Breast Cancer and Botanical Medicine
Breast Cancer and Botanical Medicine
Part II of a Series
By Steven Gomberg, LAc, CCN, RH (AHG), and Brandon Horn, PhD, JD, LAc. The authors are licensed acupuncturists and board-certified oriental medicine practitioners for the Eastern Center for Complementary Medicine, Los Angeles; they report no financial relationships relevant to this field of study.
[Editor's note: The following article is a continuation of the article published in the September 2008 issue of Alternative Therapies in Women's Health.]
Possibly the most important factor in tumor development is its microenvironment.1 Indeed, recent research has shown the possibility of reversing even aggressive tumors by adjusting the microenvironment. As one researcher commented, "our observations highlight the potential utility of isolating the factors within the hESC [human embryonic stem cell] microenvironment responsible for influencing tumor cell fate and reversing the cancerous properties of metastatic tumor cells, such as melanoma." The accumulating data on microenvironments imply that cancer therapies targeting the tumor itself, while leaving the original terrain intact, could possibly be less effective and leave the patient more susceptible to recurrences.
Most potential etiologic factors can be roughly categorized as environmental toxins (i.e., non-biological agents), infectious agents (biological), or internal issues such as digestive or emotional stressors.2 While environmental toxins, dietary factors, and, to some degree, chronic emotional stress are somewhat established etiological factors in conventional literature, infectious agents are a relative newcomer. Interestingly, there is a growing body of evidence implicating infectious agents, particularly viruses, in some breast cancers.3 According to Chinese medicine theory, one etiology of tumorigenesis is direct or indirect alterations in DNA by infectious agents. While the association is still unclear from a conventional standpoint, plausible mechanisms exist for both direct alterations of DNA (e.g., viral) as well as collateral DNA damage caused by immunological defenses (e.g., reactive oxygen species [ROS]).
Further complicating matters, the etiology of many cases of breast cancer appears to be multifactorial. For example, having a BRCA gene mutation does not, in and of itself, always result in breast cancer. Treating identifiable etiological factors is, therefore, extremely important.
Where information on exposure to particular types of carcinogenic compounds is available, herbs may be helpful in counteracting their effects. However, in many cases the exposures are unknown. Therefore, it is generally useful to take a more indirect approach that involves improving the body's detoxification capacity and downregulating hormone receptors, where appropriate. Research is demonstrating that herbs may be useful in this regard. For example, Scutellaria barbata increases the expression of the gene for glutathione S-transferase (GST) by 2.5-3.0-fold.1 As GST increases phase II metabolism of xenobiotics, S. barbata may prove helpful in a broader xenobiotic/mutagen prevention strategy. At the same time, it inhibits intratumoral aromatase expression in certain cancer cells, and so may help in other ways to prevent the promotion of tumor development.4
For protecting against radiation-induced damage, Curcumae longa may be very useful. The herb paradoxically protects normal cells from radiation while sensitizing cancer cells to radiation.5 In addition, it may be prudent to administer this prophylactically, or other radioprotective substances to women undergoing any kind of imaging involving ionizing radiation such as mammography. We recommend 500 mg tid of a 5:1 concentrated aqueous extract for a course of 21 days beginning seven days before the imaging is scheduled.
Addressing infectious agents is a complicated discussion from an herbal standpoint. In Chinese medicine, there is an intricate theoretical basis for the identification and eradication of infections. If an infectious etiology is suspected, we can think about using herbs that combine antitumor and antimicrobial properties. Andrographis and Scutellaria baicalensis are examples of herbs that demonstrate both strongly antitumor and antimicrobial properties.
In addressing digestive and immune function, adaptogenic herbs are often employed. These herbs tend to have an overall positive effect on resistance to external stressors. Some of the more popular and effective adaptogens include astragalus, Poria cocos, and eleutherococcus. Astragalus, for example, has general antitumor properties and has also been shown to have beneficial effects on the gut. It was shown to both prevent and treat colitis,6 and help restore intestinal microfloral balance.7,8 P. cocos also has digestive and immunological benefits with the additional function of being a mild diuretic. It also has antitumor properties.9
Emotional factors are generally involved in breast cancer, whether part of the etiological factors or as a result of a diagnosis. Therefore, addressing a patient's psychological state is very important. Several herbs are very helpful in this regard and, in addition to having anxiolytic properties, they also have other mechanisms that help fight various breast tumors. Examples of some of the important herbs in this category are Passiflora incarnata and chrysanthemum. Both contain chrysin, an anxiolytic flavonoid that has been shown both to inhibit aromatase10 and metastasis.11
Honokiol, a bisphenolic compound isolated from the Chinese herb Magnolia grandifloris, has also demonstrated potential benefits in treating affective disorders such as anxiety and depression.12 In addition, it has novel anticancerous activities. For example, honokiol was recently shown to downregulate phospholipase D,13 a survival signal for some breast cancers (e.g., MDA-MB-231) that suppresses apoptosis. It also decreases epidermal growth receptor EGFR, which is commonly over-expressed in breast cancer, and induces caspase-dependent apoptosis. It was found to have a time- and concentration- dependent growth inhibition in both estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines, as well as in drug-resistant breast cancer cell lines such as those resistant to adriamycin and tamoxifen. Honokiol also shows promise in combination therapies. For example, it was shown to synergistically enhance the effect of lapatinib (Tykerb®),14 adriomycin,15 and rapamycin on breast cancer cells.14 Honokiol also downregulates Ras activity, which may be overexpressed in many breast cancers due to the expression of growth factor receptors which signal through Ras.16
Maintaining Integrity of the Body
Many therapies for cancer are fairly aggressive and can damage healthy tissue. Adaptogens are utilized to help maintain the integrity of normal cells during the assaults on the tumor tissue. Adaptogens are herbs that have a regulatory effect on the body to help it "adapt" to various stressors. Given their function, questions have been raised about an adaptogen's ability to protect a tumor as well. While a plausible concern with some adaptogens, others have significant antitumor activity. Eleutherococcus senticosa, for example, can be used concurrently with chemotherapy to mitigate side effects such as nausea, dizziness, and loss of appetite in patients undergoing treatment with cyclophosphamide.17 Eleutherococcus also helps to restore immunologic function in patients undergoing myelosupressive chemotherapeutic regimes.18 In addition to strengthening the patient, E. senticos also inhibits metastatic potential and has antitumor17 and antiviral19 activity. Other useful adaptogens in oncology include astragalus and ganoderma.20,21
Administration of Herbs
In Chinese medicine, herbs are commonly administered in formulas of 5-20 herbs. The framework of an herbal formula should be determined by the patient's condition. For example, a strong person with an aggressive tumor may have 70% of the formula attacking the tumor, 20% dealing with the etiology, and 10% providing adaptogens. A patient that is debilitated, perhaps from multiple chemotherapy rounds, may require 70% adaptogens, 20% antitumor, and 10% of the formula addressing etiology. This is where clinical judgment comes in. Of course many herbs overlap categories, so these percentages are only a rough guide.
Next are issues with herb quality. As noted in the peer-reviewed literature, and especially so for Chinese patent medicines, it is of paramount importance that herbs be tested for heavy metals and other environmental toxins. The form of extraction is also important. In many cases, oral administration of aqueous extracts are used; however, some functions of herbs can only be accessed with other extraction methods (e.g., ethanol) or other routes of administration (e.g., injection or enema). When considering adjuvant administration of herbs in the treatment of cancer, it is prudent to use herbs that have been standardized to specific active constituents. Identifying and recommending companies that adhere to Good Manufacturing Practices is of great benefit to patients.
In choosing the appropriate herbs to administer, some clinicians use laboratory tests and tissue pathology, whereas others combine these tests with traditional Chinese medicine diagnostic methods such as tongue and pulse diagnosis. Generally in cancer therapy, dosages of administered herbs can be quite high; therefore, it is prudent to concurrently monitor liver and kidney function. While the tolerance of herbal formulas is generally quite good, there have been rare instances of contamination or of the administration of an inappropriate species that have resulted in serious complications. In most cases, these risks can be avoided through prudent monitoring and should not be a deterrent to using herbs. In fact, many of the herbs used in therapy are both nephroprotective and hepatoprotective and allow for much higher tolerance of aggressive therapies such as chemotherapy. Ganoderma is one example of an herb used in breast cancer therapies that is both nephroprotective22,23 and hepatoprotective.24
Conclusion
Breast cancer is a disease exhibiting a variety of different etiological and pathological mechanisms. The current paradigm, in which the main focus of treatment is the tumor itself, may not be the most effective approach. Recent data suggest that the tumor microenvironment may be of equal if not greater importance.
Chinese medicine historically emphasizes both treatment of the tumor itself and the microenvironment. As such, Chinese medicine treatments may be a very useful adjunct in the treatment and prevention of breast and other cancers. Biomedical research into the actions of herbs traditionally used in the context of breast cancer has revealed a number of novel and seemingly effective compounds. This research has also confirmed a number of mechanisms for their purported efficacy (e.g., inhibiting angiogenesis, upregulating p53, selectively inducing apoptosis of tumors, inhibiting tumor and peripheral expression of aromatase, increasing antitumor immune activity, and reducing side effects of conventional therapies). While-large scale human trials are just beginning, given the wealth of historical information on the safety and efficacy of various herbs (some of them having been used for thousands of years), an herbal regimen should be strongly considered as an additional and potentially effective tool in the treatment of breast cancer.
By utilizing herbs that have both historical data and modern research demonstrating potential mechanisms for efficacy, we can maximize the chances of favorable outcomes while minimizing discomfort associated with conventional therapies. Where herb formulas are combined with conventional therapies, it is prudent to monitor the patient closer during the initial stages of administration for both efficacy (improvements in tumor markers or size) and safety (kidney and liver function). As with pharmaceuticals, herbs contain powerful chemical compounds. Therefore, even where biomedical research supports the use of a single herb or component, combinations with other herbs or pharmaceuticals can produce new chemical compounds that differ from the original chemicals.
However, just as the lack of definitive data on the combined effects of most pharmaceuticals does not prevent their prescription, a lack of data on the combined effects of herbs and drugs should not be a hindrance to their use. The same prudent monitoring that allows for millions of successful prescriptions annually of untested pharmaceutical combinations can enable us to successfully apply the combined use of herbs and pharmaceuticals. With proper monitoring, herbs can be a substantial asset both in the treatment and prevention of breast cancer.
References
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Gomberg S, Horn B. Breast Cancer and Botanical Medicine. Alter Ther Women’s Health. 2008;10:73-77.Subscribe Now for Access
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