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This study aims to identify non-genetic factors that increase or decrease breast cancer risk in twins. This information could help researchers identify ways to help prevent breast cancer from occurring.
In any population, with the presence of more than 100 genetic determinants, most breast cancer cases are likely to carry one, yet community occurrence is dominated by non-genetic risk factors. Adult identical twin women are representative of the population of origin in both genetic and non-genetic factors. However, when one gets breast cancer, the lifetime risk to the co-twin is much higher than expected on the basis of risk to an ordinary sister. Even so, only about a quarter of such co-twins become affected, and those that are become diagnosed years later. Thus affected pairs, whether breast cancer discordant or concordant, differ in the level of penetrance, and since the genetic determinants carried by concordant cases are unlikely to differ from those in discordant cases, the difference between such affected pairs, given the same genetic determinants, also reflects a different level of penetrance. We propose to verify the identity of genetic determinants between discordant and concordant pairs (using the Illumina OncoArray 500K), and to document the existence and timing of exogenous determinants of higher penetrance. This will be within discordant pairs, between the members of concordant pairs differing in age at diagnosis, and between cases from discordant and concordant pairs with the same or similar genotype. We will use adult twins’ documented ability to accurately recall childhood differences between themselves in behaviors, environmental exposures, and given current emphasis on adolescence, the rate of development.
This study is designed to identify both signs and symptoms of breast cancer-related lymphedema and genetic factors that predict whether patients are at increased risk for developing lymphedema. The researchers intend to use the results to develop and test new approaches to prevent or reduce the risk of lymphedema developing following breast cancer treatment.
Chemotherapy-Induced Neuropathy in Cancer Survivors
Lymphedema (LE) following treatment for breast cancer is the most common form of secondary LE in the industrialized world. It occurs in 20% to 87% of patients following treatment for breast cancer and results in significant disability. At the present time, the definitive phenotypic, genotypic and epigenotypic predictors that place patients at highest risk for the development of LE are not known. Therefore, the specific aims of this study, in a sample of patients following treatment for breast cancer, are to: determine genetic predictors of LE using a candidate gene approach and evaluate for epigenetic changes, as measured by DNA methylation and subsequent gene expression, in candidate genes associated with the diagnosis of LE. The secondary aims of this study are to: evaluate for latent classes of women with distinct phenotypic predictors of LE; and evaluate for differences in symptoms, functional status, and QOL outcomes between women with and without LE and among the latent classes with LE. The results of this study will provide new information on the underlying mechanisms for LE and allow for the development and testing of novel approaches to prevent or reduce the negative effects of LE.
Genetic and non-genetic factors are believed to influence whether a woman with a BRCA1, BRCA2, and/or PALB2 mutation goes on to develop breast and/or ovarian cancer. The study is trying to identify which hormonal, reproductive, and lifestyle factors may increase cancer risk in this high-risk group.
The risk of breast cancer has been estimated to be up to 87% lifetime for women with a BRCA1 or BRCA2 mutation. Genetic testing is now established throughout Canada with the goal of preventing breast cancer in high risk women. The risks of breast and ovarian cancer in BRCA1 and BRCA2 carriers vary from woman to woman, based on age, family history, reproductive history and preventive surgeries. Preventive salpingo-oophorectomy reduces ovarian cancer risk by 80% and breast cancer risk by 50%. However, there is great interest in alternatives to surgery and in means of further reducing the risk of breast cancer after oophorectomy. Tamoxifen is approved for cancer prevention for pre- and post-menopausal women. Much evidence shows that tamoxifen can be used to prevent contralateral breast cancer in BRCA1 and BRCA2 carriers, but there is no direct evidence yet to support its use for primary prevention in BRCA mutation carriers and many women are reluctant to take it. We have recently shown, in a case-control study, that one year of tamoxifen reduces contralateral cancer in BRCA1 and BRCA2 carriers by up to 70%. It is important to establish the beneficial effect of tamoxifen chemoprevention on primary cancer risk in a large prospective study and to compare the risk reduction obtained with that of preventive mastectomy and oophorectomy.
1. To estimate the hazard ratio for first primary breast cancer associated with use of one or more years of preventive tamoxifen in women with a BRCA1 or BRCA2 mutation.
2. To compare the lifetime risks of breast cancer in carrier women who take tamoxifen with those who undergo preventive mastectomy or oophorectomy.
3. To create a user-friendly web-based interface for women with a BRCA1 or BRCA2 mutation to allow them to estimate their personal risks of breast and ovarian cancer and to estimate the expected impacts of tamoxifen and of preventive surgeries on breast and ovarian cancer risk.
The purpose of this study is to investigate the relationship between your cardiovascular fitness and your body’s immune response, as both may be related to fatigue (tiredness), mood, pain sensitivity, memory, and concentration—known side effects of cancer and its treatments. By learning if people with better cardiovascular fitness have lower inflammation, researchers will be able to discover whether and how regular exercise benefits breast cancer survivors.
This double-blind, randomized, crossover trial will evaluate inflammatory and behavioral responses to typhoid and placebo inoculations as a function of cardiorespiratory fitness, age, and depression in breast cancer survivors. The aims of the project are (1) to evaluate the relationships between cardiorespiratory fitness and inflammatory and behavioral responses (negative mood, fatigue, pain, and cognitive problems) to typhoid vaccine; (2) to determine the effects of age and depressive symptoms on inflammatory and behavioral responses to typhoid vaccine and placebo; and (3) to assess the ability of cardiorespiratory fitness to moderate age- and depression-related responses to typhoid vaccine. These questions are important because inflammation, a robust and reliable predictor of all-cause mortality in older adults, is one of the key candidate mechanisms for age-related decrements in physical function and disability. Individuals frequently encounter immune challenges in daily life, and the ability to minimize inflammatory responsiveness influences the total burden that infectious challenges or tissue injury place on an individual. Larger, more frequent, or more persistent inflammatory changes have negative consequences for health. If better cardiorespiratory fitness dampens or limits inflammatory responsiveness, then this study could demonstrate a new and novel mechanism through which regular exercise produces its substantial health benefits.
The purpose of this study is to see whether neratinib is effective in treating HER2-negative metastatic tumors that have this specific HER2 mutation. The first part of the study is a preliminary screening. During this part of the study, your tumor tissue will be tested to see if it has the HER2 mutation the researchers are looking for. If your tumor has the mutation, you will be given more information about the main research study, which is investigating the effectiveness of neratinib.
The research team proposes to conduct a single arm 2-stage Phase 2 trial of neratinib in metastatic but HER2 non-amplified but HER2 mutant breast cancer. Pre-registration is required for tumor HER2 sequencing. The primary objective is clinical benefit rate (CBR: rate of complete response plus partial response and stable disease > 6 months). With an 80% power and a 1-sided 0.05 significance level, the first stage of 10 patients and the 2nd stage of 19 patients are planned to test an anticipated CBR of 20% versus the null hypothesis of 5%. Secondary endpoints include progression free survival and the molecular epidemiology of HER2 mutation. Exploratory endpoints include mechanisms of treatment resistance and other somatic mutations in HER2 negative disease. Because the mutation frequency is approximately 2%, they anticipate screening of 1500 patients to identify the 29 patients with the HER2 mutation and eligible for study drug therapy. The success of this trial could establish a new treatment option for a subset of patients with HER2 non-amplified tumors.