Breast cancer cells can spread through the body in the lymphatic system, the blood system or by direct growth into surrounding tissues.
The axillary lymph nodes are the first location where cancer cells may be held back, once they move from the primary breast tumor site. These lymph nodes are located in the armpit or along the chest wall lymphatics. From there cancer cells can spread into the venous system, and give rise to metastases in different organs: skeleton, lungs, liver, brain and soft tissues. Direct spread to the blood stream is also possible.
It is believed that breast cancer is often already a systemic disease at the time of diagnosis, meaning that there are already micrometastases throughout the body. Therefore there is a need to administer both locoregional treatment with surgery and radiotherapy, and adjuvant systemic therapy. This systemic treatment aims to destroy any micrometastases and thus avoid later relapse of the disease.
At the time of diagnosis of a breast cancer, proper staging is mandatory to determine the spread of the disease, the prognosis and the need for adjuvant treatment. The staging uses the TNM System, where T stands for tumor size, N for the status of the axillary nodes (whether or not they are affected), and M for the presence or absence of distant metastasis.
Tumor size (T)
Tumor size is correlated with prognosis (the larger the tumor, the worse the prognosis), but also with the status of the axillary nodes (the larger the tumor, the greater the chance of affected axillary nodes). Tumors of less than 1 cm usually have a good prognosis.
Lymph nodes status (N)
The axillary nodes are the primary, and usually first place of lymphatic drainage from the breast. The number of positive (or affected) axillary nodes is the main prognostic factor. The significance of so-called micrometastases in the axillary nodes (foci of tumor cells with a diameter <2 mm) is presently not well known. The table below shows the chances of developing a recurrence according to the status of the axillary lymph nodes.
|N° of positive axillary nodes
|Disease free survival at 5 years
|Overall survival at 10 years
Presence or absence of distant metastasis (M)
If there are no proven metastases, adequate loco-regional treatment and drug therapy are curative. If metastases are detected in other organs, using conventional radiographic techniques, such as abdominal ultrasound and isotopic analysis of the skeleton, this means that the disease is incurable. The duration and quality of life can however be improved with different types of medication.
Prognostic factors are those factors at the time of diagnosis that give additional information about the potential outcome of the disease (risk of relapse, risk of death) and determine the need for adjuvant treatments.
The main prognostic factors are:
- Histological grading, nuclear and histological grading: Grade I-II-III. The higher the grade, the poorer the differentiation and the worse the prognosis. This is determined by microscopic examination of the tissue removed.
- Hormone Receptor Status (HR): Estrogen and progesterone receptors are proteins that are present on the membrane of the tumor cells. Blood hormones (estrogen or progesterone) bind to these proteins creating a sequence of signals that ultimately leads to cell division and thus, tumor growth. Hormone receptor-positive breast cancers have a better prognosis than hormone receptor-negative tumors. In additon, these receptors are a predictive factor for the success of an anti-hormonal therapy. This treatment blocks the stimulating effect of estrogen on cancer cells.
The presence of hormone receptors is determined immuno-histochemically and is expressed as a percentage of positive cells per existing cancer cells (0-100%). The degree of response to anti-hormonal treatment depends on the strength of presence of these receptors. About 60% of breast tumors are hormone receptor-positive.
- Her-2/neu receptor (c-erbB-2 receptor)The HER-2/neu or c-erbB-2 receptor is a protein present in the membrane of the tumor cells. When Growth Factors bind these proteins, a sequence of signals ultimately leads to cell division and thus, tumor growth. Overexpression (overactivity or a high number) of the HER-2 receptor is found in 20-25% of all breast cancers and is usually the result of amplification of the HER-2 oncogene. Overexpression of the HER-2 receptor is correlated with an aggressive cancer and a poor prognosis. It is also a predictive factor for response to a new “target” therapy with an antibody to the receptor, trastuzumab (Herceptin). Treatment with trastuzumab in HER-2 positive patients is useful in advanced stages of breast cancer and as adjuvant treatment. This treatment may decrease the risk of relapse by 50%.
- Lymphatic and vascular invasion: the presence of tumor cells in the lymphatic vessels and blood vessels of the tumor or the presence of affected lymph nodes is a measure of aggressiveness and is a poor prognostic factor.
- Age of patient: young patients often have poorly differentiated tumors with negative hormonal receptor status. Patients younger than 35 years are therefore regarded as high risk.