Alternative Medicine
Research Proposal
Team Integrative Medicine and Cancer
Peter Frechette
Stephanie Galanie
Kevin Gu
Anna Hung
Sarah Kim
Kelsey Merrick
Krupa Nataraj
Jessica Nooralian
Mihir Patel
Jessica Stevens
Vivian Wang
Albert Zhou
GEMS2021
Alternative Medicine
Abstract
Due to the negative side effects of conventional cancer treatments, many patients are turning to less-understood complementary and alternative medicine (CAM) therapies. One commonly available and frequently inexpensive form of CAM is herbal dietary supplements. We will investigate breast cancer patients’ use and perception of herbal dietary supplements in the DC/Metro area. We will also determine the metabolic effects of commonly used supplements on cancer cells in vitro. This mixed-methods approach will provide a deep understanding of local breast cancer survivor perceptions of herbals and quantitative data regarding commonly used herbal dietary supplements. Ultimately, we plan to publicize our results either through a peer-reviewed journal or through an informational campaign.
Introduction
Every one in four deaths is caused by cancer, making it the second most common cause of death in the United States. In 2007, an estimated 2.5 million cancer cases were diagnosed in the United States alone. The National Institutes of Health estimates that about 206.3 billion dollars were spent on cancer-related costs in 2006.1 Cancer is a life-threatening disease that can affect anyone regardless of age, lifestyle, gender, or ethnicity.
Radiation and chemotherapy, common conventional cancer treatments, often kill healthy cells in addition to cancerous cells. This causes many side effects, including hair loss, nausea, vomiting, fever, immune system vulnerability, and fatigue.2 Even if a patient’s cancerous tumors can be destroyed through treatment, the survivor’s quality of life is usually significantly decreased. Activities once taken for granted—eating, taking a walk outside, or working a full-time job—are often sacrificed for treatment.
The drawbacks of conventional treatments cause many patients to seek alternatives. Complementary and alternative medicine (CAM) is becoming increasingly popular among the general population, especially among those with life-threatening illnesses such as cancer.3, 4 A study conducted in 2004 found that over half of the cancer patients surveyed began the use of one or more CAM modalities following cancer diagnosis.5 As CAM treatments become increasingly popular, cancer patients must exercise caution. Less than one-third of the patients said that their healthcare providers were the primary source of their information about CAM.5 Instead, patients reported that they obtained information from friends, family, the Internet, or vitamin/herbal store employees, which may or may not be reliable sources.5
Having reliable sources for information on CAM is important because the use of CAM can be dangerous. Unexpected biological interactions may occur between conventional treatments, prescribed medications, herbal and dietary supplements, and any other CAM used concurrently. Treatments may interfere or interact with each other, producing negative effects. A patient may be using a form of CAM that was effective for a fellow cancer patient, but which may cause detrimental effects in one’s own case, especially if he or she is also undergoing other cancer therapies. Physicians are often wary of recommending CAM because they have received little education and training in this area.6 Additionally, some forms of CAM have not been clinically proven safe and/or effective, leaving physicians skeptical.
With so many patients turning to CAM, our overall research objective is to investigate the use and perceptions of herbal dietary supplements, a type of CAM, among a group of female breast cancer survivors and test the effects and safety of the most commonly used herbal dietary supplements. Specifically, we propose the following questions to guide our research:
which herbal supplements do female breast cancer survivors in the D.C. metropolitan area use most? How effective do they think herbal dietary supplements are against cancer as a preventative measure, against cancer as a cure, and against cancer treatment’s side effects? How safe do they perceive herbal dietary supplements to be when used alone and when used with breast cancer treatment? How satisfied are they with herbal dietary supplements? From what sources do they receive their knowledge about herbal dietary supplements and do they think these sources are reliable? Are there correlations between the use and perceptions of herbal dietary supplements? What are the biological effects of the most commonly used herbal dietary supplements in vitro? Are these supplements safe according to in vitro studies? Are female breast cancer survivors’ use and perceptions of herbal dietary supplements in agreement with in vitro findings of the most commonly used herbal dietary supplements’ metabolic effects and safety?
In order to fulfill our objective, we plan to utilize a mixed-methods approach that combines survey and laboratory research. The survey portion of our research is designed to study the use and perceptions of herbal dietary supplements by female breast cancer survivors in the D.C. metropolitan area. The survey will inform us of the different types of herbal dietary supplements in use, survivor beliefs about these supplements, including their perceived efficacy and safety, overall satisfaction with the use of these supplements, and sources of survivor information about these supplements. By analyzing the survey, we will gain a better understanding of the general beliefs and practices of local breast cancer survivors regarding herbal dietary supplements. Based on the most common herbal supplements in use according to our early survey results, as well as the literature review and consultations with experts, we will determine which specific herbal dietary substances to study further.
Once common herbal supplements have been identified through preliminary survey findings, literature, and consultations with experts, extensive in vitro testing on these supplements will be completed in the laboratory. This work will examine the biological effects and safety of the supplements on cancer cell lines. Depending on the findings of our survey and laboratory research, we will publish and present our findings to promote awareness about the advantages and disadvantages of herbal dietary supplement use in regards to breast cancer.
Since some cancer patients are looking for treatment methods without the drawbacks of conventional treatments, our study aims to learn more about the current use of herbal dietary supplements and whether these supplements have the potential to be an effective complement to conventional treatments. More and more cancer patients are using herbal dietary supplements, but they may not be sufficiently educated about its positive and negative effects. In order to advise patients adequately, oncologists and other health professionals need more reliable information about herbal dietary supplements. In some cases, the lack of information is due to a lack of education and training; in others, it is due to a lack of research on the safety and efficacy of herbal dietary supplements. If the herbal dietary supplement that we study is shown to have potentially beneficial effects in vitro, further animal studies and perhaps clinical trials may be warranted.
In the remainder of this proposal, we provide the literature review, describe the methodology and methods, and discuss some of the limitations of the proposed research. The literature review section presents a context for our research among existing research and describes previous studies of CAM and cancer treatment. The methodology section outlines the survey and in vitro experimentation by which we will obtain data to answer the research question. Additionally, the timeline and budget are included in the appendix.
Literature Review
As we seek to address herbal dietary supplement use by cancer survivors, we must first understand how cancer is treated, how widespread it is, and what options and information survivors currently have at their disposal. Cancer treatment has evolved over the past several decades. Until the 1970s, cancer treatment principally included surgery and radiotherapy. From then onwards, there was increasing focus on cancer prevention.7 The most prevalent types of cancer today include prostrate, breast, lung, and colon and rectum cancer.8 The high frequency of cancer in the United States creates interest in cancer prevention. However, there are few new drugs for cancer prevention because they must be shown to reduce the risk of cancer and be safe for long-term administration. Currently, precancerous cells are being studied to develop new drugs that prevent cancer.9
The primary focus of Team Integrative Medicine and Cancer is breast cancer. According to the National Cancer Institute (NCI), in 2007 there were an estimated 178,480 new cases of breast cancer in women.10 A study done in 2003 showed that the number of breast cancer survivors is increasing.11 As a result, more attention and research are being directed toward the treatment of breast cancer and its symptoms and side effects. Many women are turning to CAM in order to reduce symptoms and side effects of breast cancer treatment.12 The major side effects of breast cancer treatments are menopausal symptoms, the most prevalent of which are hot flashes and nausea. Hormone replacement therapy has been found to be effective in relieving menopausal symptoms. However, there is controversial evidence of a correlation between hormone use and breast cancer recurrence or mortality.13 In 2007, alternatives to hormone replacement therapy to treat menopausal symptoms, such as tibolone, selective serotonin reuptake inhibitors, clonidine, veralipride, and gabapentin, had not yet been proven safe for that purpose.14
In the process of finding safe and effective ways to treat breast cancer and the side effects of cancer therapy, patients often consider the use of CAM. 69% of outpatients in a cancer center in the South and 50% of patients with breast cancer in the San Francisco Bay area reported using some form of CAM.15, 16 The 1999 National Health Interview Survey found that 28.9% of adults in the United States use at least one CAM modality.17 Studies suggest that CAM use is greater among cancer patients who are younger, female, have higher levels of education or income, have a history of chemotherapy or radiotherapy, who have been enrolled in clinical trials, and who have had cancer for a longer time.5, 18-21 More often than not, cancer patients use a combination of CAM modalities to treat their symptoms.22
Within the field of CAM, our research focuses on herbal dietary supplements. In general, the most commonly used supplements in the United States include Echinacea, ginseng, Gingko biloba, garlic, glucosamine, St. John’s wort, peppermint, omega fatty acids, ginger, soy, and chamomile.23 Proven to have antiproliferative and apoptotic effects in human cancer cells, chamomile also contains phytoestrogens that can decrease estrogen supply to breast cancer cells.24, 25 Several soy-derived compounds have been proven to have therapeutic effects, including genistein, an isoflavone.26, 27 Another herbal product, curcumin has a therapeutic potential in preventing breast cancer metastasis by suppressing specific gene products.28 Ginseng extract has been reported to have both wound-healing and anti-tumor effects through its effects on the vascular system.29, 30 Other herbal dietary supplements with potential anti-cancer effects include tea polyphenols, flaxseed, resveratrol, and silymarin.31-34 Our study will further explore the effects of one of these herbal supplements in combination with tamoxifen on breast cancer cells and liver cells.
As breast cancer survivors seek out these herbal therapies, the information that they receive is one of several factors that affect their decision to use them alone, use them along with conventional therapy, or use only conventional therapies. Individuals frequently obtain information about CAM from sources other than their health care providers. Specifically, it has been found that people over age 50 in the United States and gynecological cancer patients in Europe often obtain information about CAM from family and friends rather than physicians.35, 36 Cancer patients reported that their oncologists’ and specialist cancer nurses’ attitudes towards CAM affect their decisions about it.6
Another factor that affects patient perceptions of CAM is cultural beliefs. A study of Chinese cancer patients in British Columbia showed that traditional Chinese medicine was the most frequently used CAM.36 On the other hand, a study of African American prostate cancer survivors showed that prayer was the most frequent, with other forms generally viewed as superstitions.37 Cancer patients in Pakistan were most likely to use traditional herbal medicines, and frequently used CAM before seeking conventional treatments, dangerously delaying such treatment.38, 39 In addition to knowing what characteristics make people more likely to use CAM, it is important to consider why they may be using CAM. Patients use CAM for a variety of reasons; among the most common are to specifically treat cancer, to improve quality of life, and to combat treatment-related medical conditions as well as depression, anxiety, and insomnia.18, 21, 40 Our survey will further investigate the use and perceptions of dietary herbal supplements by a group of female breast cancer patients in the D.C. metropolitan area, considering issues such as information sources, culture, demographics, and medical history.
Methodology
From the information from our literature review, our team has established two methods for collecting data to answer our research question. Our methods include a survey of women diagnosed with breast cancer at least six months previously in the DC/Metro area and laboratory work with an herbal supplement to be determined through further research. Within our methodology, our team will consider the assumptions and limitations, data collection and analysis, confounding variables, and contribution to literature.
Our research consists of a mixed-method design, combining both qualitative and quantitative research.41 The qualitative data will come from a few open-ended questions in survivor surveys. The quantitative data will come from analysis of the survivor surveys and our work in the laboratory with specific herbal supplements. Using this approach will allow us to compare the use of herbal dietary supplements and how survivors perceive them (the qualitative data) to these supplements’ metabolic effects and safety in vitro (the quantitative data).
Informal interviews with oncologists will influence and inform the development of our questionnaire and the choice of which herbal supplements to study in vitro. We will speak to several oncologists within the DC/Metro area to determine the herbal dietary supplements used by their patients. We have identified and spoken with several oncologists already and currently have a subcommittee charged with continuing communication with them.
After the initial physician interviews, we will design and administer a questionnaire to breast cancer survivors who were first diagnosed at least six months prior. There are three potential sampling frames we can utilize. The first possible sampling frame will consist of female breast cancer survivors over age 18 who receive treatment at the George Washington University Medical Center over a one year period. The second potential sampling frame will consist of female breast cancer survivors over age 18 who receive treatment at the Georgetown University Medical Center over a one year period. The third possible sampling frame will consist of female breast cancer survivors over age 18 who subscribe to BreastCancer.Net News and view our advertisement on their website over a three month period, or until 400 questionnaire responses have been received. If our sampling frame is either the previously specified patients at the George Washington University Medical Center or those at the Georgetown University Medical Center, the self-administered paper-based questionnaire will be given to survivors at the hospital or an electronic questionnaire will be administered. If our sampling frame is based on subscription to BreastCancer.Net News, the questionnaire will be self-administered online. Our sample size will follow the guidelines put forth in Practical Research Planning and Design.41
The questionnaire will be pilot-tested among a small group of survivors and revised prior to administration. From the survey, we will collect quantitative and qualitative data regarding the survivors’ use of herbal dietary supplements, their perceptions of these supplements, and the sources of their knowledge of these supplements. We will analyze the information from the survey quantitatively to determine frequency of both survivor use of specific herbal dietary supplements and common information sources. These frequencies can be compared internally, within the sample, regardless of sample size. We are interested in examining potential correlations between herbal dietary supplement use, perceptions, and information sources. We will also investigate possible correlations between demographic factors and herbal dietary supplement use, perception, and information sources.