Introduction

Many patients with hormone-responsive cancer receive endocrine therapy as part of their treatment, often as an adjuvant after surgery, cytotoxic therapy and radiotherapy. However, this treatment often has a lower profile than many of the other therapies and the side effects of endocrine therapy are often overlooked by healthcare professionals and under-reported by patients. One of the reasons for this is because patients receive endocrine therapy as outpatients and have less contact with healthcare professionals. In addition, the toxicities can be ambiguous and patients often don’t know whether they should report the side effect or who they should tell and they are often embarrassed due to the nature of the side effects.

You may meet patients undergoing endocrine therapy in many healthcare settings, whether in the community or an inpatient ward or even a non-cancer placement, as patients may have been taking endocrine therapy for a number of years and may be admitted for another, non-cancer-related reason during that time. It is therefore important that you understand how the treatment works and how patients might be affected in order to provide support and information.

In Chapter 2, we discussed how some cancer cells grow in the presence of hormones (chemical messengers). Using this knowledge, endocrine or hormone therapy is a way of manipulating a patient’s hormones to reduce the growth of a cancer or prevent it from growing back.

Hormones are specific, targeting certain cells in order to act, controlling growth and maturation of organs. The hypothalamus gland is the master, controlling which hormones are produced. It produces a number of hormone releasing hormones that trigger the pituitary gland to release a range of hormones that target certain organs in the body that then produce the hormone end product.

To give an example, the hypothamus produces luteinising hormone-releasing hormone (LHRH), which in turn stimulates the pituitary to release luteinising hormone, which stimulates the ovary to produce oestrogen which then triggers ovulation. Figure 14.1 identifies the hormone pathways particularly significant in cancer.

Fig 14.1 Hormone pathways significant in cancer

Hormone levels are controlled by a process of negative feedback: in a situation where there is too much hormone, there is a signal to the hypothalamus and/or pituitary which inhibits and reduces the hormone production; where there is not enough hormone, a signal to the hypothalamus and/or pituitary increases production. Another way of controlling hormone levels is by increasing the numbers of cell receptors on the cell surface. If there is too much hormone, the number of cell receptors decreases – downregulation – and where there is too little, the number increases – upregulation.

How endocrine treatments work

Cancers that arise from organs normally under hormonal control may be treated by endocrine therapy, namely breast, prostate, thyroid and endometrial cancers. Endocrine therapy either blocks hormones, increases hormones or inhibits the conversion of hormones. Generally, these treatments are not curative, but are useful neoadjuvantly, adjuvantly, palliatively and possibly as a preventative measure. Sometimes endocrine therapy is used as a sole treatment, where other treatments such as surgery are not recommended or a patient wishes to undergo a less invasive treatment. One of the reasons why endocrine therapy does not get rid of cancer completely is because as the cancer mutates, the cells look and behave differently to one another. Often some of the cells will be responsive to endocrine treatment, while others will not be. Sometimes a cancer will respond initially, but may become less responsive as the cancer mutates further. As stated in Chapter 2, at diagnosis a patient is tested to see if the cancer is sensitive to hormones. Sixty-five per cent of women with breast cancer will be oestrogen positive – these tend to be older women and they are more likely to have a better prognosis.

Tamoxifen is probably one of the oldest endocrine therapies. It enters the target cell and binds to a receptor, preventing the normal reaction taking place and slowing/stoping cell division. Fulvestrant works in a similar way by blocking the receptor; it also downregulates the number of cell surface receptors, making the cell less sensitive to the hormone. This drug may be used if a patient is resistant to tamoxifen. Goserelin (Zoladex) is an LHRH given as a subcutaneous injection. Once in the body, the LHRH stimulates the production of luteinising hormone and ultimately oestrogen. This surge of oestrogen triggers the negative feedback and stops production of oestrogen for a number of weeks. This drug is commonly used in premenopausal women. Goserelin has recently been trialled in women with breast cancer having cytotoxic drugs, to stop ovulation in an attempt to preserve fertility.

Remember that oestrogen is not only produced by the ovaries but also by the adipose tissues. After the menopause, a woman will continue to produce oestrogen because aromatase enzymes convert androgens into oestrogen. To stop this, the aromatase inhibitors (such as anastrozole) bind with the enzyme and stop the conversion. These drugs are now recommended by NICE (2006) for postmenopausal women with primary breast disease.

Patients with prostate cancer generally respond well to endocrine therapy. Luteinising hormone-releasing hormone (LHRH) analogues are given adjuvantly after surgery; anti-androgens are often combined and used neoadjuvantly or as a sole treatment. Oestrogens are not used as much for prostate cancer as their side effects are severe and unpleasant.

Table 14.1 summarises the main endocrine therapies

Table 14.1 Types of endocrine drugs

Other ways of manipulating hormones is surgerically (oophorectomy or orchidectomy) or by giving radiation to the ovaries or testes. This is a drastic action as it is permanent and, with the development of the drug therapies, is rarely done. Oestrogen production can also be reduced by using cytotoxic drugs, although this is not the primary aim of chemotherapy. A woman may experience an early menopause, especially if in their late 40s.

Side effects

Many of the endocrine therapies have undesirable effects causing physical discomfort and psychological trauma. The side effects are often under-reported and undiagnosed as the patient has been discharged from hospital and the effects develop gradually and can become chronic. Some of the common toxicities include the following:

Men often experience erectile dysfunction and develop female physical characteristics such as higher pitched voice, breast enlargement and hot sweats. This can be quite distressing and can influence an individual’s sexuality and body image.

Because goserelin (Zoladex) creates a surge in hormone, patients may experience tumour flare, which may temporarily increase pain and hypercalcaemia (if they have bone metastases). Patients need to be aware of this before receiving treatment as the increase in pain can cause considerable physical distress, requiring additional analgesia, as well as anxiety if the increased pain is interpreted as disease progression.

Ending treatment

The end of treatment can be a particularly stressful time for a patient and their family. It is a period of uncertainty – Has the treatment worked? What will happen in the future? Will it come back? Who do I talk to if I have a concern?

Many patients feel lost in transition – they are no longer attending hospital regularly and their GP may not know their case very well. The majority will be followed up as an outpatient and their response to treatment will be reviewed. If the treatment was for symptom management, they may be seen more regularly to monitor the effectiveness of treatment and for additional treatment.

A patient may gauge their body’s response to treatment subjectively and indicate that their symptoms have improved but this is often difficult to measure. For instance, a patient may feel better and their pain may be reduced, however the cancer may have only shrunk a little or not at all.

The next chapters explore some of the symptoms a patient with cancer may experience, and address the possible outcomes of diagnosis, end of life care and living with and beyond cancer, considering the long-term effects a diagnosis might have on an individual and their family.