Psychosocial support, treatment of metastatic disease and palliative care

This article deals with four linked but distinct aspects of care for women with breast cancer, with an emphasis on the pivotal role of the general practitioner:

1. Modern medicine is fast recognising the need for psychosocial support of patients; in fact, for an integrated approach to caring for the whole person at all stages of illness.

2. Oncological treatment of metastatic disease needs to be individualised and based on realistic expectations of outcome balanced against side effects.

3. An open dialogue about the role and appropriateness of so-called "alternative" or "complementary" therapies is needed.

4. Despite significant improvements in palliative care quality and access in Australia in the last decade, many practitioners still require support and advice in this demanding area of care (particularly about difficult symptom control).

Psychosocial morbidity can extend throughout the family. It has been shown that for those women who enter palliative care programs, substantial psychological morbidity is identifiable in half the patients, a third of spouses and a quarter of their offspring.¹⁰ Family-centred care that recognises family members not only as primary care providers but also as second-order patients is essential.⁷ There is a clear role for general practitioners in this process, as an integral part of good family medicine practice.

The themes which need to be addressed are summarised in Box 2. Therapeutic interventions should be appropriate to the stage of the disease and the woman's personal situation (Box 3). Good clinical care requires that medical, surgical and nursing staff provide opportunities for patients to express their concerns, anxieties and preoccupations throughout routine management.

Coping skills and cognitive behaviour therapies¹¹ may be more applicable to early stage disease, while supportive psychotherapies which encourage the sharing of feelings about existential concerns are more suited to patients with metastatic cancer.¹² Another approach utilises the central concept of loss. Women with breast cancer grapple with many losses -- their health, breast, sense of femininity, confidence, dreams and belief in the future. A primary goal, therefore, is to facilitate adaptive grieving. So-called grief therapy¹³ can be pivotal in much cancer counselling, particularly in the light of the pervasive pressure on women "to think positively". It is also important to deal with the possibility of death. Education and clarification of fears can help promote a sense of realism-based mastery.

Group therapies are cost-effective, provide a supportive network and are acceptable to about two-thirds of women.

Pharmacological treatments complement psychotherapeutic approaches (see Box 4). Major tranquillisers and benzodiazepines can allay anxiety, assist in crises and help to contain distressing features of delirium. Tricyclic antidepressants and selective serotonin reuptake inhibitors help in depressive disorders. They are prescribed for major depression, when sleep disturbance or other depressive symptoms are moderate in degree and when poor coping and chronic grief are persisting.

Reduced sex drive² and reduced frequency of intercourse invariably follow the initial diagnosis. Open communication about intimacy and sexuality is desirable and may need to be initiated by clinicians. The general practitioner should be approachable for first contact on these issues. Clarification of the role of altered body image, grief, depression, the nature of the relationship and adjustment of both partners is necessary before endocrine assessment is considered.

Although at present psychological interventions are usually offered only to those who have become symptomatic or are perceived to be particularly at risk, recent studies suggesting an association between psychological wellbeing and survival compel us to consider whether such therapies should be offered routinely.^12,14,15 The experience of stressful life-events, loss of hope, helplessness, social isolation and failure to share negative emotions have all been associated with poorer outcome.¹⁶ Large multicentre replication studies of group therapy for women with both early stage and metastatic breast cancer are currently proceeding in the United States, Canada and Australia, in the hope of clarifying how critical this role of support and coping is to overall survival.

Endocrine therapy: For premenopausal patients ovarian ablation (by oophorectomy or radiation) may be replaced by medical treatment with the luteinising hormone-releasing hormone agonists (e.g., goserelin and leuprorelin acetate). For postmenopausal women the antioestrogen tamoxifen and oral progestogens (medroxyprogesterone acetate and megestrol acetate) are the most commonly prescribed treatments. Aromatase inhibitors (e.g., aminoglutethimide and formestane [4-hydroxy androstenedione]) have replaced adrenalectomy for those postmenopausal patients who have exhibited protracted responses to initial endocrine treatment.

Chemotherapy: The initial high response rate of metastatic breast cancer to cytotoxic drugs and the eventual development of resistance raise several important issues in management. Combinations of cytotoxic drugs offer a better chance of response than single agents, but do not yield substantially better survival for most patients. The exception is those patients with life threatening visceral metastases (normally in liver and lung). Regimens including anthracyclines (doxorubicin, epirubicin) are the most effective and are useful for aggressive or life threatening disease. Less aggressive disease may be treated with less toxic regimens, frequently based on mitozantrone, although there are a considerable number of alternative options. Second and even third line regimens are indicated when disease progresses after an initial response, but response rate and duration are usually less with each subsequent regimen. All treatments must be presented to patients as a balance between a potentially beneficial tumour response and unwanted cytotoxic effects.

Studies of dose intensification of cytotoxic drugs suggest higher rates of response but only a minor improvement in survival. The logical extension of these observations is the application of very high doses of cytotoxic drugs followed by bone marrow rescue, in an attempt to achieve maximum tumour control. Initial results indicate high rates of response, but the ultimate worth of these treatments awaits further evaluation and their use should be confined to assessment in randomised controlled trials. Alternative approaches include constant infusional chemotherapy, such as fluorouracil given over many weeks, often with low toxicity. Newer agents such as taxol have been extensively researched and are likely to be approved for second or third line treatments.

The sensitivity of metastatic breast cancer to both cytotoxic and hormonal treatments and their different mechanisms of action make combined treatments attractive. However, the results of a trial comparing sequential and concurrent administration of tamoxifen and cytotoxic drugs (doxorubicin and cyclophosphamide) failed to demonstrate better survival with combined modality treatment.¹⁷ One Australian study comparing standard (continuous) and less intensive (intermittent course) cytotoxic drug treatment showed that the control of symptoms and quality of life were superior in the group receiving continuous chemotherapy, with a longer time to progression of cancer and better survival in this group.¹⁸ A follow-up study evaluating the physician's assessment of quality of life showed that those patients assessed as having better quality of life at the time of entry into the study also had better survival.¹⁹ It remains to be determined at what point dose intensity and better survival in metastatic breast cancer will be offset by unacceptable quality of life, and the study should not be interpreted as justifying the routine use of chemotherapy for advanced disease in the absence of defined symptoms. It is also possible that the patients receiving the more intensive treatment believed (despite information to the contrary) that they had a better chance of cure or remission. Patients' beliefs about treatment goals certainly require more research and understanding, for both standard and alternative therapies.

Radiotherapy: Radiotherapy plays a major part in the palliation of a variety of localised symptoms. Box 6 lists the role of palliative radiotherapy, which can generally be given in one to five (daily) fractions, frequently on an outpatient basis, with the reasonable expectation of a significant impact on symptom control for most patients. A randomised study of bone pain palliation has confirmed that short courses are as effective and non-toxic as longer courses of two weeks or more.²⁰

The need for patients to participate in decisions about treatment should be emphasised at all times. Doctors should recognise the limitations of modern oncological treatment, and be prepared to acknowledge the patient's need to explore other avenues. It is often helpful for doctors to offer to comment on this issue and such an offer is rarely rejected. There may be times when doctors feel that they must advise patients of a dangerous or futile treatment, with the occasional possibility of real harm being caused, and it should be pointed out that many therapies are completely untested.

Sometimes it is helpful to differentiate between therapies which patients believe might cure them and those that help them to live more comfortably with their disease. Gentle exploration of patients' beliefs about potential curability of their disease may be important. Positive thinking strategies which obstruct appropriate care delivery for a dying patient may also need skilful addressing.

Active oncological intervention is often required for malignant bone pain, fungating chest-wall disease or liver, lung or brain metastases, and can be of value until a very late stage in the disease process. About 10% of patients with metastatic breast cancer will develop symptomatic hypercalcaemia (symptoms include nausea, vomiting, polyuria, drowsiness) and should be treated with intravenous rehydration, diuretics and a bisphosphonate infusion. Pleural effusions may require aspiration if symptomatic. If they recur, pleurodesis with talc, tetracycline or BCG may be required for control of breathlessness. Meningitic carcinomatosis is very rare and may respond to intrathecal cytotoxic agents or craniospinal irradiation.

It is important that the general practitioner be fully informed of the patient's management and condition. During a long disease course, often with multiple oncological events, it is all too easy (and understandable) for patients and families to become attached to a hospital oncology service and its staff. This may pose problems for palliative and terminal care at home, as a hitherto relatively uninvolved general practitioner may have to suddenly take over care.

See Box 7 for definition of palliative care.

Early referral to a specialised palliative care source should be considered for most patients with metastatic disease, to introduce future options in palliative care. Although sometimes confronting for patients and their oncological caring team, a commitment of future support and proper care planning is of real value in allowing patients to plan to live until they die. The general practitioner should be actively involved in this process of communication to ensure the smoothest possible transitions from curative to palliative and terminal care.

In psychosocial support, emphasis is often required on issues of family history (anxieties about daughters developing the disease), body image and loss of femininity, although concerns about the latter may be less pronounced than at initial diagnosis. For younger women with children, death will leave the children without a mother, which is probably the hardest aspect for a woman to bear. Work on helping to hand over present and future parenting roles is required.

The proper and appropriate use of opioid drugs is an essential skill for control of pain and shortness of breath. Nearly 30 years of safe international clinical experience has led the World Health Organization to recommend morphine as the opioid of first choice in cancer pain management.²³ Other drugs (either alone or in combination with morphine) are usually required for deep somatic pain caused by bone metastases or liver capsule inflammation (non-steroidal anti-inflammatory drugs and corticosteroids), and neurogenic pain (antidepressants, anticonvulsants, membrane stabilising agents). Specialist help is nearly always required for neurogenic pain, often with the additional involvement of an anaesthetist with a special interest in cancer pain management.

The regular oral administration of the right dose of an appropriate drug or drug combination is the cornerstone of modern cancer pain management. The dose of morphine is adjusted according to the patient's top-up (or "breakthrough") requirements. The management of cancer pain with morphine is somewhat unusual in that there is no absolute upper dose limit. Most patients will achieve initial pain control on an oral 24-hour morphine dose in the range of 100-200 mg, but there is very wide individual variation and if the dose continues to rise without response the cause of the pain and the drug choice should be reassessed.

Advice about anticipated side effects and their prompt and effective management is essential, together with frequent review of pain control and analgesic dose. Intermittent subcutaneous injections or infusions may be used if the oral route is not possible (e.g., because of nausea and vomiting), or not effective.

Shortness of breath, anxiety, acute delirium and so-called terminal restlessness may be managed with anxiolytic drugs such as diazepam, midazolam or clonazepam (after looking for a specific treatable underlying cause). Antiemetics also require regular administration in adequate doses, and may need to be used in combination (e.g., prochlorperazine 25 mg rectally 3-4 times daily with metoclopramide 30-90 mg per 24 hours by subcutaneous infusion). Bowel care is important (and often neglected) throughout the illness, but particularly towards the end of life. Most patients taking morphine will require a regular prophylactic aperient. Intensification of supports and symptomatic treatment will usually be required as death approaches, particularly if the patient and family have chosen for this to occur at home with the help of a domiciliary palliative care team (Box 8).

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Department of Psychiatry, Monash Medical Centre, Clayton, VIC.
David W Kissane, FRACGP, FRANZCP, Senior Staff Specialist, and Senior Lecturer, Department of Psychological Medicine, Monash University.

Wesley Medical Centre, Auchenflower, QLD.
Geoffrey F Beadle, FRACP, FRACR, Medical Oncologist.

William Buckland Radiotherapy Centre, The Alfred Health Care Group, Alfred Hospital, Prahran, VIC.
Alan Rodger, FRCS, FRACR, Director and Professor, Department of Radiation Oncology, Monash University.

No reprints will be available.
Correspondence: Professor M A Ashby, McCulloch House, Monash Medical Centre, Clayton, Vic 3168.