Abstract
With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patientsʼ wellbeing and quality of life, reducing stress, and improving patientsʼ mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle.
Key words: complementary and alternative medicine, CAM, integrative medicine, breast cancer, naturopathic treatment, phytotherapy
Abstract
Zusammenfassung
Mit verbesserter Prognose und Fortschritten in der Diagnostik und Therapie des Mammakarzinoms rücken Aspekte wie Lebensqualität und Nebenwirkungsmanagement bei der Mammakarzinombehandlung in den Fokus der Ärzte und Therapeuten. Therapie- oder erkrankungsbedingte Nebenwirkungen mindern häufig die Lebensqualität und können damit zu einer zusätzlichen Beeinträchtigung der Patientin führen. Nicht selten sind Non-Compliance oder sogar Therapieabbruch die Folge. Studiendaten zeigen, dass durch Methoden der Integrativen Medizin therapie- und krankheitsbedingte Nebenwirkungen reduziert werden können. Eine Steigerung des Wohlbefindens und der Lebensqualität, der Abbau von Stressbelastungen und eine Verbesserung der Stimmung, des Schlafes und der Krankheitsbewältigung sind nachgewiesen. Alle Nebenwirkungen der Integrativen Medizin zu beleuchten, würde den Umfang des hier vorliegenden Reviews übersteigen, sodass sich dieser Artikel auf kurzfristige Nebenwirkungen, die in der Regel zeitlich begrenzt während oder nach der lokalen bzw. systemischen Therapie auftreten, fokussiert. Der Fokus richtet sich speziell auf Mind-Body-Medizin, Akupunktur und die klassischen Naturheilverfahren nach Sebastian Kneipp als integrative Therapieoptionen. Letztere umfassen die Hydrotherapie, Phytotherapie, Ernährungstherapie, Bewegungstherapie und Ordnungstherapie.
Schlüsselwörter: Komplementäre und Alternative Medizin, CAM, Integrative Medizin, Mammakarzinom, Naturheilverfahren, Phytotherapie
Introduction
Local treatment of breast cancer consists of surgery and/or radiation therapy; other treatments include drug therapies such as chemotherapy, antihormone therapy and targeted therapies 1. With improved prognosis due to advances in the diagnosis and treatment of breast cancer, physicians and therapists now also focus on aspects such as quality of life and the management of side effects from breast cancer treatment 2. Great strides have been made in recent years in understanding molecular tumor biology, therapy mechanisms and patient characteristics. A number of new molecular tests and modern therapies have emerged, not only in the field of anti-HER2 therapy, but also to treat triple-negative and hormone receptor-positive patients. New therapies are being developed which aim to overcome trastuzumab resistence by influencing the PI3 K pathway or inhibiting the cell cycle 3.
New therapies for breast cancer have improved survival rates but have also resulted in an increase in side effects and interactions. The cancer diagnosis is not the only physical and psychological burden on patients. Cancer treatments often have considerable side effects which reduce patientsʼ quality of life, creating an additional burden for patients 4, 5, 6. Moreover, breast cancer patients now spend significantly longer periods in therapy 7. Therapy- or disease-related side effects often reduce the patientʼs quality of life and have a significant adverse impact on the patient 8. The consequence may be non-compliance or even discontinuation of therapy 9, 10. Around 31 % of breast cancer patients discontinue antihormone therapy with an aromatase inhibitor in the first 5 years, the majority because of unpleasant side effects 11, 12.
The EvaluateTM study included a total of 5045 patients with hormone receptor-positive breast cancer, enrolled between January 2008 and December 2009. The study offers a good overview of therapy management in the routine care of postmenopausal patients with hormone receptor-positive breast cancer, including information on therapy compliance and on patient satisfaction with the provision of information and how the information is conveyed 13.
Both local and systemic therapies to treat breast cancer are associated with side effects, classified into short-term and longer term consequences. This is not a rigorous differentiation as the borders between the two are often blurred. Variations are of course always possible. Because of the large number of side effects from treatment and of potential integrative medicine therapies, this review cannot focus on all types of complaints and the potential integrative medicine methods used to combat them. The article focuses on methods of mind-body medicine, acupuncture and naturopathic medicine as complementary therapies. This review exclusively considers short-term side effects (Table 1), which occur for a limited period of time during or after therapy. Such side effects include impaired wound healing, edema and radiation erythema after local therapy, nausea and vomiting, mucositis and stomatitis, and diarrhea and constipation after systemic therapy.
Local therapy | |
Surgery
|
Radiation therapy
|
Systemic therapy | |
Chemotherapy
|
Antihormone therapy
|
Antibody therapy
|
Osteo-oncologic treatment
|
The prevalence of side effects of breast cancer treatment reported in the literature varies greatly and differs from study to study (Tables 2 to 4) 1, 14, 15.
Surgery (breast-conserving surgery, resection, sentinel lymph node biopsy, axilla dissection) | |
| |
76 % | Hematoma/seroma |
31–71 % | Sensory disturbances |
57 % | Scarring/fatty tissue necrosis |
24–56 % | Swelling/lymphedema |
12–51 % | Pain |
2–51 % | Limited range of movement |
17–33 % | Strength impairment |
| |
4–17 % | Impaired wound healing |
3–15 % | Wound infection |
Radiation therapy (conventional radiation therapy, brachytherapy) | |
| |
80–90 % | Erythema/radiodermatitis |
30–80 % | Fatigue |
0.2–70 % | Telangiectases |
2–67 % | Breast fibrosis/breast deformity |
43–54 % | Locoregional dysesthesias |
2–51 % | Breast edema |
5–36 % | Hyperpigmentation |
35 % | General malaise |
0.4–33 % | Lymphedema of the arm |
10–15 % | Wet desquamation |
| |
< 1 % | Symptomatic pneumonitis |
< 1 % | Pulmonary fibrosis/myocardial fibrosis |
< 1 % | Osteoradionecrosis of the ribs |
< 1 % | Axillary plexus injury |
Targeted therapy (trastuzumab [Herceptin®], lapatinib [Tyverb®], pertuzumab [Perjeta®], trastuzumab emtansin [T-DM1, Kadcyla®], bevacizumab [Avastin®]) | |
| |
16–67 % | Gastrointestinal complaints |
27 % | Muscle and joint pain |
23–24 % | Skin rash/erythema |
21 % | Headache |
12–15 % | Fever/chills |
10–14 % | Flu-like symptoms |
11 % | Dizziness |
> 10 % | Blood count changes (anemia, thrombopenia, leukopenia) |
1–10 % | Fluctuations in blood pressure |
> 10 % | Cardiac arrhythmia |
1–10 % | Cardiac insufficiency |
| |
< 0.1 % | Pericardial effusion/pleural effusion |
Osteo-oncologic treatment (zoledronic acid [Zometa®, Aclasta®], denosumab [Xgeva®, Prolia®], ibandronate [Bondronat®], alendronate [Fosamax®], risedronate [Actonel®]) | |
| |
> 10 % | Hypocalcemia and hypophosphatemia |
> 10 % | Flu-like symptoms |
9 % | Headache |
3–7 % | Fever/chills |
3 % | Bone and joint pain |
1–10 % | Gastrointestinal complaints |
1–10 % | Renal function disorders |
1–10 % | Anemia |
1–10 % | Skin rash |
| |
< 0.1 % | Jaw osteonecrosis |
< 0.1 % | Cardiac arrhythmia |
Chemotherapy (epirubicin, cyclophosphamide, paclitaxel, carboplatin) | |
| |
10–100 % | Hair loss |
< 10 % to > 90 % | Nausea/vomiting (depending on the emetogenicity and antiemetic therapy) |
1–84 % | Neurotoxicity |
16–75 % | Cognitive impairment (“chemo brain”) |
20–70 % | Insomnia |
30–60 % | lethargy, chronic fatigue |
25–40 % | febrile neutropenia (without previous cytostatic therapy) |
10–40 % | Inflammation of the mucous membranes (mucositis, stomatitis) |
5–60 % | Diarrhea |
20–30 % | Depressive episodes |
| |
2–20 % | Anemia |
0.8–4 % | Cardiotoxicity in the adjuvant setting |
< 2 % | Acute hypersensitivity reaction |
Antihormone therapy (letrozole, tamoxifen, exemestane, anastrozole, fulvestrant) | |
| |
34–40 % | Hot flushes, sweating |
30–24 % | Bone, joint and muscle pain |
20–30 % | Depressive mood |
> 10 % | Fatigue |
6–12 % | Osteoporosis |
1–10 % | Increased appetite and weight gain |
1–10 % | Insomnia |
1–10 % | Nausea |
1–10 % | Hair loss, dry skin |
1–10 % | Hypercholesterolemia |
5–9 % | Vaginal bleeding |
| |
2–4 % | Thrombosis |
1–2 % | Cardiovascular events |
Integrative medicine is a complementary treatment offered to breast cancer patients to alleviate therapy- and disease-related side effects 16, 17, 18 and improve patientsʼ quality of life 19, 20, 21. Improved wellbeing, reduced stress and improvements in mood, sleeping and coping with disease have also been reported 16, 17, 19. Various methods are used as complementary therapies to relieve the symptoms of tumor disease and the side effects of oncologic therapy. However, none of these can replace supportive therapies based on established medical guidelines. It is also important to be aware of potential contraindications and interactions, which requires a good understanding of integrative medicine 1, 2, 22.
Integrative medicine in gynecologic oncology has many aims (Table 5).
|
|
|
|
|
|
The increased evidence for the efficacy of integrative interventions has resulted in recommendations being included in the guideline on the treatment of breast cancer issued by the Association of Scientific Medical Societies in Germany (AWMF), the German Cancer Society (Deutsche Krebsgesellschaft e. V.) and German Cancer Aid (Deutsche Krebshilfe e. V.): the Interdisciplinary S3-Guideline on the Diagnosis, Therapy and Follow-up Care in Breast Cancer (Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms) 1 and the recommendations for action issued by the Breast Commission of the German Gynecologic Oncology Study Group (Arbeitsgemeinschaft für Gynäkologische Onkologie e. V. Kommission Mamma) 2.
It is difficult to achieve the same level of evidence for individual recommendations made to patients in integrative medicine as for evidence-based standard therapies in senology or gynecologic oncology because there are currently almost no standards, norms or benchmarks in the field of integrative medicine which are considered accurate (e.g. guidelines, medical treatment recommendations, standards). Standardization, structuring and the introduction of criteria used for quality assurance in oncology could provide greater safety and better quality for patients and improve the overall acceptance and value of integrative medicine 23.
Unless otherwise specified, the following suggestions for integrative therapies in breast cancer were obtained from randomized controlled studies, systematic reviews, or meta-analyses 24, 25, 26, 27, 28, 29, 30.
Short-term Side Effects of Local Therapies
Lymphedema
Exercise therapy
Physical exercise is increasingly being recommended to patients with lymphedema. The current data shows that physical exercise is not, as was previously assumed, a contraindication; on the contrary, sport can even have a protective effect. These findings are largely based on studies carried out in breast cancer patients and refer to resistance training, aerobic exercise and stretching exercises 31. Other forms of exercise such as pilates, yoga, tai chi, qigong and relaxation techniques have not yet been adequately studied and are therefore not currently recommended. Theoretically, there is no reason why patients should not do exercise in which movements are calm and unhurried. Physical exercise should be done under expert supervision to ensure a proper warm-up, cool-down and an appropriate intensity and selection of exercises.
A recent, 3-arm, randomized controlled study (n = 62), the first study to compare the safety and efficacy of different intensities of resistance training (moderate-high intensity vs. low-load exercise), reported significant improvements in muscle strength, muscle endurance and quality of life in terms of physical functioning compared with standard therapy (no exercise). There was a trend to better results among the group who did high-load exercise, but there were no differences between exercise groups with respect to severity of lymphedema symptoms and no adverse events 32.
Patients with lymphedema after breast cancer surgery can safely do upper body resistance exercise. Physical exercise had a protective effect on lymphedema symptoms 31.
Acupuncture
Lymphedema is not a contraindication for acupuncture in the affected arm. Data on the safety of acupuncture treatment used in affected extremities after surgery were published for the first time at the end of 2011. In 2013, the same study group around Barrie R. Cassileth published data from a pilot study on the efficacy of acupuncture to treat lymphedema of the upper limbs 33. Lymphedema was reduced by 30 % in one third of breast cancer patients treated in the study. The respective puncture sites on the skin were disinfected prior to every needle application 33 (Table 6).
Symptoms | Lymphedema | Impaired wound healing, radiation-induced skin damage |
---|---|---|
Mind-body medicine |
|
|
Acupuncture |
|
|
Exercise therapy |
|
|
Phytotherapy |
|
Impaired wound healing and radiation-induced skin damage
Phytotherapy
Phytotherapeutic agents such as calendula, chamomile or hamamelis are used to treat impaired postoperative wound healing, hyperproliferative scars or radiation-induced skin damage 30, 34, 35. These agents can be applied topically in the form of baths, poultices, salves, creams or gels. The wound-healing and anti-inflammatory properties of phytotherapeutic drugs have a beneficial impact on the process and improve the cosmetic result 34, 35, 36 (Table 6).
A 20 % calendula ointment has been recommended for the prevention of radiation dermatitis after radiation therapy 30. The ointment is thinly applied to the skin several times per day. The 20 % calendula ointment was found to be superior to topical therapy with trolamine for the prevention of radiation-induced skin damage. A meta-analysis of 254 breast cancer patients receiving radiation therapy found a significantly lower incidence of radiation dermatitis ≥ grade 2 in the Calendula group compared to the Trolamine group (41 vs. 63 %; p < 0.001) 30.
Short-term Side Effects of Systemic Therapies
Mucositis and stomatitis
Chemotherapy and cachexia can lead to painful changes in the mucosa of the mouth, throat and esophagus which make eating more difficult for affected breast cancer patients. In addition to antiseptic and analgesic mouth rinses, some naturopathic therapies have been found to be effective in practice 37, 38, 39.
Nutrition and dietary interventions
Various dietary strategies for the management of side effects which have been proved to be effective in practice and which can be applied without the risk of addditional undesirable side effects are described below. The boundaries between dietary interventions and phytotherapy are blurred.
When mucous membranes are inflamed, it is important to minimize mechanical and physical stresses on the membranes, e.g. only finely ground wholemeal and wholegrain products should be consumed, for example in the form of oat-spelt flakes, and food consumed should be no more than lukewarm. Because oats (including oat milk) have high levels of β-glucans, the ingestion of oat-based foods can potentially offer some protection for gastrointestinal mucosa 40. Maintaining a consistent oral hygiene is beneficial, including frequent rinsing with suitable herbal decoctions, e.g. sage leaf tea. Very good results have been reported for sea buckthorn oil, of which a small amount (a coffee-spoonful) is taken into the mouth, distributed around the oral cavity and spat out again after a brief time in which it is allowed to take effect 41. Sea buckthorn oil strongly stains the oral cavity and changes the color of the tongue, making tongue diagnosis as used in traditional Chinese medicine difficult. In patients with gastritis and esophagitis a concomitant ingestion of flaxseed gruel or flaxseed tea is recommended 42. Enzyme-rich foods which are also low in acidity (e.g. papaya) also promote healing as do mild preparations of long-simmered lentils (ayurvedic dahl recipes) 43 and sweet potato or parsnip purees.
Phytotherapy
Liquid extracts or tinctures of essential oils of chamomile, arnica flowers, sage leaves and myrrh can relieve symptoms of mucositis and stomatitis (Kamillosan®, Dr. Hauschka® sage mouthwash, Hetterich® tincture of myrrh) 37, 38, 39. They contain anti-inflammatory, antibacterial and antiviral agents. Treatment consists of rinsing the oral cavity or dabbing the inflamed area with the application several times per day. In addition to ready-to-use preparations, home-made sage or chamomile teas are also effective and simple to prepare. A Cochrane review on the prevention of oral mucositis in antitumoral therapy reported positive evidence for the local application of aloe vera extracts (e.g. gargling 2 ×/d for at least 20 s with Aldiamed® mouthwash) 37, 39.
Nausea and vomiting
Breast cancer patients often suffer from nausea and vomiting during chemotherapy or postoperatively. In addition to standard drug therapies to alleviate symptoms, integrative medicine offers an important complementary approach (Table 7).
Symptoms | Mucositis/stomatitis | Nausea/vomiting |
---|---|---|
Mind-body medicine |
|
|
Acupuncture |
|
|
Phytotherapy |
|
|
Nutritional therapy |
|
|
Mind-body medicine
Jacobsonʼs progressive muscle relaxation is recommended during chemotherapy to reduce the duration and possibly also the incidence of nausea and vomiting. However this relaxation method does not appears to affect the intensity of nausea 44.
Acupuncture
The use of acupuncture to alleviate postoperative and chemotherapy-induced nausea/vomiting is becoming more accepted based on increasing evidence. The Breast Commission of the Gynecologic Oncology Study Group 45 therefore recommends the use of acupuncture to treat nausea both postoperatively and during chemotherapy. A Cochrane review by Lee and Fan published in 2009 included 40 studies with 4858 participants in whom the acupuncture point Pericardium 6 was stimulated. Compared with sham acupuncture, acupuncture point stimulation significantly reduced nausea, vomiting and the need for antiemetic drugs 26. Another review on the treatment of chemotherapy-induced nausea and vomiting found that acupuncture point stimulation reduced the incidence of acute vomiting 27. The most commonly used acupuncture points are: Stomach 36, Conception Vessel 12, Pericardium 6, Large Intestine 4 and Liver 3.
Nutrition and dietary interventions
Ginger has been found to have mildly antiemetic properties. Other recommended antiemetics include bitter herbal remedies, e.g. Centaurium erythraea, essential oils and fresh air. Breast cancer patients can add fresh ginger to their food and/or drink it in the form of an infusion 46.
Phytotherapy
Ginger (Zingiber officinale) was used as an herbal antiemetic long before the introduction of modern antiemetic drugs. It acts as an antiemetic and cholagogue, stimulates the flow of saliva and gastric juices, and promotes intestinal peristalsis. Controlled studies found ginger to be superior to placebo and equivalent to reference drugs 29, 47, 48. In a study of 576 breast cancer patients, Ryan et al. showed that ginger, administered in doses of 500–1000 mg/day, was able to reduce the severity of acute nausea 48. In another study of 100 breast cancer patients with advanced stage disease, ginger was effective in reducing the prevalence of acute nausea 6 to 24 hours after chemotherapy 29. The effect occurs through mild inhibition of 5-HT3 receptors, which are significantly involved in processing and reinforcing emetic stimuli 49. It is important to watch for interactions with aprepitant (Emend®) when using ginger because of the potential antagonist effects 50.
Ginger in the form of tea or ginger water can be prepared by breast cancer patients themselves. It is also available in tablet form (e.g. Zintona® capsules, patients with acute symptoms to take 1 capsule 1 h prior to chemotherapy, followed by 2 capsules every 4 h, after symptoms have improved 2 × 1 capsule per day).
Teas containing a mix of chamomile (Matricaria chamomillae), balm (Melissa officinalis) and peppermint (Mentha piperita) can also help alleviate symptoms (suggested tea mixture: 20 g chamomile blossoms, 20 g peppermint leaves, 20 g lemon balm leaves, to be mixed with ginger tea if required) 51, as can a combination of angelica, caraway, milk thistle, balm, peppermint, greater celandine and licorice (Iberogast®, 3 × 20 drops per day before meals). Sniffing essential oils such as vanilla, coriander, ginger or mint can also bring relief.
Diarrhea and constipation
Integrative medicine offers a number of effective therapeutic options to treat diarrhea or constipation (Table 8).
Symptoms | Diarrhea | Constipation |
---|---|---|
Mind-body medicine |
|
|
Acupuncture |
|
|
Exercise therapy |
|
|
Phytotherapy |
|
|
Nutritional therapy |
|
|
Nutrition and dietary interventions
Traditional household remedies are recommended to treat acute diarrhea; these include very fine medicinal clays for internal use, pectin-rich foods e.g. grated apples, carrot-potato puree, banana-rice puree 52, 53. In addition to water, fluid intake can include tannin-rich teas (rooibos, black and green tea), cocoa made with water, and mineral-rich vegetable broths 42, 46.
After excluding other causes, patients with constipation after breast cancer therapy should increase their total fluid intake and the amount of dietary fiber they ingest. Breast cancer patients who are unable to eat many vegetables or fruits can take oat bran, wheat bran or psyllium (Plantago ovata) as fiber isolates or soaked dried fruit 54, 55. Natural flaxseed oil or olive oil and pre- and probiotic foodstuffs (e.g. Jerusalem artichokes, yoghurt, etc.) can also be beneficial 56. In addition to dietary changes, other useful therapies include hydrotherapy and physiotherapy, e.g. colonic irrigation, appropriate exercise, hydropathic treatments 42.
Phytotherapy
There are a number of phytotherapeutic agents available to treat symptoms in patients with acute or subacute diarrhea following tumor therapy. Tannin-rich substances such as black or green tea and dried blueberries (Myrtilli fructus) have astringent properties, reduce gastric acid secretions, and prolong intestinal transit times. Proposed treatments include taking 5–10 g dried blueberries every day and only swallowing them after chewing them to a pulp; or, adding 1 teaspoon black tea or ½ teaspoon green to 150 ml boiling water (maximum quantity per day not to exceed 2 l), allowing the mixture to stand for 15–20 min and drinking it throughout the day. Use of psyllium husks (Psylli semen) have also been reported to be effective. Mix 10–20 g psyllium with water at a ratio of 1 : 10 and take up to 3 times per day or use ready-made products (Agiocur®, Mucofalk®, Pascomucil®). Pectins from apples and carrots are also helpful (Diarrhoesan®, Moroʼs carrot soup) 46, 57.
The use of phytotherapeutic bulking agents is recommended to relieve the symptoms of constipation (wheat bran: 1–3 × 2 tablespoons per day; psyllium: 1–2 teaspoons per 1 bowl of soup, no milk; or flaxseeds: take 1–3 × 1 tablespoons together with water) combined with sufficient fluid intake 46. Laxatives such as Aloe vera extract, alder buckthorn bark, rhubarb root or senna leaves should only be taken for short term periods (maximally 1–2 weeks) and under medical supervision, as the loss of calcium resulting from the use of laxatives can increase intestinal hypomotility 42.
Conclusion
The data on acupuncture, phytotherapy and mind-body medicine-based approaches clearly indicate that these therapies can provide effective short-term relief of disease- and therapy-related side effects. These therapies can help to ensure that treatments are tolerated better, improving compliance and allowing treatment to be completed according to medical guidelines. A diagnosis of cancer often brings a traumatic sense of alienation from oneʼs own body and powerlessness. Body-focused mindfulness and meditation exercises, gentle yoga and moderate exercise allow patients to consciously reconnect with their own physicality.
The patientʼs daily diet offers an additional possibility to strengthen the patientʼs organism and resilience through the optimal provision of all necessary substances. Tried-and-tested means offering relief of side effects caused by cancer treatments are also available. Some of them have been outlined here. As an important part of the patientʼs life and lifestyle, nutrition can be a source of pleasure, contribute to the patientʼs quality of life, and act as a tasty “medicine”.
As an important part of integrative medicine, phytotherapy is useful to relieve symptoms of tumor disease and side effects of oncologic therapy and to increase patientsʼ quality of life. However, phytotherapy cannot replace supportive therapies based on established medical guidelines. It is important to be aware of possible contraindications and interactions, which requires a good knowledge of phytotherapy. If these principles are respected, phytotherapy can be successfully used as a complementary approach in gynecologic oncology.
Footnotes
Conflict of Interest None.
Supporting Information
References
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