Diagnosis | What is triple-negative breast cancer?

Diagnosis

Most tumors are palpated by the patients themselves. Since the tumor can grow very quickly, it is usually not detected by normal breast cancer screening if it develops in the time in between. Since mainly younger patients are also affected, mammography (X-ray image of the breast) is usually not very well suited because the glandular tissue of the breast is still very dense in these patients.

In sonography (ultrasound), the tumor usually does not present itself as a classic malignant tumor, but rather as a benign change, which is why it can be misjudged. Magnetic resonance imaging is the most sensitive method (up to 100%) for the detection of a triple-negative tumor in the breast, but even here the tumors can present themselves as benign lesions, such as cysts. The diagnosis is nevertheless primarily made by means of mammography and ultrasound; in the case of ambiguous findings, an MRI of the breast is still connected.

A biopsy of the breast (tissue sampling) must always follow to confirm the diagnosis by a pathologist. The tissue sample is necessary to differentiate between the different types of breast cancer, which is also crucial for the therapy. In triple-negative breast cancer, immunohistochemistry (a special procedure to stain certain structures and proteins under the microscope) does not find any relevant expression of hormone receptors (progesterone receptor and estrogen receptor) and the receptor for the human epidermal growth factor. However, the growth patterns may vary considerably within the tumor form, which is also relevant for prognosis.Therefore an examination by the pathologist is crucial for the further procedure.

Therapy for triple-negative breast cancer

The therapy of triple-negative breast cancer consists of several parts. First, a biopsy (tissue sample) is usually taken from the so-called sentinel lymph node to determine whether the lymph nodes are already affected. Then, the breast cancer is fitted with clips so that it is possible to know where the tumor was later.

This is used because after a systemic therapy with chemotherapeutic agents, the tumor mass can be significantly reduced. Chemotherapy is recommended in this case, as it leads to a better operability of the tumor afterwards and even to a pathological complete remission through chemotherapy. This means that the tumor can no longer be detected by the pathologist afterwards.

If this occurs, patients have a very good prognosis after subsequent surgery. The operation can be performed in two different ways. Firstly, a complete removal of both breasts can be performed and then reconstructed cosmetically.

Here the results of the reconstruction are usually better, because a symmetrical reconstruction is achieved. This operation is usually recommended especially for patients with hereditary breast cancer. However, breast-conserving surgery can also be performed as an alternative.

In this case, however, the breast must be additionally irradiated, and if more than two lymph nodes are affected, the lymph node region must also be irradiated. Radiation therapy reduces the risk of local recurrence (recurrence of a tumor at the same site) by 50% and thus many patients can be cured permanently. In addition, removal of the ovaries is indicated in patients with BRCA mutation (see: breast cancer gene), as this reduces mortality from breast cancer by 62% and from triple-negative breast cancer by 93% and, of course, also reduces the risk of ovarian cancer.

Neoadjuvant chemotherapy (chemotherapy before surgery to reduce the amount of tumor) is highly recommended for triple-negative breast cancer, as it is very aggressive and fast-growing and therefore usually responds very well to chemotherapy. The standard composition of chemotherapy consists of anthracyclines and taxanes, either in combination or sequentially. This combination provides complete pathological remission (tumor is no longer detectable from following the path) in some patients, which has an excellent prognosis.

The part of patients who do not have complete pathological remission has a worse prognosis. For this reason, new combinations of chemotherapeutic agents are currently being investigated for these patients. Here, the additional administration of capecitabine or carboplatin has shown good results (improvement in remission from 30% to 50%).

However, more chemotherapeutic drugs also have more side effects and therefore the higher quantity must always be weighed up carefully. In general, there are indications that a good prognosis can be achieved for more patients in the future through extended chemotherapy. Currently, there is no targeted therapy (antibody or immunotherapy) for triple-negative breast tumors.

However, there are substances that are currently being investigated in clinical studies. The first substance is the PARP inhibitor olaparib. PARP inhibitors inhibit the enzyme poly-ADP-ribose polymerase and thus should prevent the tumor from repairing DNA damage caused by chemotherapy.

It is intended to be used in patients with BRCA mutation and triple-negative breast cancer after surgery. Another substance is the antiandrogen enzalutamide. It is to be applied in triple-negative breast cancer with expression of androgen receptors (50%). Both show promising results in clinical studies and may be available in the near future as a targeted therapy for triple-negative breast cancer.