Disease stage, biological characteristics, and aggressiveness of breast cancer
- NOT ALL BREAST CANCERS ARE THE SAME -
The prognosis of breast cancer and the final outcome of the disease depends on two major parameters:
1) disease stage
2) tumor biological characteristics.
First, a few words about breast cancer course and prognosis. Breast cancer is usually diagnosed in the so-called locoregional phase, when we can diagnose only the primary tumor in the breast and possibly the lymph nodes in the armpit affected by the tumor, while metastases on distant internal organs (liver, lungs, bones, brain) are not present or cannot be diagnosed at that moment by standard diagnostic means. However, the possibility of diagnostically undetectable micrometastases is not excluded. In this phase, tumors and axillary lymph nodes are treated, and preventive and anti-tumor drugs are given to act on potentially present distant micrometastases.
From this point on, the disease course can go in two directions:
1) the patient lives on like a healthy individual, and the disease never reappears in any form for the rest of their life;
2) at some point, the disease reappears (relapse), either in the locoregional area or as distant metastasis. The disease can return quite quickly, literally within a few months, or several years and even decades after the primary treatment. Relapse requires appropriate new treatment, and further disease course depends on the success of that treatment. A disease over which therapeutic control is lost ends in death in a short period of time.
The prognosis is indicated by the degree of probability that the disease will have a favorable or unfavorable course. It depends on the disease stage and the tumor’s biological aggressiveness. The more advanced the stage and the more aggressive the tumor, the worse the prognosis. It is expressed as a percentage of patients who survive or are disease-free 5 or 10 years following the diagnosis. Patients in stage Ia and with favorable biological characteristics of the tumor have a 100% five-year survival rate, while with increasing stages, the percentage decreases to about 22% for stage IV.
The larger the tumor, the more affected lymph nodes, the more metastases present on distant organs, the more advanced the disease stage and the worse the prognosis.
The disease stage is categorized from I (initial) to IV (advanced – distant metastases present). It is determined by the tumor size, the number of affected lymph nodes in the armpit, and the presence of distant metastases (the so-called TNM system). The larger the tumor, the more affected lymph nodes, the more metastases present on distant organs, the more advanced the disease stage and the worse the prognosis. The disease stage predominantly depends on the time: the longer the period from the onset of the disease to the start of treatment, the more time the tumor has to grow and metastasize, and the stage will be higher. It partly depends on biological characteristics, as more aggressive tumors grow faster and can reach more advanced stages in a shorter time. This is the basis for the therapeutic effect of early detection and early treatment of breast cancer.
Biological characteristics of tumors. It has long been noticed in clinical practice (way before the discovery of immunohistochemical parameters used in cancer profiling today) that not all cancers are the same in terms of their biological potential: some tumors grow slowly, can reach large dimensions without metastasizing even in regional lymph nodes, while others grow quickly, with distant metastases even when the tumors are rather small, and these metastases also proliferate quickly and lead to death after a relatively short time. Due to the lack of objective parameters, the disease stage based on the TNM system was the only prognostic category for a long time. Over the past thirty years, objective parameters determinable by histological and immunohistochemical analyses of tumor cells have been defined, based on which we can approximately determine the biological aggressiveness of the tumor and the type of therapy that will work best for that type of tumor. The most widely used parameters of this type today are Estrogen and Progesterone receptors, Her 2 receptors, and proliferative factor Ki 67.
It has long been noticed in clinical practice that not all cancers are the same in terms of their biological potential.
There are several possible combinations of these parameters, which could be simplified as follows:
1) Biologically less aggressive tumors have receptors for Estrogen and Progesterone (so-called Er and Pr positive), do not have Her 2 receptors (Her 2 negative), and have a low Ki 67 index (less than 14%). Such tumors are sensitive to hormonal therapy (most often the drug Nolvadex) and respond less well to chemotherapy.
2) Biologically aggressive tumors do not have receptors for Estrogen and Progesterone (so-called Er and Pr negative), have significant Her 2 receptors (so-called Her 2 positive), and high Ki 67 (over 20%). Hormonal therapy has no effect on these tumors, and they are more sensitive to cytostatics than the first group.
3) Another biologically aggressive group of breast cancers is characterized by that both the hormone receptors for Er and Pr, and Her 2 receptors are negative (so-called “triple negative” tumors). In the therapeutic sense, it is similar to the previous group.