In the last few months there have been a number of media releases about new drugs effective in breast cancers that express estrogen receptors. But what of estrogen receptor negative disease? What is new in this area? And are there any new treatments that women and health care providers should be made aware of?
What are estrogen receptors? Years ago, doctors noticed that some breast cancers respond to estrogens and others do not. The cancers that do respond have receptors on the cell that are stimulated by hormones; this stimulation causes growth and division of the cancer cells. Breast cancers have receptors to two female hormones, "estrogen" and "progesterone." These receptors can be measured in the laboratory and are part of a standard pathology report. Approximately 70% of breast cancers are estrogen positive. This percentage is highest in older women and lower in young women but a woman of any age may have an estrogen receptor negative tumour.
Breast cancers can be estrogen positive and progesterone positive (ER+PR+), ER+ and progesterone negative (ER+PR-), ER-and PR- or very, very rarely ER-PR+. There are various levels of positivity with 3+ having the highest level of estrogen receptors. Progesterone receptors are thought to be important in helping the estrogen receptor function.
Hormone receptor status gives us information about how the cancer will behave (prognostic factor) and how it will respond to treatment (predictive factor). Only hormone receptor positive cancers respond well to the common hormone treatments that we have. Studies show that a tumour with the highest level of estrogen receptors may respond better to hormone therapies than one that has a lower reading but any positive level may be associated with a response.
Studies suggest that ER-negative tumours may respond better to chemotherapy than ER-positive tumours. This has been shown in an analysis of a large number of studies and was true for women of all ages. More recent studies confirm this. This does not suggest that chemotherapy is not effective in estrogen receptor positive tumours but simply that tumours that are estrogen receptor negative may have a better response. This is reassuring to women who have estrogen negative tumours where the only option is chemotherapy as hormonal therapy is not effective. There are, however, no specific chemotherapy drugs or protocols that should be used in estrogen receptor negative tumours.
In early stage breast cancer, it appears that estrogen receptor status may also be a prognostic factor; this means that it tells us something about how the cancers will behave. Large analyses of women with early breast cancer, who did not receive any therapy after surgery, reported estrogen receptor positive tumours recurred slightly less frequently than estrogen receptor negative tumours in the first five years. This was a difference of only 5 - 8%. However, with follow-up continuing after five years this advantage disappeared and at 8 -10 years after diagnosis, both types of tumours were found to relapse at the same rate.
|
One of the challenges is to discover new drugs that will be effective in estrogen receptor negative tumours which may be better tolerated and may further decrease the risk of recurrence. This requires studying tumours to understand the molecular or genetic engines that drive the growth of a tumour. In estrogen receptor positive tumours this may be estrogen.
In the 20% of breast cancers with too much HER2, this gene may be the major engine causing growth. However, for most estrogen receptor negative tumours we do not know what the molecular engines are. In some estrogen negative tumours, it may be a member of the HER family, HER1 which is also known as EGFR (epidermal growth factor). HER1 is not as easy to measure as HER2 as cells do not simply have too much HER1. Researchers are discovering that HER1 may function abnormally or cause other molecular factors to function abnormally. This is an area of active research and at this time, it is not clear how important HER1 may be. Studies are ongoing of drugs that target HER1 and the whole HER family (HER1, 2, 3 and 4) at once. Other molecular or genetic abnormalities are also being studied to determine if they are important in cell growth. These include p53, PTEN, IGFR, mTOR and others, none of which are measured routinely in clinical labs. We do not yet know their significance, but this work is exciting.
In the future molecular markers will be measured for each breast tumour. Drugs are being developed that target these factors. And tumours that are estrogen receptor negative will be treated with a mixture of chemotherapy and new targeted drugs, if they are shown to be beneficial. With these advances, hopefully treatments will be more effective, leading to more cures. With all the new research there will be more options for treating both estrogen receptor negative and positive tumours.
|
