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1 Dana-Farber Cancer Institute, Boston, Massachusetts and 2 Catalan Health Department, Catalonia, Spain
Requests for reprints: Lisa M. DiGianni, Dana-Farber Cancer Institute, 44 Binney Street, SM228, Boston, MA 02115. Phone: 617-632-5429; Fax: 617-632-3161. E-mail: lisa_digianni{at}dfci.harvard.edu
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Abstract |
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Methods: A cohort of 243 high-risk women completed questionnaires at enrollment into a BRCA1/2 randomized trial and 1 year post results disclosure. Uses of several CAMs for cancer prevention were explored, including ingestible, behavioral, and physical modalities. Assessment of the change in CAM use from baseline to 1 year follow-up was conducted using a repeated self-administered questionnaire. Correlates of the number of CAMs used at 1 year were explored using multivariable linear regression models.
Results: Among the subset of women who changed their CAM behavior from enrollment to 1 year following BRCA1/2 results disclosure, there was a significantly higher proportion who changed from no CAM use to CAM use among the overall cohort (P = 0.01), among women without cancer at enrollment (P = 0.003), among women found to be BRCA1/2 carriers (P = 0.03), and among women randomized to the genetic counseling intervention arm of the study (P = 0.009). Number of CAMs used at 1 year was positively associated with number of CAMs used at baseline, sunscreen use, and BRCA1/2 mutation status.
Conclusion: High-risk women who have received BRCA1/2 counseling and testing frequently adopt new CAM use in the first year after learning their genetic status. Mutation carriers frequently initiate CAM use after learning their genetic status as part of their cancer preventive regimen. Further studies are warranted to determine the efficacy of CAM-related strategies for cancer prevention. (Cancer Epidemiol Biomarkers Prev 2006;15(1):70–5)
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Introduction |
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High-risk women undergoing BRCA1/2 testing face the possibility of confronting difficult health maintenance decisions (11). Women who test mutation positive must consider, for example, when or whether to undergo prophylactic mastectomy and/or oophorectomy (12). In an earlier study, we found that 50% of our cohort of high-risk women used CAM as part of their on-going health maintenance program (13). In this study, we sought to explore the types of CAM high-risk women use for cancer prevention following receipt of BRCA1/2 genetic test results, as well as whether women alter their CAM-related practices in the year following genetic testing. In addition, we assessed the association between number of CAMs used at 1 year follow-up with use of other health behaviors, as well as any relationship between CAM use and distress, breast cancer risk perception, and BRCA1/2 mutation status.
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Materials and Methods |
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Participants were required to meet the following eligibility criteria: (a) female; (b) age 18 years or older; (c) personal or family history of breast, ovarian, or other cancer consistent with BRCA1/2 heredity with posterior probability of carrying an altered gene of 
10% based on published probabilities and Bayesian calculations; and (d) documentation of participant or family member cancer diagnosis. Individuals who met the eligibility criteria were mailed an enrollment packet, which contained the baseline questionnaire, informed consent, medical insurance information form, and project brochure. On receipt of the completed enrollment packet materials at the study center at the Dana-Farber Cancer Institute, project staff enrolled and randomized each participant to receive either formal genetic counseling conducted by a genetic counselor or an enhanced consent intervention administered by a medical oncology nurse. (A comprehensive comparison of the two interventions will be reported separately.) Participants were required to attend two visits at their study site, and received their BRCA1/2 test result during their second appointment. Structured standardized interview guides were designed for both the genetic counseling and enhanced consent arms of our study. The genetic counseling intervention was designed as a client-centered model, a psychological approach in which the use of scenario-based decision counseling taught as part of genetic counseling masters degree programs was encouraged. The enhanced consent intervention was adapted from the medical model of informed consent, in which oncology nurses reviewed the informed consent document section by section, soliciting questions after each. No specific discussion or recommendations regarding any aspect of CAM use were included in the structured components of the genetic counselor, nurse, or physician sessions. Women were followed for 1 year after receiving their genetic test results. A federal Certificate of Confidentiality was obtained to prevent undesired disclosure of personal information. The Institutional Review Board at the Dana-Farber Cancer Institute and participating institutions approved this study.
Measures
Demographic information, including cancer history, was collected from all interested study participants before the mailing of the enrollment packet. Completion of the enrollment questionnaire was required for entry into the program; therefore, the response rate for this survey is 100% of program enrollees. Questionnaires were also completed 1 year following results disclosure by 83% of the sample. The enrollment, 1 year follow-up, and demographic instruments provide the data sources for this paper.
Complementary Medicine Use. To assess CAM use at baseline enrollment into the program and 1 year following genetic testing, participants were asked, "Which of the following complementary therapies have you used to prevent cancer?" We derived a modified list from early CAM instruments designed by Eisenberg et al. (1) and Richardson et al. (8), consisting of vitamins, special diet/nutrition, herbal remedies, exercise, meditation/yoga, massage therapy, energy work (i.e., polarity, reiki), and acupuncture/acupressure. To compare overall change in CAM use from baseline enrollment to 1 year follow-up, participants were classified as using "any CAM" if they reported using at least one therapy of the eight modalities specifically for cancer prevention. Two additive scales of the number of CAMs used at enrollment and 1 year were also created (range 0-8) to assess association between participant characteristics and number of CAMs used at 1 year. Relationship of the covariates to individual CAMs was also explored.
Patient Characteristics. Standard demographic and health history information was obtained and dichotomized for this analysis: cancer history (cancer versus unaffected), age (46 years or less versus older than 46 years), education (less than college versus college or more), ethnic derivation (Ashkenazi versus non-Ashkenazi Jewish), annual household income (<$65,000 versus $65,000 or more), and randomization intervention (genetic counseling versus oncology nurse consent).
BRCA1/2 Mutation Status. BRCA1/2 test results were classified as positive, true negative (negative test for a documented familial mutation), uninformative negative (negative test in the absence of a documented familial mutation), and genetic variant of uncertain significance. Because most variants have been shown to have no functional significance, for the purposes of this analysis, genetic test results were dichotomized into "positive" versus "other."
Cancer-Related Health Practices. Health surveillance behaviors may have an influence on cancer outcome and may be related to CAM use (13, 14). Participants were asked several questions regarding their cancer-related health behaviors 1 year following disclosure. The following items were selected for this analysis due to the variability of these behaviors among this sample—"How many clinical breast exams (CBE) have you had in the last 12 months?" Responses to this item ranged from 0 to 2 or more—with two or more indicating medical adherence for women with high breast cancer risk. "Do you see a dermatologist annually for skin exams or to have moles screened for signs of cancer?" Responses were coded as "yes at least once per year;" "yes less often than once per year;" "only when I have a problem;" or "no." "Do you typically wear sunscreen with an SPF of 15 or more when you are in the summer sun for >15 minutes (15)?" Responses were coded as "always," "often," "sometimes," "rarely," and "never." Alcohol and cigarette use were explored in preliminary analysis, however, not included in final analysis due to low prevalence of these behaviors among our sample. Participants were not asked about their frequency of obtaining pap tests or colorectal cancer screening.
Anxiety/Depression. We and others have reported a preliminary relationship between increased depression and CAM use (13, 16). To further explore this association, we used the standardized depression and anxiety subscales of the 53-item Brief Symptom Inventory (17). Participants were asked about their emotional well being in the past 7 days, with response categories on a 5-point Likert scale. Several standardized subscales were calculated, including indices of anxiety and depression, which were dichotomized at the sample medians into "lower anxiety score" and "higher anxiety score" and "lower depression score" and "higher depression score."
Risk Perception. Our cohort was asked to provide a numerical response to the following item separately for breast and ovarian cancer: "On a scale from 0% to 100%, where 0% is no chance at all and 100% is absolutely certain, what do you think are the chances that you will develop (another) breast/ovarian cancer at some point in your lifetime?" For the purposes of this analysis, responses were dichotomized at each of the sample medians for breast and ovarian cancer.
Statistical Analysis
Statistical analyses were conducted using SAS software (18). Participant characteristics comparing CAM users and nonusers were explored using cross-tabular analysis and Fisher's exact tests (19). Cross-tabular comparison of change in CAM use from baseline to 1 year follow-up was made using McNemar's test, which analyzes for change in proportion between two samples (19). All P values reported were two-tailed, with a level of P < 0.05 to determine statistical significance. Covariates with a P < 0.20 in preliminary univariable regression analysis were entered into multivariable linear regression models to explore their relationship with number of CAMs used at 1 year for cancer prevention. The stepwise method was used for variable selection. Randomization assignment was controlled for in all analyses. Cancer survivors and unaffected participants were analyzed separately for all analyses. Exploratory analysis was conducted to investigate the correlation between the individual CAMs and selected covariates. The fact that the large majority of families (n = 271) had only one participant precluded the use of generalized linear models to control for any potential effects of having some families with more than one participant.
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Results |
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Discussion |
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Women at high genetic risk tend to practice better health behaviors than average-risk women (11). This pattern was reflected in our cohort—only 3% reported that they currently smoked, whereas 54% regularly engaged in strenuous exercise, such as running, swimming, or aerobics, and 71% consistently protected themselves while in the sun. U.S. general population data on women report higher smoking rates (21%; 22), less regular physical activity (40%; 23), and less regular sunscreen use (33%; 24) than our high-risk women. Lifestyle incorporation of cancer prevention health practices after genetic testing is further reflected in our cohort with unaffected women, mutation carriers, and recipients of the genetic counseling intervention significantly reporting new CAM use 1 year following genetic testing. Although standardized interview guides were used for women randomized to both study arms, the genetic counseling intervention was structured as the more client-centered, psychological approach. Although the interview guides were not specifically designed to elicit discussion of CAM, it is plausible that this topic may have arisen as an area of interest during discussion of cancer-related lifestyle choices. Our findings indicate that high-risk women might undergo health behavior changes after receiving genetic test results. This may be an important moment in which to influence modifiable health practices, particularly in pursuit of healthier lifestyles.
Some studies have shown that modifiable behaviors, such as physical activity, diet, and body mass index, may be associated with breast cancer risk for high-risk women. King et al. (25) documented a significant relationship between increased physical activity, lack of obesity, and decreased breast cancer risk for women with BRCA1/2 mutations. Carpenter et al. (26) explored the effect of family history, exercise, and obesity on postmenopausal breast cancer risk, and found that breast cancer risk significantly increased with higher body mass index levels for women with a strong family history. Although it was previously thought that certain diets, such as those higher in soy and other phytoestrogens, might decrease breast cancer risk, those relationships remain unclear (27). Further, several studies have concluded that soy-related products might not be beneficial in reducing hot flashes for menopausal or postmenopausal breast cancer survivors (28-30). However, it is noteworthy that Fung et al. (31) did report a significant relationship between higher consumption of fruits and vegetables and a decreased risk for estrogen receptor–negative breast cancer.
BRCA1/2 mutation carriers are typically faced with making unique health care decisions for cancer risk management (12). Some high-risk women may elect chemoprevention or prophylactic surgical options and might also include regular practices, such as mammography, breast MRI, or breast ultrasound, as part of their cancer screening regimens (32). Meijers-Heijober et al. (33) reported that 55% of mutation carriers from their program in the Netherlands underwent a prophylactic mastectomy and 60% had a prophylactic oophorectomy within 2 years after genetic testing. In contrast, Lerman et al. (12, 34) found that many BRCA1/2 carriers opted not to undergo prophylactic surgery in spite of their increased cancer risk. Botkin et al. (34) documented few prophylactic mastectomies in their cohort of mutation carriers; however, 46% of carriers had undergone a prophylactic oophorectomy by 2 years postdisclosure. Whereas it is possible that our study was not significantly powered to detect an effect, we did not find any relationship between choosing prophylactic surgery and CAM use at 1 year follow-up for unaffected mutation carriers. The association in our data between other cancer-related health choices and CAM indicates that healthy high-risk women may elect to optimize cancer risk management options other than prophylactic surgery to minimize mutation-associated cancer risk.
Cancer risk behavioral decisions made by high-risk women are clearly complex and multifaceted. However, healthy nutrition and exercise guidelines for women at high cancer risk, as well as for the general population, have become standard (35). Lovegrove et al. (36) explored factors that may be important in cancer-related behavioral decisions made by high-risk women. The authors found that half of their cohort who had overestimated their cancer risk and who declined participation in a chemoprevention trial were significantly more aware of traditional lifestyle factors thought to play a role in cancer risk reduction, including diet and exercise, than those who enrolled in the trial. In our study, we were puzzled by the negative correlation between CAM use and risk perception and CAM use and annual CBEs for unaffected women. To further investigate these findings, we separated the eight-item CAM scale into individual CAMs, which allowed us to explore the relationship of the covariates with the more traditional health behaviors—exercise, nutrition, and diet—separately from the more alternative approaches, including massage and energy healing. Although we did not have sufficient power to detect strong differences, the negative association between risk perception and the more traditional health behaviors did not persist, but it was maintained for more alternative activities. Perhaps women with higher-risk perception may be so apprehensive about their cancer risk that they are not willing to experiment with newer approaches and may be more comfortable with strategies such as vitamins, nutrition, and exercise, which have been associated with cancer risk reduction. Similarly, it is possible that women who maintain more frequent cancer surveillance practices, such as obtaining two or more annual CBEs, are more interested in more established CAM modalities. These observations merit further investigation.
Depression and anxiety have been found to affect health behavior choices made by women with high cancer risk (37). CAM use may help reduce stress in individuals facing chronic diseases (3, 38). In our earlier study, we reported an association between higher levels of depression and CAM use for cancer survivors at baseline entry into our BRCA1/2 testing program (13). Our current follow-up data do not reflect a relationship between depression and CAM use for either cancer survivors or unaffected women. However, we did find an association between anxiety and CAM for unaffected women at 1 year follow-up, indicating that healthy women may seek CAM as one strategy to help manage stressful issues arising from receiving genetic testing information.
Some limitations to our study should be noted. First, previous studies have shown that socioeconomic status is significantly correlated with CAM use (3, 5, 6). The majority of our cohort had high educational and annual income levels, as has been typical for many studies of women receiving BRCA1/2 testing, limiting the generalizability of our findings (39). Second, our study instruments were designed in 1998 when CAM research was emergent. Thus, our CAM categories—although based on the best available data at the time—provided us with limited detail on the types of CAM used. For example, it would have been helpful to know the types of exercise, special diets, and vitamins used by our cohort for cancer prevention. Additionally, our cohort was not asked items that have become increasingly relevant in the exploration of CAM use, including when CAM use began or motivations for using CAM. This information would have been particularly helpful in interpreting our results, especially with regard to whether cancer survivors began using CAM before or after their cancer diagnosis. It should be noted that with regard to cancer survivors, we did explore the relationship between CAM use and length of time since cancer diagnosis (<5 years ago versus 5 years or more), and CAM use and age at cancer diagnosis (younger than age 46 years versus age 46 years or older); we did not find a relationship between these items. Further, we would have explored predictors of CAM use ideally by creating a high-risk breast management guideline adherence scale. However, we felt that this was not feasible based on our available data. At the time our study was designed, breast-imaging techniques were not yet routinely recommended for high-risk women as reflected in our data (conducted regular breast MRI and breast ultrasound 4%, respectively). Mammography adherence also became difficult to explore due to the fact that 40 women in our cohort had no breasts remaining by 1 year postdisclosure. To delete this group from the analysis would have resulted in significant loss of sample size. We opted instead to focus on CBE as an indicator of breast management adherence due to the fact that there was sufficient variability in this item to explore its relationship to CAM use. Finally, due to the lack of association between CAM use and ovarian cancer risk perception in our data, we were unable to fully explore the effect of CAM use on ovarian cancer risk management specifically. This remains an area needing further exploration.
Although there is minimal scientific information on the true role of CAM-related approaches in cancer prevention (40), our study indicates that high-risk women may adopt new CAM behaviors following genetic testing. As high-risk women consider their nonsurgical cancer risk reduction options, such as increased physical activity, healthy body weight, and other behavioral strategies, providers may consider encouraging women to participate in related chemoprevention trials. Providers should be aware that high-risk women may already be using CAM-related behaviors when reviewing their approaches for coping with their cancer risk and should be prepared to address available data on the advisability or inadvisability of these practices. Further, randomized nutrition and physical intervention studies for high-risk women are warranted to assist in determining the actual effectiveness of these strategies for cancer risk reduction.
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Acknowledgments |
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Footnotes |
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: This is an original report presented at the American Society of Clinical Oncology Annual Meeting June 2004.
Received 8/18/05; revised 10/14/05; accepted 11/ 7/05.
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