Triple Negative Breast Cancer (TNBC)
Triple Negative Breast Cancer (carcinoma)│ Personalized breast cancer treatment, tailor-made for each woman based on genomic tests, is a new treatment method introduced by Israeli oncologists that can significantly change the results of treatment for triple negative breast cancer.
Triple negative breast cancer is a type of cancer that is usually characterized by the appearance at a younger age and a higher aggressivenedd than other malignant diseases of the breast. Nevertheless, to date, there are almost no unique programs for treating women suffering from this disease in the world.
New diagnostic methods based on genomic analyzes give Israeli oncologists the opportunity to change the situation.
What is thriple negative breast cancer?
About 10-25% of women with breast cancer are diagnosed with its subtype, known as triple negative cancer. This is because this type of cancer is negative for the 3 cell markers that are being studied in breast cancer.
As a subgroup of breast cancer, triple negative cancer has many unique characteristics, such as: early age, more intense course of the disease and sometimes resistance to some of the most effective therapies for other types of breast cancer.
Despite these common characteristics, there are still large deviations in different patients. As a rule, all patients with triple negative breast cancer are divided into 7 subgroups of diseases, which differ in their characteristics.
Previously, despite such variations, treatment for most patients with triple negative cancer, as well as other patients diagnosed with breast cancer, did not differ significantly. At present, the technology of genomic analysis brings us closer to the day when every woman with triple negative breast cancer will be treated individually, using progressive immunotherapy and other methods of treatment.
Biological basis of triple negative breast cancer
As already mentioned, triple negative cancer has its name due to the fact that its tumor cells are negative to 3 cell markers: estrogen receptor hormones (ER), progesterone hormone receptors (PR) and HER2 / Neu receptors. The negative growth of these markers is usually determined by demonstrating a positive percentage of less than 1% in immunohistochemistry (IHC) and FISH tests.
These 3 receptors play an important role in the development of breast cancer, and therefore their treatment can be effective. However, with this type of cancer, receptors do not play a role in stimulation or maintenance of the disease, so the standard treatment of these receptors is ineffective in triply negative cells.
While science does not know the cause of breast cancer, as well as other types of cancer, it is known that the BRCA1 mutation is three times more common in patients with a triple negative type of cancer.
Survival and prognosis for triple negative cancer
Following advanced diagnostic methods, most women with breast cancer of all types are diagnosed at an early stage, which provides excellent survival for 5 years or more. Even if the disease has spread to local lymph nodes, 5-year survival is still considered very high, and is about 85%.
It is difficult to say the same for three times negative breast cancer, this type of cancer is more aggressive than other breast cancers. This disease appears at an earlier age, characterized by a larger tumor size at the time of diagnosis, and sometimes a large spread to neighboring lymph nodes.
In a ten-year study in Canada, involving approximately 1,600 female patients, it was found that three patients with triple negative breast cancer had a double chance of recurrence after treatment, 5 years after diagnosis, but no later than . In other words, the risk of recurrence of the disease reaches a peak of one to three years from the diagnosis, and then the risk for negative triplets is comparable to the risk for all patients with breast cancer. In addition, with triple negative breast cancer the main protective factor against the progression of the disease is early diagnosis.
Please note that these data are average for large groups of patients, and that the risk of each patient depends on many factors, including the size of the tumor, the number of affected lymph nodes and other characteristics.
Therapeutic value of triple negative cancer
As already mentioned, triple negative type of breast cancer does not contain estrogen or progesterone receptors and HER2 receptors, so drugs against these receptors are not effective, as compared to other types. For example, often used drugs for the treatment of breast cancer are intended to prevent the creation of estrogen by inhibiting the protein that produces it – aromatase. This group of drugs is called aromatase inhibitors and it is not effective for treating a triple negative type of cancer whose tumors do not absorb estrogen.
Another drug that is also ineffective in triple negative breast cancer, for the same reason, is Herceptin. This drug works specifically on the HER2 receptor.
In 2019, the FDA approved the first immunotherapy protocol, atezolizumab (Tesanteric) and Nab-Paclitaxel (in combination with chemotherapy). It shows good efficacy in triply negative breast cancer, increasing the life expectancy of such patients, including those with an expression level of PD-L1 greater than 1%.
With the exception of these differences, the therapeutic approach to triple negative breast cancer is almost identical to that of other forms of breast cancer: surgical intervention will be preferred, followed by radiation therapy and chemotherapy.
Patients with triple negative breast cancer, a tumor larger than 0.5 cm, or involved lymph nodes are often recommended postoperative chemotherapy because of the increased recurrence risk and the lack of HER2 or hormone therapy.
Immunotherapy and triple negative breast cancer
Immunotherapy (immunological treatment) is a drug that improves the body’s natural immune response to cancerous tumors, usually by improving the detection of tumors by the immune system. Immunotherapy works against specific mechanisms of camouflage on cancer cells, so cells that do not use these mechanisms are immune to immunotherapy.
One of the most common drugs for immunotherapy is Keytruda. This drug has achieved breakthrough results in the treatment of skin, lung, neck and many other cancers. Keytruda is based on inhibition of camouflage protein PD-L1, which is found on some cancer cells, and therefore the drug is active only against these cells. Recently, at the historical stage, the FDA (United States) approved the drug for the treatment of any cancer that is determined positive for PD-L1, regardless of its type.
Preliminary studies, which were also shared by Israeli researchers, showed that about 60% of patients with triple negative breast cancer were positive for this protein by 1%, which suggests that the treatment of Keytruda patients with triple negative breast cancer also benefits. The initial results of these studies indicate acceptable safety of treatment, although the long-term benefits of this treatment are not yet clear. At the moment, studies of Keytruda and other drugs continue to test the benefits of these methods for treating negative triplet cancer cells.
Genomic mapping and triple negative breast cancer
Recent studies using genomic analysis have identified new targets for treatment, not only for proteins on cancer cells, but also for unique genes in the DNA of these cells. The genes for treatment are PTEN and PIK3CA, each of which is expressed in 10% of negative triple tumors. In some types of negative triple cancer types, these mutations can occur in about half of the patients, which gives our doctors the opportunity to reverse the treatment of these women.