Although breast cancer can occur in males it is rare, but breast cancer is very common in women. Earlier chapters discussed screening, diagnosis and epidemiology and I now want to explain what choices are available for the management of breast cancer.
Surgery is the first treatment considered when a breast lump is found. There are essentially two treatment choices. Either a mastectomy is performed where all the breast tissue is removed, or only the lump is removed and the rest of the breast is irradiated. The second procedure preserves the breast and large clinical trials have confirmed that the survival outcomes are equivalent. Not every patient is suitable for breast conservation.
A large cancer in a small breast would mean a poor cosmetic result. Reconstruction of the breast then becomes an option. In patients with locally advanced disease with a big primary or fixed lymph glands beneath the arm, chemotherapy and radiotherapy may precede surgery to shrink the disease first.
The other surgical procedure considered is to remove the lymph glands from beneath the arm (axilla). The two reasons for doing this are that it removes any breast cancer that has reached the nodes and it also has significance for deciding how the disease is going to behave and whether additional treatment will be necessary. This latter reason for surgery to the axilla is becoming less important.
Not so long ago, patients with cancerous glands under the arm were offered additional systemic therapy, those without were not. This was based on the fact that the survival of women with positive nodes was shorter than if glands were not involved, and additional treatment had been shown in clinical trials to improve that survival. However, some node-negative women will benefit from additional therapy. It has been difficult to judge who they are.
Some doctors treat all women with adjuvant therapy, others try to pick the node-negative group with the more aggressive disease as evidenced by the size of the primary and various markers on the cell which are demonstrated by the pathologist and correlate with aggressiveness.
There are two types of additional therapy after surgery. Local radiotherapy is given to improve local control and prevent the breast cancer returning locally. Whether it is necessary depends on factors such as the extent of the surgery, the size of the primary, the closeness of the cancer to the surgical margins and the spread to the axillary nodes, which may suggest that other surrounding nodes are involved.
It is more important, however, to prevent distant relapse. We need systemic therapy for that and there are two main choices — hormone treatment and chemotherapy. We want to be aggressive upfront because the disease at this stage can still be cured. We can measure the likelihood of a breast cancer responding to hormone treatment by measuring whether it has receptors for hormones on its surface. Those tumours which are positive for oestrogen and progesterone receptors are more likely to respond to hormone manipulation and have a better outlook. Again, a few years ago, the story was simple.
Women who had gone through the menopause were treated with hormones, while those still menstruating were treated with chemotherapy. There followed a series of clinical trials and an analysis, called a meta-analysis, of all the data collected from multiple trials of adjuvant therapy. Adding chemotherapy to hormone therapy in the postmenopausal group appears to add survival benefit. The same may be seen in the premenopausal group but chemotherapy there also interferes with menstrual cycles, which may explain part of its success.
The options for hormone therapy in the premenopausal group include removing the ovaries or using hormone injections or tablets. Tamoxifen, an anti-oestrogen, is the most common tablet given to postmenopausal women.
There are several choices possible for chemotherapy when used in addition to surgery. Overall, the greatest benefit is in the premenopausal group, where there has been a reduction in deaths by up to 25 per cent by ten years. Conventional-dose chemotherapy regimens, which are the same as those used to treat metastatic disease, fall into those containing an anthra- cycline drug such as doxorubicin and those based on the common regimen CMF (cyclophosphamide, methotrexate and 5 fluorouracil).
Current chemotherapy regimens still do poorly with women who have a large number of lymph glands involved under the arm. This is the group, in particular, where high-dose regimens requiring bone marrow or peripheral blood stem cell transplants have been investigated. Early results have been promising, but only in highly selected groups of patients. There are currently several large randomised trials of high-dose against standard-dose therapy that will tell us the place of this treatment.
For widespread disease, either chemotherapy or hormone therapy is used. Widespread breast cancer is incurable, with an average survival of two years. This is a reason for wanting to put so much effort into initial therapy when the disease is still curable. Controlling metastatic disease, however, is important for quality of life. Hormone therapy, which is simple and has few side effects, is preferred but is only useful if the cancer is hormone receptor positive. Many new hormones are becoming available and several different hormones can be tried against responsive cancers. Hormones take some weeks before their effect is seen.
Rapidly progressive disease or cancer in vital organs such as the liver or lungs should therefore be treated with chemotherapy, and hormone therapy should be left for disease in structural tissues such as the skin, lymph glands or bones. There are several different well defined drug combinations that are very effective in shrinking breast cancer. The good news is that there is also a number of new agents, particularly the taxanes, that are proving very effective against metastatic disease and are being incorporated into standard treatments. High-dose chemotherapy is also being explored in this setting.
Symptom control can also be aided by radiotherapy, which in short courses is very effective in controlling bone pain. A new class of drugs called the bisphosphonates, some of which are now available in tablet form, can also prevent some of the problems associated with having breast cancer in the bones.