Breast cancer and menopausal symptoms
The Pharmaceutical Journal Vol 264 No 7102p968
June 24, 2000 Forum
American Society of Clinical Oncology
Breast cancer and menopausal symptoms
UK cancer trials update
Researchers look at growth factor signalling in search for new targets for anticancer drugs
The management of menopausal symptoms, such as hot flushes, in women with a history of breast cancer is a challenging problem. Many of those developing breast cancer will have already passed through a natural menopause, others will experience a premature cessation of menstruation as a result of cytotoxic chemotherapy and, as Dr Charles Loprinzi on behalf of the Central Cancer Treatment Group (Rochester, US) explained at the recent ASCO meeting in New Orleans, menopausal symptoms can also be exacerbated or triggered by the widely used oestrogen antagonist, tamoxifen.
He added that, although oestrogen and progestogen supplementation was effective in reducing the severity of the hot flushes associated with oestrogen deprivation, breast cancer survivors and their physicians were often reluctant to embark upon hormone therapy because of fears that tumour growth would be stimulated.
Antidepressants and hot flushes
For this reason, Dr Loprinzi's group had conducted a series of trials with non-hormonal agents for the control of hot flushes. Recently their attention had been focused on the newer antidepressants, including venlafaxine. At the ASCO meeting, Dr Loprinzi presented data from a study in which women with a history of breast cancer, but no evidence of active disease, who required treatment for troublesome hot flushes were randomised to receive once daily treatment with a placebo or venlafaxine at a dose of 37.5, 75, or 150mg. There were at least 40 patients in each arm of the study and treatment was continued for four weeks. Efficacy was determined by the use of diaries in which patients recorded both the number and severity of hot flushes. From these a daily "hot flush score" (frequency x severity) was calculated.
Patients in all four treatment arms experienced a subjective improvement in their symptoms, ranging from a 25 per cent reduction in hot flush score for patients on placebo to a 60 per cent reduction for those taking 75mg venlafaxine each day. All three groups of patients receiving the antidepressant fared significantly better than those on placebo. The 75mg venlafaxine dose was significantly more effective than 37.5mg daily, which only reduced hot flush scores by 40 per cent, but no less effective than 150mg.
Although venlafaxine was generally well tolerated, it did cause more nausea, anorexia and mouth dryness than placebo.
Clonidine is another agent that has long been used for the non-hormonal management of hot flushes and its efficacy in this situation has recently been assessed in a placebo controlled, randomised study of similar design to that used by Dr Loprinzi's group. The results of this multicentre study were presented at the ASCO meeting by Dr K. J. Pandya (Rochester, US).
In this investigation, 198 postmenopausal women receiving adjuvant tamoxifen therapy after surgery for breast cancer, and who were experiencing at least one hot flush each day, were randomised to oral treatment with clonidine 0.1mg or placebo, taken at night. Hot flush frequency and quality of life were assessed after four and eight weeks of treatment and compared with measurements made at the start of treatment.
Although both placebo and clonidine treatment reduced the hot flush frequency and improved quality of life, clonidine was significantly more effective in both respects after one and two months of treatment. The only adverse effect significantly more common after clonidine treatment was difficulty in sleeping, reported by 41 per cent of patients compared with 21 per cent of placebo recipients.
Discussing Dr Loprinzi's presentation on venlafaxine, Dr Daniel Hayes (Georgetown, Washington, US) said that, although hormone replacement therapy was the most effective means of dealing with hot flushes - oestrogens being two to five times more active than placebo and progestogens having similar efficacy to oestrogens -there were now a number of other treatments to choose from when hormone replacement was considered undesirable.
Of these, he said, vitamin E and soy products were only marginally better than placebo, with the activity of soy probably a consequence of its phyto-oestrogen content. He added that, although clonidine was demonstrably more active than these "natural" remedies, the most potent treatments currently available appeared to be the newer antidepressants, with fluoxetine, sertraline, paroxetine and venlafaxine all having shown high levels of activity in well conducted clinical trials.
As Dr Hayes explained, the use of antidepressants in this situation was not based on an understanding of the aetiology of flushing, which was poorly understood, but on the chance observation that flushing abated in women receiving these drugs for the treatment of affective disorders.
Use of HRT
Although many clinicians are unhappy to give hormone replacement therapy to women with a history of breast cancer, it is still unclear whether such an intervention increases the risk of cancer recurrence.
A case control study presented in New Orleans by Dr D. A. Decker, on behalf of investigators from the William Beaumont hospital (Royal Oak, Michigan, US) examined the issue. This ongoing investigation has, so far, identified 190 breast cancer survivors receiving oestrogen replacement therapy for menopausal symptoms. These women did not have active disease at the time of study entry, received at least three months of hormone treatment and were followed up for a median of 2.8 years.
Compared with a control group with a similar history of breast cancer and matched for disease stage at diagnosis, age at diagnosis, tumour histology and duration of follow up, but who were not receiving oestrogen therapy, the treated patients showed no significant difference in the number of new primary breast tumours or recurrent tumours they developed or their time to disease relapse.
Although this is encouraging news for women with breast cancer and menopausal symptoms needing oestrogen treatment, it was pointed out during a discussion of Dr Decker's study that the study's small size made it unlikely that it would have uncovered any small increase in breast cancer risk associated with HRT.
Dr Summerhayes is principal oncology pharmacist,Guy's and St Thomas's hospitals NHS trust. He attended the ASCO meeting as a guest of Roche Products
Citation: The Pharmaceutical Journal URI: 20001941