Triple negative breast cancer

Triple negative breast cancer is a subset of breast cancer that is generally more aggressive in nature than other types of breast cancers. It is also more challenging for doctors to treat.

It is characterised by having a lack of hormone (estrogen and progesterone) receptors and the HER2 receptor. The implication of this is that there is a lack of targets for treatments. For example, in patients who have hormone receptor positive breast cancer, estrogen receptor blockers, such as tamoxifen can be used. In patients who have HER2 receptor positive disease, treatments such as targeted therapy trastuzumab can be used. Thus, in triple negative breast cancer, mostly, only chemotherapy can be used for

this reason.

Recently there have been clinical trials running to see the impact immunotherapy on this type of breast cancer. Immunotherapy is different from other therapies in that it uses the body’s own immune system to fight cancer by causing it to be over active. This type of therapy has a different side effect profile from chemotherapy that is related to the immune system. Research on immunotherapy so far have been very promising, but there is still a lot more to be done before they can be approved for use in triple negative breast cancer. Many patients in South Africa are included for enrollment and offered participation in these clinical trials if they meet the eligibility criteria for the trial. These trials, allow patients access to immunotherapy.

A small population of triple negative breast cancers has an androgen receptor, and in some special instances an androgen receptor blocker, such as that used in prostate cancer can be used in patients with metastatic disease.

Triple negative breast cancer has the potential to metastasise or spread early in the disease process to organs such as lungs, liver or also to bone. It is important to stage this triple negative breast cancer before treatment using CT (computerised tomography) or PET (positron emission tomography) scanning.

If triple negative breast cancer is localised to the breast or lymph nodes in the axilla/armpit only, most oncologists prefer to use chemotherapy upfront, before surgery. This is referred to as neo adjuvant chemotherapy. The reason behind this is, that the better response achieved with neo adjuvant chemotherapy the better the long term or overall survival of patients is. Patients who achieve a complete pathological response, meaning that there is no disease detectable after neo adjuvant chemotherapy, are believed to do better in the long run. Recent data shows that patients, who reach a five-year disease free benchmark, generally have a better outcome.

There is different chemotherapy regimens used for triple negative breast cancer, and usually contain a combination of different classes or types of chemotherapy agents. These chemotherapy agents are referred to anthracycline, taxanes or platinum based chemotherapies. Often it is necessary to use injections called GCSF (granulocyte colony stimulating factors) with neo adjuvant chemotherapy, as chemotherapy can cause neutropenia (low white blood cell counts) in patients. This is to prevent infections in patients, as white blood cells are responsible for the patient’s immune system; also it helps to maintain the dose intensity of this treatment.

After neo adjuvant chemotherapy, patients then have potentially curative surgery and if warranted, radiation therapy as well.

When treating metastatic disease chemotherapy can be used as a single agent, meaning one chemotherapy agent alone, not in combination with other agents. When the disease is severe doctors may consider combinations.

The treatment of patients with stage 4 or metastatic triple negative breast cancer is often palliative, meaning that they can no longer be cured, but chemotherapy is used to lessen burden of disease and to alleviate symptoms caused by the cancer and also to improve quality of life. Patients with metastatic disease can also be enrolled in clinical trials.

Triple negative breast cancers are associated with the BRCA gene mutation. Testing for this can be considered in patients with triple negative breast cancer for whom it is relevant, with optimal genetic counseling. The BRCA gene has implications because it accounts for about 20% of hereditary breast cancers and also has an association with other cancers, especially ovarian cancer.

Children of parents who carry BRCA mutations have a 1 in 2 chance of inheriting the mutation as well. The most common populations affected include Afrikaans and Jewish patients.

The BRCA also has treatment implications, as some research has shown that it may be more sensitive to platinum based chemotherapy.

New agents called PARP inhibitors have been recently approved abroad for use in BRCA associated triple negative metastatic breast cancer and are available here in clinical trial settings as well.

Triple negative breast cancer is an important entity to be distinguished from other types of breast cancers as the prognosis is generally poorer, so treatment upfront is more aggressive as we to try and achieve cure.

The important facts about triple negative breast cancer to remember is that:
  • It is more aggressive and has a poorer prognosis than other breast cancers.
  • Because of its lack of receptors, it is generally only treated with chemotherapy.
  • Initial treatment is aggressive in order to aim for pathological complete responses, as survival is better when this is achieved.
  • It can metastasise early and treatment is palliative in this setting. 
  • There is an association with the BRCA mutation.
  • PARP inhibitors can be used in BRCA positive associated patients, but is not yet available in South Africa.
  • Immunotherapy is being investigated as a new alternative to chemotherapy in early and advanced triple negative breast cancers.
  • Patients should consider a clinical trial if one is available and if they meet the criteria for the trial.

Written by Dr Ronwyn van Eeden and Dr Bernardo Rapoport.