Triple-negative breast cancer: new hope

Breast cancer is the most common form of cancer in women and alone accounts for 19% of cancers that affect women.

“Breast cancer is classified into three types, defined by the type of receptors expressed by the cancer cells. These receptors define the therapeutic approach to be used, since they constitute real targets to be hit by drugs,” explains Dr. Giampaolo Bianchini.

There are tumors that express estrogen or progesterone receptors and therefore can benefit from hormonal therapies.

Then there are the so-called HER2-positive tumors, which have receptors for a growth factor (the HER2 protein) capable of fueling its proliferation. These tumors can be treated with monoclonal antibodies and small molecules, developed to bind to HER2 receptors.

Finally, there are triple negative tumors, which do not have receptors for estrogen, progesterone, or HER2 protein: these tumors have no target to hit. That's why of all breast cancers, of which they make up only 15%, they are the ones with the highest mortality.

Until recently, the only means available against triple-negative breast cancer were chemotherapy, surgery and radiotherapy.

A series of recent studies have established the effectiveness of new drugs’ class called immunotherapics, in particular immune checkpoint inhibitors.  The finding was awarded the Nobel Prize for medicine in 2018 for the discovery that the immune checkpoint inhibitors work "by taking the brakes off" the immune system.

In fact, combination of a chemotherapy (called nab-paclitaxel) and an immune checkpoint inhibitor (atezolizumab) has recently been approved as the first line treatment of the metastatic disease.

“At the moment, therapy is only for tumors that express the PD-L1 protein on their surface. Thanks to this protein the tumor is able to inhibit the action of the immune system on what atezolizumab acts. But our goal is to go further. We want to verify the effectiveness of the drug on the earliest stages of the disease, before surgery, and to better understand how the drug works and how to increase the number of patients who can benefit from it,” explains Dr. Bianchini.

The data obtained from the NeoTRIP study, involving 260 women, are very promising. For example, by analyzing biopsies after just one therapeutic cycle, that is, a few weeks after the start of a treatment, the researchers found no trace of tumor tissue in a third of the patients.

Moreover, about two out of three patients with initially PD-L1 negative tumors became positive for PD-L1, indicating that the drug could also be effective for these patients, as already suggested by other studies. Now it necessary to identify in which patients this response is obtained and why.

In the NeoTRIP study researchers have collected some evidence on what distinguishes patients for whom the immunotherapy treatment is more effective. It was done by analyzing tumor biopsies taken at the start of therapy, while the treatment was in progress and during the surgery.

“In addition to the expression of the PD-L1 protein, to which the drug binds, another important indicator of the efficacy is the number of infiltrating lymphocytes in the tumor tissue: the more lymphocytes from the beginning, the more effective the therapy will be.

Next step is to expand our ability to analyze cancer cells, to understand what are the genetic and molecular characteristics that make them more or less sensitive to immunotherapy, including new generation of genetic sequencing techniques,” concludes Dr. Bianchini.