Breast cancer remains one of the most prevalent forms of cancer in humans. According to the American Cancer Society, an estimated 230,000 cases of breast cancer had to occur in 2011. Between 1999 and 2005, incidence and prevalence rates for breast cancer decreased by approximately 2% per year (American Cancer Society, 2011). The dramatic decline in breast cancer incidence was attributed to the significant reductions in the use of hormone replacement therapy among menopausal and post-menopausal women (American Cancer Society, 2011). The public health emphasis is shifting from treatment toward prevention. As a result, breast cancer prevention is becoming one of the major public health priorities. It comes as no surprise that vaccination against breast cancer has become a popular object of epidemiological analysis. Back in 1990, Hareuveni et al. tested vaccination against tumor cells expressing an epithelial tumor antigen (ETA) and discovered that “vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S” (p.9498). Later in 2001, Gilewski et al. reported the results of vaccinating breast cancer patients with a well-pronounced synthetic globo H conjugate. Eventually, Disis et al. (2009) explored the effects of concurrent trastuzumab and HER2/neu-specific vaccination and found that, with minimal toxicity involved, the proposed combination resulted in robust and prolonged immune responses in patients. Despite the growing body of literature, the long-term effects of vaccination on breast cancer risks are poorly understood. Thus, the main research question is the prolonged effects of vaccination/immunization on breast cancer risks and survival in women.
Experimental/Clinical Trial
The idea and design of this clinical trial are borrowed from Disis et al. (2009). The objective of the study is to test the effects of HERs/neu-specific vaccine on patients with non-metastatic breast cancer. The essence of the experiment is to compare the effects of vaccination on members of the experimental group to those in the control group (Rosenberger & Lachin, 2002).
All patients involved in the clinical trial must meet several important criteria. First, all patients are women with stage III-VI breast cancer. Second, all patients are in the state of complete remission. Third, and according to Disis et al. (2009), all patients must have a documented overexpression of HER2/neu. The sample size is determined, so that the probability of allergenic and toxic reactions to vaccination does not exceed 10% (power 0.90). For the purpose of statistical analysis, the confidence interval is determined at 0.95, and the significance threshold is 0.05. The procedure involves measuring changes in serum and peripheral-blood mononuclear cells (Disis et al., 2009). Paired t-tests and two-tailed Mann-Whitney tests are used to measure possible variations in the immune reactions across the experimental and control groups.
Clinical trials are associated with considerable risks of bias and error. At the stage of recruitment/ enrollment, failure to meet the eligibility requirements may lead to biased results (Rosenberger & Lachin, 2002). For example, if not all study participants are in the state of complete remission, the effects of and reactions to immunization may be misleading. It is imperative that all patients enter the trial simultaneously and do not violate the protocol requirements. Difficulties with determining the sample size cannot be easily dismissed. The duration of the trial is of vital importance for the quality of the study results. The duration of the trial should ensure that the experiment meets the predetermined objective and, if possible, mimics usual clinical practices (Rosenberger & Lachin, 2002). Finally, the quality of clinical trial results directly depends upon patient compliance. In the discussed case, all subjects are required to complete five immunizations; those who fail to complete all immunizations are automatically excluded from the study sample. The results will be considered positive if vaccination generates sustained immune responses in the study participants.
Cohort Study
Retrospective cohort studies are designed to explore and analyze past exposures and their effects on the target population. This retrospective cohort study will explore the relationship between vaccination and breast cancer risks in women. The proposed research is a nonintervention cohort study, which analyzes past records and experiences, to define whether vaccination reduces the risks of breast cancer in women. The main enrollment criterion is the absence of the history of breast cancer at the time of vaccination. Clinical follow-up entails blood and physical examinations; no biopsy specimens are to be taken, not to interfere with the course of disease (if the disease develops). The retrospective cohort is divided into an exposed (vaccinated) and non-exposed (non-vaccinated) groups. With the help of statistical analysis, the relationship between vaccination and survival is traced; the number of patients who achieve the end of the follow-up procedure is measured. The statistical proportional analysis involves the use of chi-square. Based on the study by Gruijl et al. (1997), 95% confidence intervals, odds ratios and chi values are calculated. The results are considered significant when P<0.05.
The risks of error and bias are numerous. First, the accuracy and completeness of the information on past exposures influence the quality and validity of retrospective cohort study results. The researcher cannot guarantee that (a) patients provide accurate information about their health and past health problems and (b) the necessary information on breast cancer and vaccinations was recorded timely and accurately (Killewo, Heggenhougen & Quah, 2010). Second, not all patients can be traced fully, to establish whether or not they develop breast cancer and how many of them eventually die (Killewo et al., 2010). Third, the researcher may not be able to obtain the fullest and accurate information on the characteristics and problems of the study participants, which are not directly related to the outcome of interest but can be potentially useful (Killewo et al., 2010). Without this information, the interpretation and analysis of study results will be inherently biased. Finally, and in terms of the non-exposed (non-vaccinated) group, differences in the nature and quality of vaccination preparations may interfere with the study results. Nonetheless, the researcher expects that the cohort study will help to determine the nature of the relationship between vaccination and breast cancer risks, as well as the potential effects of vaccination on breast cancer survival among women.
Case Control Study
Case control study designs are common in epidemiological research (Schulz & Grimes, 2002). Epidemiologists can use case control study designs to analyze associations between vaccination and breast cancer survival and risks. Case control studies always involve participants with and without the target disease (Killewo et al., 2010). This case control study will measure and compare the effects of vaccination on breast cancer risks. The case control group involves women with the stage I breast cancer diagnosed within two months prior to the study; the control group includes women without breast cancer. All women fill out a written interview form specifying their health, family, and environmental history. Women in the case control group must have at least one completed pregnancy and no history of chemotherapy. Control participants are recruited through random digit dialing (Killewo et al., 2010). The presence or absence of breast cancer vaccination is the basic measure of analysis. Logistic regressions are used to measure the association between vaccination and the disease status, further adjusted for a range of confounding factors (age, ethnicity, family history of cancer, etc.).
The following risks of bias and error have to be considered. To begin with, the researcher may not be able to access and obtain the fullest information on the target and other, related and non-related risk factors (Killewo et al., 2010). Furthermore, it is never possible to consider all confounding factors. Research participants may not be able to reveal and disclose relevant health information, and the comparability of results obtained in the case and control groups will decrease (Killewo et al., 2010). Third, case control studies provide little information on causality of the exposure; the researcher may fail to determine whether the non-vaccinated status of respondents is the main predictor of breast cancer or whether women at high risk of developing breast cancer refrain from obtaining vaccination for other, subjective reasons. Eventually, difficulties with arranging a control group present a serious threat to the validity and reliability of the study findings. Selection of the control group must be independent from the exposure (Schulz & Grimes, 2002). Actually, the choice of the control group in case control studies is one of the most difficult in epidemiology (Schulz & Grimes, 2002). The researcher expects that the study will allow evaluating the relationship (if any) between vaccination and breast cancer. The study will facilitate the analysis of other confounding factors and their contribution to breast cancer risks.
Cross-Sectional Study
Cross-sectional studies are designed to measure “both the exposure to a hypothesized risk factor and the occurrence of a disease at one time” (Killewo et al., 2010, p.66). The purpose of this cross-sectional study is to measure the relationship between breast cancer risks and vaccination. The questions to be answered in this study include:
does vaccination reduce the risks of breast cancer in women?;
is women’s willingness to search vaccination associated with the fear of developing breast cancer or their exposure to breast cancer risks (namely, family history of breast cancer)?;
what psychological, cognitive, and social factors contribute to women’s desire to obtain vaccination?
The sample will include women with III-IV stage breast cancer in the state of complete remission, who have completed their medical treatment at least one year prior to the study. The study sample includes only postmenopausal women aged 50 and older. The cross-sectional factors to be considered in the study include family history of breast cancer, self-esteem, socioeconomic status, and the fear of developing breast cancer. SPSS will be used to measure statistical correlations between these factors. Chi-square and t-tests will help to examine the contribution of these factors to the development of breast cancer.
The risks inherent in cross-sectional studies are mostly similar to those involved in other study designs. Enrollment, compliance, and the accuracy of information provided have to be taken into account. Cross-sectional studies usually involve old and new cases of the disease, but the diagnostic criteria of breast cancer may change, the researcher will find it difficult to compare the results of epidemiological analysis across the old and newly diagnosed subjects (Killewo et al., 2010). The results of the study will help to create a more objective picture of the breast cancer-vaccination relationship. The researcher will be able to evaluate the contribution of various objective and subjective factors to women’s willingness to obtain breast cancer vaccination.
References
American Cancer Society. (2011). Cancer facts & figures. The American Cancer Society. Web.
Disis, M.L., Wallace, D.R., Gooley, T.A., Dang, Y., Slota, M., Lu, H. (…) & Salazar, L.G. (2009). Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. Journal of Clinical Oncology, 27(28), 4685-4692.
Gilewski, T., Ragupathi, G., Bhuta, S., Williams, L.J., Musselli, C., Zhang, X.F. (…) & Danishefsky, S.J. (2001). Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial. PNAS, 98(6), 3270-3275.
Gruijl, T.D., Bontkes, H.J., Walboomers, J.M., Schiller, J.T., Stukart, M.J., Groot (…) & Scheper, R.J. (1997). Immunoglobulin G responses against human Papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia. Journal of National Cancer Institute, 89, 630-638.
Hareuveni, M., Gautier, C., Kieny, M.P., Wreschner, D., Chambon, P. & Lathe, R. (1990). Vaccination against tumor cells expressing breast cancer epithelial tumor antigen. Proceedings of the National Academy of Science, 87, 9498-9502.
Killewo, J., Heggenhougen, K. & Quah, S.R. (2010). Epidemiology and demography in public health. Academic Press.
Rosenberger, W.F. & Lachin, J.M. (2002). Randomization in clinical trials: Theory and practice. John Wiley and Sons.
Schulz, K.F. & Grimes, D.A. (2002). Case-control studies: Research in reverse. Lancet, 359, 431-434.