Stage, Grade and Receptors: What are they?
Stage
Many patients ask what their “stage” is. My advice is not to get hung up on these medical terms. They are mainly useful in working out the best treatment for different categories of patients. I have known plenty of women with Stage III and even Stage IV cancer who are doing fine many years later. However, for the record:
There are four stages of breast cancer:
Grade
The “grade” of a breast cancer refers to its appearance down the microscope. The pathologist looks at the shape and characteristics of the cancer cells and “grades” them against well-defined criteria to decide whether they fall into one of three grades:
DO NOT WORRY IF YOUR TUMOUR IS GRADE 3! Most young women have Grade 3 tumours and I know countless women who have had Grade 3 tumours over 15 years ago and have never had further problems. Grade 3 tumours may be more sensitive to treatments like chemotherapy and radiotherapy, so from that perspective it can even be an advantage to have a grade 3 tumour.
Receptors
Breast cancer cells have tiny ‘docking stations” on their surface which allow certain hormones to dock and send signals to the cell to grow. The most important of these are the hormone receptors: the oestrogen receptor (spelt “estrogen” by the Americans, and therefore universally abbreviated as “ER”) and the progesterone receptor (PR).
When these receptors are present they indicate that it is advisable to deprive the cancer cell of the female hormone, oestrogen, to ensure that the cancer cells don’t grow. There are several ways of doing this and you can read more about it if you click here.
What if my hormone receptors are “negative”?
Tumours that do not express the oestrogen and progesterone receptor are termed hormone receptor negative. For women with receptor negative tumours the presence of circulating female hormones, like oestrogen, are far less relevant. Hormone therapy is not used when the hormone receptors are negative as it has no beneficial effect.
DO NOT WORRY IF YOUR TUMOUR IS RECEPTOR NEGATIVE! Receptor negative tumours may, in fact be more sensitive to other treatments, like chemotherapy, than receptor-positive tumours, so, from this perspective, it may even be an advantage to have a receptor-negative tumour.
Many patients ask what their “stage” is. My advice is not to get hung up on these medical terms. They are mainly useful in working out the best treatment for different categories of patients. I have known plenty of women with Stage III and even Stage IV cancer who are doing fine many years later. However, for the record:
There are four stages of breast cancer:
- Stage I: The tumour is confined to the breast
- Stage II: The tumour is confined to the breast, but is larger than 2 cm in diameter, or involves the local lymph nodes, usually those in the arm pit, or “axilla”.
- Stage III: As for Stage II, but more advanced. The tumour is extending to other local structures, but has not spread to distant sites.
- Stage IV: The tumour has spread to distant organs, like bone, lung or liver.
Grade
The “grade” of a breast cancer refers to its appearance down the microscope. The pathologist looks at the shape and characteristics of the cancer cells and “grades” them against well-defined criteria to decide whether they fall into one of three grades:
- Grade 1: These are slow-growing, quieter cancer cells.
- Grade 2: Intermediate
- Grade 3: These are faster growing cancer cells
DO NOT WORRY IF YOUR TUMOUR IS GRADE 3! Most young women have Grade 3 tumours and I know countless women who have had Grade 3 tumours over 15 years ago and have never had further problems. Grade 3 tumours may be more sensitive to treatments like chemotherapy and radiotherapy, so from that perspective it can even be an advantage to have a grade 3 tumour.
Receptors
Breast cancer cells have tiny ‘docking stations” on their surface which allow certain hormones to dock and send signals to the cell to grow. The most important of these are the hormone receptors: the oestrogen receptor (spelt “estrogen” by the Americans, and therefore universally abbreviated as “ER”) and the progesterone receptor (PR).
When these receptors are present they indicate that it is advisable to deprive the cancer cell of the female hormone, oestrogen, to ensure that the cancer cells don’t grow. There are several ways of doing this and you can read more about it if you click here.
What if my hormone receptors are “negative”?
Tumours that do not express the oestrogen and progesterone receptor are termed hormone receptor negative. For women with receptor negative tumours the presence of circulating female hormones, like oestrogen, are far less relevant. Hormone therapy is not used when the hormone receptors are negative as it has no beneficial effect.
DO NOT WORRY IF YOUR TUMOUR IS RECEPTOR NEGATIVE! Receptor negative tumours may, in fact be more sensitive to other treatments, like chemotherapy, than receptor-positive tumours, so, from this perspective, it may even be an advantage to have a receptor-negative tumour.
Nicole: |
The HER2 receptor and Herceptin.
This warrants its own page. Click here.
Molecular forecasting to predict breast cancer treatment
Patients often ask me how we know that adjuvant chemotherapy or hormone therapy is going to be successful for them. At present, we do not have a reliable way of individualising the decision about adjuvant treatment. We have to base it on the fact that in large clinical trials the group of women who had adjuvant treatment do much better over time than the group of women who did not have such treatment. Within that group, however, there may be as many as two-thirds who do not need the treatment.
In recent times, molecular profiling tests have become available although they are not reimbursed by the government and come at a cost of between $2900 and $4500 depending on which test is used. The technology involves taking the tumour and preparing a genetic fingerprint. This fingerprint is compared to the fingerprint of tumours that are known to be sensitive to chemotherapy, or hormone therapy, and also compared with the fingerprint of tumours that are known to be resistant. In this way, it is possible to select patients who are going to have maximum benefit from the treatment.
There has been a recent review of these kinds of tests. The guidelines recommend that they only are used in a certain subset of patients - those who have tumours which have "mixed" features, for example a patient who has a tumour which is Grade 2 but has some aggressive features which are not usually found with similar types of grade 2 tumours. For most cases, it is often a straight forward decision regarding who needs chemotherapy and who does not. It is only in the cases where we are "not quite sure" that these molecular profiling tests should be considered. Molecular profiling is not recommended for people who have HER2 positive or hormone receptor negative disease.
The two tests that I use most and therefore know the most about are Oncotype Dx and Endopredict.
Oncotype Dx tests a panel of 21 genes and is designed to establish which tumours will have a better response to chemotherapy. Whilst is well validated, it costs $4500 and it takes approximately 3-4 weeks to get a result. The other negative is that often the result indicates that a patient's tumour is in the intermediate group. What this means is that the test is not able to determine whether or not the tumour would respond to chemotherapy - so ultimately the clinician needs to make a decision anyway.
Endopredict tests a panel of 11 genes which are associated with a higher risk of recurrence. It is designed to determine an individual's risk of developing of distant (metastatic) disease within a 10 year period with endocrine therapy alone. Whilst this doesn't determine if chemotherapy will be effective, it transpires that if a person is at a high risk of developing distant disease, then they should perhaps more strongly consider having chemotherapy now. Endopredict testing is done locally in Australia and the turnaround time is approximately two weeks. It currently costs $2980.
Regardless of the costs, if your tumour falls into the category where we should consider this kind of testing, either your surgeon or we will discuss it with you. Do not feel you have to do the test, it is just an option. At the end of the day if you would be more reassured having chemotherapy, then just do it. Save your money.
This warrants its own page. Click here.
Molecular forecasting to predict breast cancer treatment
Patients often ask me how we know that adjuvant chemotherapy or hormone therapy is going to be successful for them. At present, we do not have a reliable way of individualising the decision about adjuvant treatment. We have to base it on the fact that in large clinical trials the group of women who had adjuvant treatment do much better over time than the group of women who did not have such treatment. Within that group, however, there may be as many as two-thirds who do not need the treatment.
In recent times, molecular profiling tests have become available although they are not reimbursed by the government and come at a cost of between $2900 and $4500 depending on which test is used. The technology involves taking the tumour and preparing a genetic fingerprint. This fingerprint is compared to the fingerprint of tumours that are known to be sensitive to chemotherapy, or hormone therapy, and also compared with the fingerprint of tumours that are known to be resistant. In this way, it is possible to select patients who are going to have maximum benefit from the treatment.
There has been a recent review of these kinds of tests. The guidelines recommend that they only are used in a certain subset of patients - those who have tumours which have "mixed" features, for example a patient who has a tumour which is Grade 2 but has some aggressive features which are not usually found with similar types of grade 2 tumours. For most cases, it is often a straight forward decision regarding who needs chemotherapy and who does not. It is only in the cases where we are "not quite sure" that these molecular profiling tests should be considered. Molecular profiling is not recommended for people who have HER2 positive or hormone receptor negative disease.
The two tests that I use most and therefore know the most about are Oncotype Dx and Endopredict.
Oncotype Dx tests a panel of 21 genes and is designed to establish which tumours will have a better response to chemotherapy. Whilst is well validated, it costs $4500 and it takes approximately 3-4 weeks to get a result. The other negative is that often the result indicates that a patient's tumour is in the intermediate group. What this means is that the test is not able to determine whether or not the tumour would respond to chemotherapy - so ultimately the clinician needs to make a decision anyway.
Endopredict tests a panel of 11 genes which are associated with a higher risk of recurrence. It is designed to determine an individual's risk of developing of distant (metastatic) disease within a 10 year period with endocrine therapy alone. Whilst this doesn't determine if chemotherapy will be effective, it transpires that if a person is at a high risk of developing distant disease, then they should perhaps more strongly consider having chemotherapy now. Endopredict testing is done locally in Australia and the turnaround time is approximately two weeks. It currently costs $2980.
Regardless of the costs, if your tumour falls into the category where we should consider this kind of testing, either your surgeon or we will discuss it with you. Do not feel you have to do the test, it is just an option. At the end of the day if you would be more reassured having chemotherapy, then just do it. Save your money.