Running head: ACUPUNCTURE AND HORMONE THERAPY

Acupuncture and Hormone Therapy for Hot Flushes in Women with Breast Cancer: Critique of a Quantitative Study Hollis Misiewicz NURS 916

ACUPUNCTURE AND HORMONE THERAPY Acupuncture and Hormone Therapy for Hot Flushes in Women with Breast Cancer: Critique of a Quantitative Study

The article Long-Term Follow-up of Acupuncture and Hormone Therapy on Hot Flushes in Women with Breast Cancer: a Prospective, Randomized, Controlled Multicenter Trial by Frisk et al. (2008) describes a study that attempts to examine the effectiveness of electroacupuncture and hormone therapy in decreasing vasomotor symptoms in women who have had breast cancer. This study has an experimental design and randomized participants to receive either electro-acupuncture or hormone therapy. The purpose of this paper is to critique this research study in order to determine the quality of the findings based on an analysis of its strengths and weaknesses. Research Problem This research study addresses the problem of breast cancer survivors who experience severe vasomotor symptoms secondary to treatment-induced menopause that interfere with quality of life. This problem is clearly delineated in the introduction of the paper. It discusses the increased frequency and severity of hot flashes in the breast cancer survivor population and addresses how this interferes with daily activities, sleep and overall quality of life. The fact that the number of breast cancer survivors continues to grow based on increasing incidence of cancer and decreasing mortality is discussed and supports the significance of addressing the problem of debilitating hot flashes. This research is significant to nursing as oncology nurses support women with breast cancer deal with survivorship issues. The research study does address this problem as it attempts to determine the effectiveness of two different interventions for decreasing the severity and incidence of hot flashes in women who have had breast cancer. Research Review

ACUPUNCTURE AND HORMONE THERAPY The literature review within the body of the introduction is logically organized. The use of hormones for breast cancer survivors is cited in one study that was stopped early because of increased incidence of cancer recurrence (Holmberg & Anderson, 2004). This study was a sentinel study for the use of hormones in treating menopausal symptoms in breast cancer patients. At the time that the critiqued article was published, little research had been done using hormones for treating vasomotor symptoms because of this risk of cancer recurrence. Three

studies utilizing acupuncture for the treatment of hot flashes in breast cancer survivors are briefly summarized (Filshie, Bolton, Browne, & Ashley, 2005; Nedstrand, Wijma, Wyon, & Hammar, 2005; Porzio et al., 2002). A small quasi-experimental study by Tukmachi (2000) to evaluate the effectiveness of acupuncture for hot flashes in breast cancer survivors was not mentioned. Overall the review of acupuncture studies was fairly comprehensive at the time of this study. Gaps in the knowledge specifically addressing acupuncture for decreasing menopausal symptoms in breast cancer survivors that are identified are; (1) no evidence for long-term effectiveness of acupuncture (over 6 months) in a prospective study, (2) no research studies comparing acupuncture with sham acupuncture as a placebo, and (3) no evidence for the efficacy of acupuncture compared to hormone therapy. Theoretical/Conceptual Framework This research study does not have a clearly stated theoretical or conceptual framework. An implied conceptual framework could be the Chinese concepts of yin and yang used in acupuncture. Yin includes damp signs that point to imbalance (Kaptchuk, 2002, p. 375) and would include vasomotor symptoms. Yang is associated with heat, lightand dynamic potential (Kaptchuk, 2002, p. 375). Decreased vasomotor symptoms would be associated with yang. This study does not give a clear conceptual definition of vasomotor symptoms but does

ACUPUNCTURE AND HORMONE THERAPY make mention that they include hot flashes and sweating. As the conceptual framework is

implied it is not clearly stated what the relationship between the concepts is although it might be assumed that acupuncture would move one from the yin to the yang. Research Variables The independent variables in this study are the interventions of hormone therapy and electro-acupuncture. The treatment schedule for electro-acupuncture is clearly defined as thirty minute sessions twice a week for the first two weeks and then weekly for ten weeks. Although it states the physiotherapists were instructed about the acupuncture points, these were not specified in the article which could affect reproducibility of the study. The hormonal therapy was chosen by the participants local gynecologist. This was either sequential estrogen/progesterone if the woman had been in menopause for less than two years or continuous combined estrogen/progesterone if in menopause greater than two years. Women who had hysterectomies were on estrogen alone. It is unclear whether dosages were the same and differences here could influence internal validity. The use of tibolone was not allowed. The dependent variable was vasomotor symptoms experienced by the participants, however, what specific symptoms this encompassed was not made clear. No extraneous variables such as use of antidepressants were identified in the study. Hypotheses The purpose of the study was to determine the long-term effect of hormone therapy and electro-acupuncture on vasomotor symptoms in breast cancer survivors. There were no clearly stated hypotheses predicting what the effect on vasomotor symptoms would be or how electroacupuncture would compare to hormone therapy. The dependent and independent variables

ACUPUNCTURE AND HORMONE THERAPY stated in the purpose are testable. The conceptual framework is unclear and the purpose statement does not define a direction of effect so it is difficult to link one to the other. Sampling Women were referred for this study by breast surgeons and oncologists from three

centers in Sweden. Inclusion criteria were clearly stated to include women diagnosed with breast cancer at stage in-situ, T1 or T2 tumors with four or less positive lymph nodes, T3 tumor without metastasis, no signs of recurrence and having already completed treatment. These women needed treatment for their vasomotor symptoms as self-reported. Based on these inclusion criteria, this sample would be representative of the population to be studied and appropriate for the problem that was addressed. It is difficult to assess bias in the sample because other than reporting participants taking Tamoxifen it does not indicate whether any of the sample is taking SSRI antidepressants or other medications which can diminish vasomotor symptoms. This was not an exclusion criteria. Demographic data was similar between the two randomized groups. A power analysis was not reported and n = 45 with 27 randomized to the electro-acupuncture (EA) group and 18 randomized to receive hormonal treatment (HT). It was reported that the three centers did not fill all of their blocks and so the group sizes were skewed. At the end of the study, n = 7 for EA and n = 11 for HT. Attrition was explained but the sample size at the end made generalizability of the results questionable. Research Design The design of this study was a randomized controlled trial with participants randomized by computer to one of two interventions, hormone therapy or electro-acupuncture. The design was clearly explained and appropriate for the problem being considered. Some threats to internal validity included; (1) exclusion criteria that did not include use of medications known to

ACUPUNCTURE AND HORMONE THERAPY decrease hot flashes that would eliminate a possible extraneous variable, (2) high attrition rate partially related to the length of time the study encompassed, (3) electro-acupuncture administered by six different physiotherapists without control for manner of interaction or differences in technique other that specifying acupuncture points, and (4) differences in types of hormonal treatment and dosing that could influence response. The inclusion criteria for the study enhances external validity as the population chosen for the study is representative of that

population in general. While having different physiotherapists administer the electro-acupuncture diminishes internal validity, this actually increases external validity as it is more representative of treatment in general. Data Collection Methods Data was collected by the use of a hot flash log book where participants recorded the number of hot flashes and their distress level. These were done for one to three weeks before the start of the intervention and then continuously for twelve weeks and then one week out of every month for a total of two years. A modified version of Kuppermans Index (KI) was completed by the participant to assess menopausal symptoms at baseline and then 12 weeks and 6,9,12,18 and 24 months after the intervention started. Hot flash logs and patient rating of severity of hot flashes has been shown to be a reliable and valid tool for measuring frequency and severity of hot flashes (Sloan et al., 2001). The Kuppermans Index is widely used to assess menopausal symptoms, however, this study uses a slightly modified Kuppermans Index and its reliability and validity is unknown. The use of the hot flash log is adequately described with participants self-assessing severity and number of hot flashes. Kuppermans Index and hot flash log books were appropriate instruments for measuring the dependent variables addressed in this study. Data Analysis

ACUPUNCTURE AND HORMONE THERAPY In the text of the article the data is presented in separate paragraphs for the variables studied; (1) number of hot flashes pre 24 hours, (2) distress caused by hot flashes, and (3)

Kuppermans Index Score. Both hormone therapy and electro-acupuncture results are stated as a decrease in the median from baseline at all points of time of data collection. The results are clear and easily understood. The tables presented in the study are clearly labeled and show the mean changes in the median number in hot flash frequency for electro-acupuncture and Kuppermans Index for hormone therapy and electro-acupuncture at all points of data gathering. The level of

measurement for the variables, number of hot flashes, distress, and Kuppermans Index score are ratio measurement. Missing data were filled in using the mean of the previous and following measurement in the log books for that participant. ANOVA for repeated measures was used to analyze the differences in hot flashes and Kuppermanss Index between the two different groups and within the groups and to note trends over time. This is an appropriate statistical test for the data analyzed and for ratio measurement. Wilcoxon signed rank sum test was used and is appropriate for ordinal level data for paired comparisons within each group. Interpretation and Discussion of Findings The interpretation of the findings is mostly limited to the data concerning the use of electro-acupuncture. It does note that overall most women received some benefit from acupuncture although four women reported little effect. The authors note that in previous observations some women were resistant to acupuncture. They state that without a control group it is not possible to rule out a placebo effect although placebo effects are not usually as long lasting as changes noted in the study. The difference between findings and interpretations was made clear. Findings were not linked to any theoretical framework as the use of a framework was not specifically stated in the study. Generalizations were confined to the data presented.

ACUPUNCTURE AND HORMONE THERAPY The authors noted that small sample size and lack of a control group were weaknesses of the study. At the time of the study placebo needles had not been developed and the authors felt it would be unethical to withhold treatment to a control group. It was also noted that although hormone therapy had better results this treatment would not be a first choice as it can increase

breast cancer recurrence. The authors suggest clinicians could recommend acupuncture as a safer alternate therapy for hot flashes. The conclusion that acupuncture decreases hot flash frequency and distress is justified by the data presented although the sample size is small. Recommendations were made for future research utilizing a randomized controlled trial to compare acupuncture with placebo acupuncture in decreasing vasomotor symptoms in menopausal women. Human Subjects and Ethical Considerations This study had been approved by the Ethics Committee at the University of Linkoping and was carried out in accordance with the Declaration of Helsinki. Both written and oral information were given about the study and informed consent was obtained. It was questionable why the hormone therapy arm of the study was not discontinued following a safety analysis of the HABITS study that indicated that receiving hormonal therapy increased recurrence risk of breast cancer (Holmberg et al., 2004). The authors only recommended to participants that they stop hormone therapy and, in fact, only two women did. Conclusion Overall, the research study was well designed but sample size limited generalizability of the findings. Both HT and EA provide benefit in managing vasomotor symptoms in breast cancer patients, however, EA, is a safer alternative for oncology health care professionals to recommend to their patients.

ACUPUNCTURE AND HORMONE THERAPY References Filshie, J., Bolton, T., Browne, D., & Ashley, S. (2005). Acupuncture and self acupuncture for long term treatment of vasomotor symptoms in cancer patients -- audit and treatment algorithm. Acupuncture in Medicine, 23(4), 171-80. Retrieved from

http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=2009091609&site=ehostlive;

Frisk, J., Carlhall, S., Kallstrom, A. C., Lindh-Astrand, L., Malmstrom, A., & Hammar, M. (2008). Long-term follow-up of acupuncture and hormone therapy on hot flushes in women with breast cancer: A prospective, randomized, controlled multicenter trial. Climacteric : The Journal of the International Menopause Society, 11(2), 166-174. doi:10.1080/13697130801958709

Holmberg, L., Anderson, H., & HABITS steering and data monitoring committees. (2004). HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: Trial stopped. Lancet, 363(9407), 453-455. doi:10.1016/S01406736(04)15493-7

Kaptchuk, T. J. (2002). Acupuncture: Theory, efficacy, and practice. Annals of Internal Medicine, 136(5), 374-383.

Nedstrand, E., Wijma, K., Wyon, Y., & Hammar, M. (2005). Vasomotor symptoms decrease in women with breast cancer randomized to treatment with applied relaxation or electroacupuncture: A preliminary study. Climacteric : The Journal of the International Menopause Society, 8(3), 243-250. doi:10.1080/13697130500118050

ACUPUNCTURE AND HORMONE THERAPY Porzio, G., Trapasso, T., Martelli, S., Sallusti, E., Piccone, C., Mattei, A., Marchetti, P. (2002).

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Acupuncture in the treatment of menopause-related symptoms in women taking tamoxifen. Tumori, 88(2), 128-130.

Sloan, J. A., Loprinzi, C. L., Novotny, P. J., Barton, D. L., Lavasseur, B. I., & Windschitl, H. (2001). Methodologic lessons learned from hot flash studies. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 19(23), 4280-4290.

Tukmachi, E. (2000). Treatment of hot flushes in breast cancer patients with acupuncture. Acupuncture in Medicine, 18(1), 22-7 (43 ref). Retrieved from http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=2000073260&site=ehostlive;