Effects of stellate-ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot study

Summary

Background

Debilitating hot flushes and sleep dysfunction often affect survivors of breast cancer, most notably in those taking anti-oestrogen medications. Conventional treatments have been only partially effective in diminishing these issues, and some have serious risks. We did a pilot study to investigate our hypothesis that stellate-ganglion block can be a safe and effective treatment for hot flushes and sleep dysfunction in this patient population.

Methods

13 survivors of breast cancer (in remission) with severe hot flushes and night awakenings were treated with stellate-ganglion block at the anterolateral aspect of the C6 vertebra on the right side under fluoroscopy. Patients recorded hot flushes in a daily diary by use of the Hot-Flash Score, devised by Sloan and colleagues, and night awakenings by use of the Pittsburgh Sleep Quality Index. Both instruments were used 1 week before the procedure [A40] and then weekly after the procedure for 12 weeks. We used the generalised-estimating-equations method to analyse the longitudinal measurements of the number of hot flushes and night awakenings over time. This method is a popular approach to analysing datasets that have repeated measures from the same person, and is robust because it does not need the complete distribution of the outcomes to be specified. This trial is registered on the International Standard Randomised Controlled Trial Number register (ISRCTN14318565).

Findings

There were no adverse events resulting from the stellate-ganglion block, although patients had temporary Horner's syndrome indicating the effectiveness of the block. Five patients had only one stellate-ganglion block and eight had two stellate-ganglion blocks. The total number of hot flushes decreased from a mean of 79·4 (SD 37·4) per week before the procedure to a mean of 49·9 (SD 39·9) per week during the first 2 weeks after the procedure (p=0·0002). The total number of hot flushes continued to decrease over the remaining follow-up period (weeks 3–12), and stabilised at a mean of 8·1 (SD 5·6) per week (p<0·0001). The number of very severe hot flushes was decreased to near zero by the end of the follow-up period (week 12; p<0·0001). Night awakenings decreased from a mean of 19·5 (SD 14·8) per week before the procedure to a mean of 7·3 (SD 7·1) per week during the first 2 weeks after the procedure (p<0·0001). The total number of night awakenings continued to decrease over the remaining follow-up period (weeks 3–12) and stabilised at a mean of 1·4 (SD 1·2) per week (p<0·0001).

Interpretation

The findings of this study suggest that stellate-ganglion block can provide survivors of breast cancer with relief from hot flushes and sleep dysfunction with few or no side-effects. Long-term relief of symptoms has the potential to improve overall quality of life and increase compliance with anti-oestrogen medications for breast cancer.

Funding

This study was self funded by the primary authors (EGL and JRJ). There were no additional sponsors for this study.

Introduction

Hot flushes are one of the most common symptoms associated with menopause, reportedly occurring in 68–82% of women undergoing natural menopause.¹ Surgical menopause is associated with an increased incidence and severity of hot flushes compared with natural menopause.² Carpenter and colleagues³ report that women who have survived breast cancer have hot flushes that are “significantly more frequent, severe, distressing, and of greater duration” than in other women. These researchers also note that several unique factors, such as ovarian disruption caused by chemotherapy and subsequent early and artificial menopause, might mean that generalisations about healthy women with hot flushes cannot be applied to survivors of breast cancer.

Hot flushes can have a substantial effect on daily living, by disrupting sleep and causing fatigue and irritability during the day.⁴ Severe hot flushes, which can cause rapid heartbeat, diaphoresis, nausea, dizziness, anxiety, headache, and weakness, also substantially increase the risk of sleep deprivation, depression, sexual dysfunction, and other serious medical conditions.

Hot flushes are a frequent and serious side-effect of pharmacological treatments for breast cancer, including oestrogen-synthesis inhibitors, oestrogen antagonists, and aromatase inhibitors. In survivors of breast cancer taking anti-oestrogen medications, hot flushes can even contribute to cancer recurrence by discouraging compliance with treatment regimens. Data show that more than 50% of such patients might be non-compliant after 180 days from initiation of anti-oestrogen treatment.⁵ Poor adherence to medication regimens in patients with breast cancer is a serious issue, because these treatments have a major role in decreasing the recurrence of disease.⁵

In the past, many physicians might have under-rated the severity of hot flushes that result from anti-oestrogen medications and the negative effects of severe hot flushes on patients' lives and health. Although the scale of this issue after breast-cancer treatment is probably still underestimated, hot flushes are beginning to receive attention from health-care professionals.⁶

Current treatment options for hot flushes have varying degrees of effectiveness. Available options include: hormone treatment; herbal remedies; and non-hormonal pharmaceuticals.

Hot flushes are the most common reason for women to seek hormone treatment,⁷ and this treatment option can be effective. However, hormone treatment has substantial complications, including headache, nausea, water retention, premenstrual irritability, and vaginal bleeding, which have a deleterious effect on quality of life.⁸ Withdrawal bleeding is the most common reason for why women discontinue hormone treatment.⁹ Moreover, for survivors of breast cancer, hormone treatment is generally considered contraindicated. A study published in 2004¹⁰ showed a substantial increase in new breast-cancer events in survivors of breast cancer on hormone treatment, leading to early termination of the study because of “unacceptable risk”. Consequently, survivors of breast cancer use hormone treatment much less frequently (fewer than 5% of survivors of breast cancer are on hormone treatment) than women who have not had breast cancer.¹⁰ Use of this treatment option in patients with breast cancer has also decreased noticeably since the Women's Health Initiative reported conflicting and disturbing findings regarding its efficacy and side-effects in survivors of breast cancer.¹¹

For herbal remedies, data suggest that these and lifestyle interventions are, at best, only slightly more effective than placebo.4, 8, 12, 13 Specifically, reviews of non-hormonal treatments for hot flushes concluded that phyto-oestrogens¹⁴ and black cohosh,15, 16 are both ineffective in providing symptomatic relief.

The most promising non-hormonal pharmaceutical treatments include selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), and gabapentin. These drugs have been reported to decrease hot-flush scores. However, SSRIs seem to be much less effective than hormone treatment.¹³ Venlafaxine, an SNRI, can lead to rapid development of anasarca¹⁷ and possible Q–T extension with a possible increase in sudden death.¹⁸ Gabapentin has been reported to decrease hot flushes, but has been associated with a higher risk of suicide¹⁹ and with weight gain,²⁰ compared with placebo.

Another possible treatment for debilitating hot flushes is stellate-ganglion block, used as a means of interrupting parts of the sympathetic nervous system involved in temperature regulation. This procedure might also help treat sleep dysfunction, which is often reported by menopausal women, including survivors of breast cancer on anti-oestrogen medications.

Stellate-ganglion blocks have been done safely for more than 60 years.²¹ We suggest that a properly done stellate-ganglion block might be a safer and more effective treatment for hot flushes and sleep dysfunction in survivors of breast cancer than current pharmacological alternatives. To investigate this hypothesis, we did a pilot study to assess the safety and efficacy of this procedure in a group of survivors of breast cancer. To our knowledge, there have been no previous reports investigating the potential benefits of stellate-ganglion block for hot flushes and night awakening in this patient population. Our previously published anecdotal research on this procedure in 2005 reports a significant decrease of hot flushes in six patients without breast cancer.²² The current study includes survivors of breast cancer.