chemotherapy, but can also be given alone or (sometimes) in combination with endocrine (hormone) therapies.

For more information on Herceptin, click here.

For more information on Perjeta, click here.

Kadcyla is an antibody/drug conjugate. This means that the chemotherapy molecule is attached to the trastuzumab antibody. This approach gives far fewer side effects than conventional treatment, as only HER2-positive cells take up the chemotherapy.

For more information on Kadcyla, click here.

Monoclonal antibodies

Our immune system can attack foreign cells by manufacturing antibodies. An antibody is a protein that can stick to another protein on the foreign cell called an antigen. Once attached, they can help the immune system destroy the cells containing the foreign antigen.

Antibodies can be designed and manufactured in the laboratory to specifically target certain antigens that may be found on specific cancer cells. These are known as monoclonal antibodies.

In general, trying to harness the immune system to fight the cancer is an approach that has worked less well in breast cancer than in some other cancer subtypes – for example, some renal (kidney) cell cancer, some lung cancers and some melanomas.

Examples used to treat breast cancer include:

Trastuzumab (Herceptin) and pertuzumab (Perjeta) which attach to the HER2 receptor, as mentioned above.

Another is bevacizumab (Avastin) which is directed against vascular endothelial growth factor-A. This has shown some positive results in patients with metastatic breast cancer (where the cancer has spread to other parts of the body). Unfortunately, it has not proved to be as effective as first hoped, and is not often used in breast cancer treatment any longer.

Pembrolizumab (Keytruda) shows promising activity against PDL-1 (programmed cell death receptor-ligand). PDL-1 inhibits a pathway that some cancer cells hijack in order to suppress immune control.

This drug may be useful for a subset of patients with triple negative (ER negative, PR negative and HER2 negative) breast cancer.  It is not registered yet in South Africa for use in breast cancer.

For more information on Keytruda, click here.

PARP inhibitors

Poly (ADP-ribose) polymerase (PARP) is an enzyme which helps cells to repair their DNA in event of damage.

People who have BRCA 1 and BRCA 2 mutations in their DNA have an increased chance of developing breast cancer. However, these faulty BRCA genes are less able to repair themselves, and PARP inhibitors reduce this capability even further. This prevents the cancer cells from repairing their DNA and they eventually die.

As a result, breast cancer patients with BRCA mutations and who are HER2-negative may be candidates for this group of drugs.

Drugs used for this purpose include olaparib (Lynparza), talazoparib (Talzenna) and rucaparib (Rubraca)

PARP inhibitors are not licenced for use in breast cancer. However, Olaparib is used in treatment of ovarian cancer.

mTOR inhibitors

Two-thirds of breast cancers are oestrogen-positive (ER+) and may initially be sensitive to hormone therapies such as Tamoxifen and Aromatase inhibitors, as discussed earlier.

In the advanced breast cancer setting, this sensitivity is often present initially, but eventually all cells escape hormonal control.

Sometimes this resistance is due to hyperactivation of the PI3K/PTEN/Akt/mTOR pathway in cell division.

Everolimus (Affinitor) is an mTOR-inhibiting drug that blocks this pathway, causing the cancer cell growth to stop or slow down. It can be offered to post-menopausal women and is given in combination with exemestane (an aromatase inhibitor) in an attempt to overcome resistance to the hormone therapy.

For more information about everolimus/Afinitor, click here.

CDK4/6 inhibitors

Another enzyme that is vitally important for cell division is cyclin-dependent kinase (CDK).

CDK 4/6 inhibitors block this enzyme from stimulating cancer-cell division.

Ribociclib (Kisqali), palbociclib (Ibrance) and abemaciclib (Verzenio) are used currently to treat ER-positive, HER2-negative metastatic breast cancer.

Happily, these drugs are now just becoming available in South Africa (ribociclib is now available as Kryxana), and we expect the others to become available shortly. 

They promise a real advance in our breast cancer armamentarium, and we are very excited to start using them.

Other targeted therapies

Research trials into many other targeted therapies across the world are ongoing. The aim is to find better treatments, to effect better outcomes with fewer side effects.

Our practice is currently recruiting patients into a trial investigating the drug ipatasertib, an ATP competitive inhibitor, in the treatment of  advanced triple-negative breast cancer.

A LAST WORD….

As you can appreciate, treatment of breast cancer is becoming more individualised, and more complicated.

This means that your treatment may be very different to someone else’s treatment, even if your cancers seem initially to be very similar. 

The information available on the internet can be confusing and, worse, sometimes unscrupulous companies make excessive claims about how well their particular product works. 

Please do not hesitate to ask us if something is unclear or confusing – all questions are good questions!

More info

Find out more about  LOCAL TREATMENT FOR BREAST CANCER – surgery and radiotherapy.

Find out more about other  SYSTEMIC TREATMENT FOR BREAST CANCER – chemotherapy, hormone therapy, immunotherapy and biological therapy.

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Phone: (+27) 021 531 6924
Life Vincent Pallotti Hospital / Christiaan Barnard Memorial Hospital / Claremont Pathcare Suites