Cancer and Society

Commonly used treatments for breast cancer are known to induce premature menopause. These include chemotherapy and endocrine (hormone) therapy such as tamoxifen. Such treatments cause suppression of ovarian function. In post-menopausal women, the use of other hormonal drugs—eg, aromatase inhibitors— leads to decreased circulating oestrogen concentrations, that can, in turn, also induce menopausal symptoms, including hot flashes, vaginal dryness, night sweats, depression, fatigue, and altered sexual function. These symptoms tend to be most pronounced in younger women, although they have been reported in patients of any age. To counteract these effects, hormone-replacement therapy or complementary therapies have been used, but there are concerns that in healthy menopausal women hormone-replacement therapy increases the risk of breast cancer. Clinical studies assessing the changing risk of breast cancer with the use of hormone-replacement therapy, including combined preparations of oestrogen and progesterone (for example, the Women’s Health initiative study), showed increased risk of developing breast cancer with hormone-replacement therapy compared with placebo. Another study (the Million Women Study) confirmed this finding and noted that users of hormone-replacement therapy were more likely to develop breast cancer than those who had never used it, with a relative risk of 1·66, and more likely to die from breast cancer, thus use of hormonereplacement therapy in patients already treated for breast cancer has remained controversial. Two further trials done in Sweden also examined whether there was an increased risk of breast cancer recurrence when women who had been diagnosed Vol 16 February 2015

with early breast cancer were treated with horomone-replacement therapy: one study (the HABITS trial) was terminated early because of increased evidence of breast cancer recurrence (relative hazard 3·3) in patients treated with hormone-replacement therapy, whereas the other (the Stockholm trial) contradicted these data and reported no increased risk. Although both studies were designed similarly, the Stockholm trial minimised the use of progesterone combined with oestrogen, which is the normal preparation for hormonereplacement therapy. However, because of the perceived increased risk, oestrogen-based therapies such as hormone-replacement therapy are not generally considered to alleviate menopausal symptoms in patients with a previous history of breast cancer. Black cohosh (Cimicifuga racemosa or Actaea racemosa) is a tall-stemmed plant with white flowers that has been frequently used to relieve menopausal symptoms. The plant is native to Canada and the eastern USA, and was traditionally used by Native Americans to treat a range of conditions including menopause, premenstrual discomfort, menstrual irregularities, malaria, sore throats, and impaired kidney function. More recently, black cohosh extract including the rhizome (underground stem) or roots of the plant have been used in studies to investigate its specific effect on menopausal symptoms. According to 2004 data from the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, 9 million days worth of treatment are purchased per year as single herb tablets and capsules. 27 products, including non-homoeopathic products, containing black cohosh are licensed in the UK. The mechanism of action of black cohosh is not fully understood.

Michael P Gadomski/Science Photo Library

Quackery Black cohosh, hot flushes, and breast cancer

Black cohosh

Initially the product was thought to have oestrogen-like action, but now increasing evidence suggests that this is not the case. Another suggested method of action is via inhibition of serotonin receptors. Mild adverse events can include headaches, vomiting, and gastrointestinal irritation. Liver toxicity is recognised, but the mechanism by which this toxicity occurs in not known; as such, licensed and unlicensed products containing black cohosh have been recommended by the MHRA to hold appropriate warnings. Few studies suggest that liver toxicity reactions occur after roughly 3 months of use. Black cohosh is not currently recommended for use for longer than 6 months. A systematic review of the efficacy of black cohosh for menopausal

See Online for appendix


Cancer and Society

symptoms in healthy women has been published. This comprehensive assessment included 16 randomised controlled trials recruiting a total of 2027 post-menopausal women, and at least five oral preparations of black cohosh. Comparisons in the trials were made to placebo, hormone therapy, red clover (another herbal preparation), and fluoxetine (an antidepressant drug). Compared with placebo, black cohosh showed no difference in changing the frequency of hot flushes, but was significantly less effective at reducing the frequency of hot flushes compared with hormone therapy. Comparisons of red clover and fluoxetine to black cohosh were inconclusive. Although the trials assessed some menopausal symptoms such as hot flushes and vaginal symptoms, they did not elaborate on other factors such as quality of life, bone health, or night sweats. Important aspects such as the safety of black cohosh and cost-effectiveness were not fully evaluated. Based on these data, the evidence for treating healthy menopausal women with black cohosh remains inconclusive. In women with a previous history of breast cancer, few clinical studies have

been undertaken to fully understand the use and safety of black cohosh. Because of the controversy surrounding use of hormonereplacement therapy, the optimum method to evaluate black cohosh is to compare its effect with placebo. In 2001, a randomised controlled trial compared black cohosh with placebo with or without the addition of tamoxifen in women with a previous history of breast cancer. Although no difference in frequency of hot flushes was noted between the treatment groups, the group given black cohosh had a significant decrease in sweating. In another randomised controlled trial, patients with breast cancer were treated with black cohosh or placebo, followed by crossover, to study the effect of black cohosh after placebo, but no improvement in hot flushes was noted in the black cohosh group. Importantly, the use of black cohosh has been specifically studied in combination with tamoxifen in premenopausal patients with breast cancer: women were given either tamoxifen or tamoxifen with black cohosh extract. In those treated with the combination of the two drugs, a significant reduction

in the frequency of hot flushes was noted. However, in the absence of comparison with a placebo, it is difficult to establish if this result was merely a placebo effect, as women felt that they were receiving a treatment for hot flushes. Although many clinical trials have examined the use of black cohosh in patients with breast cancer, robust clinical data can only be obtained from properly conducted randomised, placebo-controlled clinical trials. These can be difficult to undertake and patients are often inclined to self-medicate, which confounds results. In the few studies described here, there is currently insufficient evidence to support the use of black cohosh to alleviate menopausal symptoms in early breast cancer patients who have treatmentrelated menopause. That being said, the lack of progress in this area means that whether the treatment is actively harmful than anything else we might try is a different question altogether.

Shairoz Merchant, *Justin Stebbing Imperial College, London, UK

[email protected]

Book Prostate cancer: a practical guide

What Men Won’t Talk About… and Women Need to Know: A Woman’s Perspective on Prostate Cancer Glenda Standeven. Standeven Publications, 2014. Pp96. £5·88. ISBN 978-0981330716


What Men Won’t Talk About…and Women Need to Know: A Woman’s Perspective on Prostate Cancer by Glenda Standeven is a practical book, designed with a specific purpose—to help women whose husbands have prostate cancer. The slim book is written in an engaging, conversational style as if Standeven is sitting down and chatting with you over coffee, telling you about what happened when her husband was diagnosed with prostate cancer and after. It takes the reader through the whole arc of treatment, emphasising the importance of prescreening for men

who might find going to the doctor an unpleasant chore, through treatment, and onto recovery and beyond. The book does not shy away from the repercussions of prostate surgery, including the sexual and emotional ones. This is, by design, a very utilitarian book. It’s not going to stir your soul with deathless prose or peerless insight into the human condition. However, what it does offer is a clear, concise guide to dealing with a cancer diagnosis, from someone who has been there before, with the hope that people who read this book

can learn from the mistakes and troubles Standeven and her husband experienced. The style is loose, and packs in a great deal of information without feeling like a list or getting bogged down in unnecessary detail— and it can also be very funny. What Men Won’t Talk About does not transcend its status as a guide for couples dealing with prostate cancer, but what it does, is done well. Any cancer diagnosis might be frightening, especially for people who are uncomfortable with or unused to major medical procedures. It also offers a lot for those who might be Vol 16 February 2015

Black cohosh, hot flushes, and breast cancer.

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