Description of the condition
Breast cancer is the most common cancer and leading cause of cancer death amongst women worldwide, both in developed and developing countries (WHO 2011). In 2008, it accounted for 23% (1.38 million) of total new cancer cases and 14% (458,400) of total cancer deaths (Jemal 2011).
Varying incidence rates result largely from differences in reproductive and hormonal factors and the availability of early detection facilities (Jemal 2010). Standard treatment options for breast cancer include surgical interventions, chemotherapy, radiotherapy and endocrine therapy. In spite of the major attributes of standard therapies, patients suffer from severe side effects and psychological distress during adjuvant therapy (Markes 2006) and even after cessation of therapy.
Side effects differ depending on the mode of treatment. Surgery or radiation treatment is usually a primary cause of lymphoedema (Shapiro 2001) and post-mastectomy pain is also a common side effect. Radiotherapy causes short-term side effects such as fatigue and skin erythema and long-term side effects including lymphoedema, cardiac and pulmonary toxicities, brachial plexopathy and secondary cancer (Shapiro 2001; Truong 2004). Cytotoxic chemotherapy is also known to have substantial short- and long-term side effects (Partridge 2001). Short-term side effects occur during the course of treatment and are usually resolved within months of completion of the treatment (Zhang 2007). These include fatigue, emesis (vomiting), stomatitis, alopecia (loss of hair), temporary ovarian failure, depression, myelosuppression (bone marrow suppression), thromboembolism (blood clot inside of the vessel), myalgias (pain in the muscles) and neuropathy (pain and numbness in the limbs when the peripheral nervous system (outside of the brain and spinal cord) is damaged) (Frisk 2011; Markes 2006; Shapiro 2001). Long-term side effects often have a much later onset and may last for many years (Ramalingam 2002). These include permanent premature ovarian failure in premenopausal patients, weight gain, cardiac dysfunction, leukaemia and potential cognitive impairment (Ramalingam 2002; Shapiro 2001).
Endocrine treatment (e.g. tamoxifen or aromatase inhibitors) contributes to symptoms secondary to oestrogen withdrawal, the most common of which are vasomotor symptoms including hot flushes and night sweats. Breast cancer survivors generally experience vasomotor symptoms to a greater degree and they are often more distressing and of greater duration (Carpenter 2002) than women going through 'natural' menopause. The recommended duration for endocrine treatment is usually five years, however the side effects may lead to patients discontinuing potentially life-saving adjuvant treatment (Gibson 2009; Loibl 2011).
Description of the intervention
Both pharmacological and non-pharmacological interventions have been used to alleviate the side effects of treatments for breast cancer (Boardman 2012; Markes 2006; Zhang 2007). However, the clinical benefits of pharmacological interventions for managing the side effects of oncological therapies can be very limited since they can also produce secondary side effects themselves. For example, the administration of oestrogen to women with breast cancer for relieving menopausal symptoms and preventing osteoporosis (in the long term) is controversial, because it may contribute to an increased risk of breast cancer or even a new development of primary breast cancer (Shapiro 2001). Many women do not wish to experience further side effects caused by pharmacological agents, or want to take medication additional to their standard therapies (de Valois 2010).
Non-pharmacological interventions to manage treatment side effects appear to be preferred, and the use of complementary and alternative medicine (CAM) has been increasing amongst patients with cancer in recent decades (Cassileth 2001; Lu 2009). It has been reported that women with breast cancer are more likely to use CAM (Molassiotis 2005; Patternson 2002); this may be as high as 53% (Lewith 2002) to 87% (Kremser 2008), and they are more likely to use acupuncture (Chao 2009). This echoes an overall tendency: the steadily growing popularity of acupuncture in many Western nations (Hamilton 2008; Harkin 2007; Hope-Allan 2004; Schmincke 2008; Zhu 2009).
Acupuncture involves the insertion of fine, single-use, sterile needles in acupuncture points (or acupoints) according to traditional Chinese medicine (TCM) theory. The common forms of acupuncture include body acupuncture, auricular acupuncture and scalp acupuncture according to anatomical regions, and the methods of manipulation may differ from manual to electroacupuncture (Qiu 1993).
With respect to safety, acupuncture appears to have a favourable safety profile if it is performed by a qualified and experienced practitioner (NCCAM 2006). One large study reported only 43 minor adverse events (such as nausea, dizziness, heavy sweating, mild bruising, pain and bleeding) associated with 34,407 treatments and no serious adverse events (MacPherson 2001).
How the intervention might work
How acupuncture works to eliminate the side effects of cancer treatments for breast cancer is still unknown, however emerging literature suggests acupuncture might work through several pathways. For example, acupuncture may induce body signals that are transmitted to the central nervous system (CNS), which in turn activates anti-inflammatory signals and pain relief processes through both humoral and neural mechanisms (Cho 2006; Sekido 2003). This sheds some light on how side effects can be plausibly managed by acupuncture.
Since the 1970s, it has been established that acupuncture may influence pain mediators through the release of neurotransmitters, such as ß-endorphin and endogenous opioids in the CNS (Cabýoglu 2006; Lin 2008; Ma 2004). The endogenous opioid-mediated mechanisms of acupuncture seem to be well understood (Han 2004).
It has been suggested that acupuncture initiates anti-inflammatory pathways in addition to opoid-mediated pathways. Animal studies have demonstrated that electroacupuncture may induce anti-inflammatory properties at both peripheral and central pain (i.e. nociceptives) sites (Lee 2006; Moon 2007). Prostaglandin E2 produced in the local inflammatory site is essential in initiating and maintaining inflammatory hyperalgesia (Shahed 2001). Clinical research has shown that electroacupuncture therapy seems to have a pain relief effect which might be associated with decreased measures of prostaglandin E2 in urine samples (Lee 2009).
Immune functions may also be involved when using acupuncture. Some animal studies have shown that bilateral electroacupuncture stimulation (at acupuncture point ST36) for three consecutive days enhances splenic natural killer (NK) cell activity (Yu 1998), while acupuncture (at BL23 points) for 20 days increases the ratio of NK cells to T lymphocytes in the spleen of mice after day seven (Okumura 1999).
A Japanese study suggested that acupuncture influenced the immune system through leukocyte and lymphocyte subpopulations in human peripheral blood (Takahashi 2009). In addition, a Chinese study showed that patients assigned to adjuvant electroacupuncture with chemotherapy had no significant changes in their T cell subpopulations, NK activity, immunoglobulin and leukocyte counts at the end of the fourth course of chemotherapy, in comparison with those who had chemotherapy without electroacupuncture in a control group (Ye 2004). This adds value in supporting the hypothesis that electroacupuncture might minimise the potential side effects of chemotherapy.
Studies have shown that the attributive effects of acupuncture are comprehensive, spanning from modulating an immunosuppressed or immunoactivated condition through the immune system to having an impact on the CNS (Lewith 2005; Ma 2004).
Why it is important to do this review
Improvements in early diagnosis and treatment have increased the life expectancy of women with breast cancer. In turn, this has led to specific problems being encountered by long-term breast cancer survivors. There has been a shift of emphasis to focusing on the negative impact of treatment on patients' quality of life, especially from long-term side effects (Pinto 2011), as well as the increased use of healthcare resources (Loibl 2011).
The use of CAM amongst cancer patients or survivors is due to the desire to increase the body’s ability to fight cancer or improve physical and emotional well-being (Molassiotis 2005). An Australian survey on women with breast cancer reported that: "common reasons for use included improving physical (86.3%) and emotional (83.2%) well-being and boosting the immune system (68.8%)" with 49.2% specifically reporting to "reduce treatment side effects" (Kremser 2008). Another large survey stated that acupuncture was effective (40%) or very effective (7.7%) for modulating immune functions, relieving pain, alleviating menopausal symptoms or managing other discomforts in the breast cancer population (Cui 2004). However, there has been a lack of scientific evidence to support these claims or empirical experience reported by patients or survivors.
Furthermore, despite the popularity of acupuncture in cancer patients (de Valois 2010; Frisk 2011; Hervik 2010; Lu 2009; Shen 2000; Sima 2009), acupuncture has not met with wide approval amongst medical professionals and there has been poor communication between patients and medical carers (Lu 2009; Molassiotis 2005). Patients and healthcare professionals need more information on the effectiveness and safety of complementary medicine interventions.
A few systematic reviews on the role of acupuncture in managing side effects in women with breast cancer have been previously conducted (Chao 2009; Ezzo 2006; Lee 2009a). However, some reviews focused on specific symptoms and there was a lack of consideration of the unique features of TCM philosophy that underpin acupuncture, when the tools of evidence-based practice were applied to assess its effectiveness.
It has been suggested that acupuncture as a treatment to control side effects may potentially alleviate conventional therapy-induced side effects and improve quality of life (Price 2012).