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The purpose of this study is to learn how two different medications affect the breast: an estrogen-free selective progesterone-receptor modulator called UPA vs. a low-dose oral contraceptive pill. This is a randomized, phase I clinical trial. Participants have a 50% chance of receiving the UPA pill, and 50% chance of receiving the low-dose oral contraceptive.ve.
Breast cancer accounts for almost a quarter of all cancers in women. It is estimated that in the U.S. in 2014 more than 230,000 women were diagnosed with the disease and 40,000 died of the disease. Tamoxifen is an effective chemopreventive agent; however, it is not widely used, in part due to its increased risks of endometrial cancer and venous thromboembolism. The United States Preventive Services Task Force recommends tamoxifen use only for those at high risk of breast cancer. There is an urgent need to develop acceptable means of preventing the disease both for high risk and average risk women.
The proposed study is a clinical trial in premenopausal women aged 18-40 to evaluate the capacity of daily Ulipristal Acetate (UPA) to reduce breast epithelial cell proliferation and to measure its effect compared to that found with a combined estrogen-progestin oral contraceptive (COC). UPA is a selective progesterone receptor modulator (SPRM) in use as daily medication up to 12 months for the treatment of menorrhagia due to uterine fibroids, and is currently in trials in the U.S. to evaluate its use as a daily contraceptive. The proposed study will allow us to investigate the potential of UPA to reduce breast cell proliferation and possibly breast cancer risk if used over an extended period of time.
We will compare breast cell proliferation, as measured by Ki67 expression in breast biopsies, at the end of 3 months treatment to baseline values in the 2 groups (UPA and COC). We will also compare the changes in the 2 groups to each other. The comparison of the effect of UPA to that of a conventional COC is because of UPA’s potential use as a daily contraceptive.
Cell proliferation in the breast occurs throughout the menstrual cycle and is roughly twice as high in the luteal phase (elevated progesterone phase) of the cycle. The actions of hormones on the breast are rapid and an anti-progestin such as UPA, which will block the action of progesterone in the breast would be predicted to quickly lower breast cell proliferation in premenopausal women. Effects of UPA on the endometrium continue to be studied and are reassuring. COC use has not been found to lower breast cell proliferation and is not associated with any decrease in risk of breast cancer.
The changes in breast cell proliferation will also be compared to changes seen on breast MRI. If these are highly correlated future studies will be able to be done without the need for breast biopsies.
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.
The goal of this study is to better understand what women are thinking about and feeling as they decide on their cancer treatments. The results of this study may help researchers develop new interventions that may better assist women newly diagnosed with breast cancer with their treatment decisions.
Women diagnosed with breast cancer are choosing bilateral mastectomy (BLM) at increasing rates, currently 14.3%, and 33% of those under 40. This is happening despite evidence that there is no survival benefit from BLM, along with surgical complications and other serious medical and personal costs, compared with more conservative approaches. Women’s anxiety about recurrence is critical to this decision, so their choice may in large part reflect the way they experience and regulate affect. To understand the neurobiological and affective determinants of the choice of BLM, and thereby identify future opportunities for new interventions, we propose to examine the relationship between affect reactivity and regulation and women’s decisions regarding BLM after initial diagnosis of breast cancer. We will also examine the impact of affect management and treatment decisions on subsequent psychosocial functioning. Our Specific Aims are to: 1) Examine affect reactivity and regulation among women with a recent diagnosis of breast cancer in comparison to healthy controls; 2) Relate affect reactivity and regulation to choice of BLM; and 3) Assess long term functional consequences of BLM decision and affect reactivity and regulation. This study will provide an empirical basis for better assisting patients in making difficult but important choices regarding breast cancer treatment alternatives.
The purpose of this study is to see how well two different types of group programs—mindfulness-meditation classes and survivorship education classes—meet the needs of young survivors. Up to 360 women will take part in this study.
This is a multi-site, randomized, three arm, Phase III trial that will evaluate the efficacy of two distinct types of group interventions that are specially designed for younger women who are more than 6 months post initial treatment for breast cancer. The first intervention is a mindfulness meditation-based intervention focused on improving psychological, behavioral, and biological function in younger breast cancer survivors that is adapted from an institutional program in place for the general public at UCLA’s Semel Institute for Neuroscience and Human Behavior. The second intervention is a 6-week didactic group-based survivorship education seminar series that will review specific topics of importance to younger breast cancer survivors including: quality of life after breast cancer; medical management and quality of care post treatment; relationships and work-life balance; body image, sexuality and fertility; energy balance, nutrition, and physical activity; cancer in the family, genetics, and related issues. This curriculum has been adapted from two studies already completed by the investigators, and has a standardized slide set, and will be delivered by a health educator or advanced practice nurse at each of the participating institutions. There will be a maintenance period that follows the 6-week group interventions to help sustain both mindfulness and health behaviors. The third arm of the study (Arm C) will include a usual care group with delayed intervention offered to the participants after they have completed parallel outcome assessments alongside the participants receiving the two interventions (Arm A and Arm B), but not until the end of data collection (6 months after the post-intervention assessments for the cohort).
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.