Initial Award Abstract |
Breast cancer follow-up research has focused solely on documenting distress and dysfunction; however, cancer survivors exhibit similar or better adjustment compared with medical and healthy controls. Approximately 60-90% of breast cancer survivors report beneficial changes, including greater life appreciation and meaning. Positive and negative outcomes are not mutually exclusive, which supports a multidimensional conceptualization of adjustment in which health and dysfunction may exist. The purpose of "Looking forward to LIFE" is to investigate the relationship between the Luteal phase, Immunologic Factors, and Emotional stress, to maximize breast cancer survivorship.
This will be the first study to date to investigate the role that sex hormones (i.e., estrogen, progesterone, FSH, LH) at the time of surgery, procedural and chronic stress (i.e., cortisol), and the immune system (i.e. natural killer cells) play in predicting health/recurrence in breast cancer survivors. The major hypothesis of this new prospective study is to determine whether timing of surgery during the luteal phase, low procedural and lifetime stress, and higher Natural Killer Cell Activity may interact, thereby increasing breast cancer survival. There are five aspects of this hypothesis that we will examine in detail:
- The phase of the menstrual cycle and procedural stress (cortisol) measured
at the time of surgery may predict survivorship (i.e., health, recurrence,
metastases, death).
- Lifetime stress and timing of surgery may also affect survival.
- High quality social support, coping responses, optimistic attitude, and
quality of life will contribute to a healthy outcome vs. breast cancer recurrence
during the study period.
- NK cell activity (NKCA) will be higher at pre-surgery in subjects who
remain healthy compared to those who experience a recurrence.
- Optimism, strong social support, coping skills, and quality of life will
have an influence on NKCA.
- Procedural and lifetime stress, phase of menstrual cycle during surgery,
stress hormones and immunologic factors (NKCA) may all contribute to breast
cancer survivorship.
The study sample will consist of 450 White, African-American, Hispanic, Asian, and Pacific Islander women undergoing surgery for primary carcinoma of the breast, recruited from 5 sites in California and one in New York. Each woman will participate in a telephone interview, complete standardized psychological questionnaires, and provide blood samples (for NKCA analyses), urine (e.g., for sex hormones and cortisol [acute stress]) and saliva (for cortisol [chronic stress]) at study entry, 1 month, 3 months, time of recurrence (if applicable), and at completion of study.
From the previous CBCRP study, we determined that surgery during the follicular phase of the menstrual cycle was detrimental to long-term survival. Chronic emotional stress has also been associated with both impaired immune surveillance functions (NKCA) and stress hormone levels. Stress also alters menstrual phase length. If there is a relationship between hormones, psychological, and immunologic factors and survivorship, the positive impact of longer survival and less recurrence, as well as economic savings would be enormous. The clinical application of this study would be to schedule women's surgery according to the menstrual cycle, counsel them to modify their lifetime and acute (procedural) stress, strengthen their optimism, support system, coping skills, and quality of life, which may enhance their immune system, and ultimately provide them with knowledge that could maximize survivorship. |
Progress Report 1 |
|
Breast cancer follow-up research has focused solely on documenting distress and dysfunction; however, cancer survivors exhibit similar or better adjustment compared with medical and healthy controls. Approximately 60-90% of breast cancer survivors report beneficial changes, including greater life appreciation and meaning. Positive and negative outcomes are not mutually exclusive, which supports a multidimensional conceptualization of adjustment in which health and dysfunction may exist. The purpose of "Looking forward to LIFE" is to investigate the relationship between the Luteal phase, Immunologic Factors; and Emotional stress, to maximize breast cancer survivorship. This will be the first study to date, to investigate the role that sex hormones (i.e,, estrogen, progesterone, FSH, LH) at the time of surgery, procedural and chronic stress (i.e,, cortisol), and the immune system (i.e. natural killer cells) play in predicting health/recurrence in breast cancer suervivors.
The major hypothesis of this new prospective study is to determine whether timing of surgery during the luteal phase, low procedural and lifetime stress, and higher Natural Killer Cell Activity may interact, thereby increasing breast cancer survival. The study sample will consist of 450 White, African-American, Hispanic, Asian, and Pacific Islander women undergoing surgery for primary carcinoma of the breast, recruited from 5 sites in California and one in New York.
Each woman will participate in a telephone interview, complete standardized psychological questionnaires, and provide blood samples (for NKCA analyses), urine (e.g., for sex hormones and cortisol [acute stress]) and saliva (for cortisol [chronic stress]) at study entry, 1 month, 3 months, time of recurrence (if applicable), and at completion of study,
From the previous CBCRP study, we determined that surgery during the follicular phase of the menstrual cycle was detrimental to long-term survival. Chronic emotional stress has also been associated with both impaired immune surveillance functions (NKCA) and stress hormone levels. Stress also alters menstrual phase length. If there is a relationship between hormones, psychological, and immunologic factors and survivorship, the positive impact of longer survival and less recurrence, as well as economic savings would be enormous. The clinical application of this study would be to schedule women's surgery according to the menstrual cycle, counsel them to modify their lifetime and acute (procedural) stress, strengthen their optimism, support system, coping skills, and quality of life, which may enhance their immune system, and ultimately provide them with knowledge that could maximize survivorship.
This project has been delayed for the period of one year and will begin on July 1, 2005. |
Progress Report 2 |
|
Premenopausal breast cancer recurrence represents a more serious diagnosis than early-stage breast disease, and may be associated with greater psychosocial distress. Factors other than age, treatment, race, number of metastatic nodes, and ER status may play a pivotal role in the health and quality of life of cancer survivors, The overall scientific goal of “Looking forward to LIFE” is to investigate the relationship between the Luteal phase of the menstrual cycle during breast cancer surgery, Immunologic Factors, and Emotional stress, in order to maximize breast cancer survivorship and a first recurrence of breast cancer.
This study is unique because it is a 3-year prospective study which will follow 450 pre-menopausal breast cancer patients of different racial backgrounds, while evaluating the timing of the menstrual cycle during the first definitive breast cancer surgery and time of initial recurrence. In conjunction with detailed telephone interviews, the exact phase of the menstrual cycle will be validated using daily urine measurements of sex hormones and immune function (natural killer cell activity) measured at several time points. A stress profile will be generated with salivary cortisol levels and psychological instruments (for coping, optimism, social support and quality of life).
This project had a delayed start date until July 2005. These are the problems and accompanying solutions we encountered during the first year. The original grant proposed utilizing multiple sites including LAC-USC and UCLA in Los Angeles and NYU in New York. As the project began its development phase, it became apparent that it was not feasible to totally rely on these sites because of: a) funding issues and lack of dedicated personnel, b) the volume of eligible patients, and c) the logistics for preparing and analyzing the blood samples in a timely manner. Hence, at that point we began exploring sites closer to San Diego. The two largest prospects, Kaiser Permanente and The Naval Medical Center of San Diego were identified and contacted. Both these facilities have a tremendous volume of patients and superior medical records, but historically have been difficult to engage in cancer research. Negotiations have continued and look very promising. In addition, Berkeley, Cedar Sinai, Arroyo Grande Community Hospital and the Imperial Valley Cancer Center are also part of the network and are currently under consideration. With the additions of these institutions, it is anticipated that the necessary progress will be made towards accomplishing all the specific aims. The significance of the research findings may ultimately result in women proactively participating in: their own treatment choices (timing of surgery), and strategies to diminish procedural and chronic stress and enhance quality of life, which may positively affect their immune system and maximize LIFE. |
Progress Report 3 |
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As breast cancer rates continue to rise across North America, women are continually bombarded with information about suggested causes and possible ways to prevent breast cancer and its recurrence. Many breast cancer survivors believe they can prevent recurrence by psychological means. This will be the first study to investigate the role that hormones (i.e., estrogens, progesterone, FSH, LH) at the time of surgery, stress hormones (cortisol), and Natural Killer (NK) cells play on breast cancer survivorship. Furthermore, this research could contribute to an understanding of differences in breast cancer survival among different ethnic groups
This 3-year prospective study is in the process of recruiting approximately 400 pre-menopausal breast cancer patients of different racial backgrounds (whites, African-Americans, Asians, Pacific Islanders, and Hispanics), from the time of the first definitive breast cancer surgery until time of initial recurrence or continued health. Women are currently participating in detailed telephone interviews, and providing daily urine samples, in order to measure estradiol, progesterone, LH, and FSH levels (and pinpoint the menstrual cycle), and blood samples to measure immune function (i.e., natural killer cell activity [NKCA]) at the time of surgery, 1 month and 3 months post-surgery, at recurrence, and at study end. As well, patients’ salivary and urinary cortisol levels (for chronic and acute stress) and psychological measures (for coping, optimism, social support and quality of life) are being used to determine the women’s longitudinal stress profile. This study did not begin until July 2005 because of Human Subjects requirements. In the next year (2005-2006), we were identifying sites, and had not yet recruited any patients.
Progress made towards accomplishing the specific aims for this year is as follows. Six new recruitment sites have been added to the existing UCSD Moores Cancer Center site, and we are now actively recruiting patients. The final site was signed up in March 2007. In the past 3 months, we have already recruited 20 patients, interviewed them, and collected the necessary samples. Now that we have all clinical sites in place, rigorous recruitment will occur. The prospective labs are analyzing the sex hormones, cortisol, and NK cell activity. As well, we are continuing to conduct interviews, medical record abstractions, sample collection, and data entry. Massive recruitment will continue in order to successfully complete the specific aims. If there is a relationship between sex hormones, psychological and immunologic factors, and breast cancer survivorship these findings could be translated into the clinical arena. Hence, women may proactively participate in: a) their treatment choices (i.e., scheduling timing of surgery around the menstrual cycle) and b) psychological strategies to diminish procedural and chronic stress and enhance quality of life, which may positively affect their immune system and maximize LIFE (i.e., survival). |
Final Report |
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There are currently 178,480 new of cases of invasive breast cancer, 62,030 additional cases of in situ breast cancer, and approximately 40,460 deaths as a result of this disease each year in the US (ACS 2007). Identifying new ways to treat premenopausal breast cancer patients is vital. This will be the first study to investigate the role that hormones (i.e., estrogens, progesterone, FSH, LH) at the time of surgery, stress hormones (cortisol), and Natural Killer (NK) cells play on breast cancer survivorship. The aim of this 3-year pilot study was to recruit pre-menopausal breast cancer patients of different racial backgrounds (whites, African-Americans, Asians, Pacific Islanders, and Hispanics), from the time of the first definitive breast cancer surgery until time of initial recurrence or continued health. Women participated in detailed telephone interviews, and provided daily urine samples, in order to measure estradiol, progesterone, LH, and FSH levels (and pinpoint the menstrual cycle) and blood samples to measure immune function (i.e., natural killer cell activity [NKCA]) at multiple time points. As well, patients’ salivary and urinary cortisol levels (for chronic and acute stress) and psychological measures were used to determine the women’s longitudinal stress profile.
This study did not begin until July 2005 because of Human Subjects requirements. In the next year (2005-2006), we identified sites, and in 2006-2007, we began patient recruitment. This year, we vigorously approached multiple sites and enlisted the support of several prestigious institutions, including Cedars Sinai, Harbor UCLA, UC Irvine, City of Hope, and Sharp Hospital. This supplemented our existing sites at UCSD, University of Rochester, New York University, and Naval Medical Center of San Diego. We diligently completed IRB approval for all of these sites. As of February 2008, we recruited 85 patients, interviewed them, and collected the necessary samples. We had conservatively saved almost all the funds to successfully accomplish our goals. However, CBCRP decided to end this project due to limited progress, and left us with only a small amount of monies to complete a pilot study, rather than the proposed large study. Thus, at present, it is unknown whether the effect of the menstrual cycle in combination with psychological and immunological factors will truly extend survival. We are therefore submitting this proposal to other funding agencies in order to conduct the fully proposed study. If there is a relationship between sex hormones, psychological and immunological factors, and breast cancer survivorship these findings could be rapidly translated into the clinical arena. Hence, women could proactively participate in: a) their treatment choices (i.e., scheduling timing of surgery around the menstrual cycle) and b) psychological strategies to diminish procedural and chronic stress and enhance quality of life, which may positively affect their immune system and maximize LIFE (i.e., survival). |
Initial Award Abstract |
Breast cancer follow-up research has focused solely on documenting distress and dysfunction; however, cancer survivors exhibit similar or better adjustment compared with medical and healthy controls. Approximately 60-90% of breast cancer survivors report beneficial changes, including greater life appreciation and meaning. Positive and negative outcomes are not mutually exclusive, which supports a multidimensional conceptualization of adjustment in which health and dysfunction may exist. The purpose of "Looking forward to LIFE" is to investigate the relationship between the Luteal phase, Immunologic Factors, and Emotional stress, to maximize breast cancer survivorship.
This will be the first study to date to investigate the role that sex hormones (i.e., estrogen, progesterone, FSH, LH) at the time of surgery, procedural and chronic stress (i.e., cortisol), and the immune system (i.e. natural killer cells) play in predicting health/recurrence in breast cancer survivors. The major hypothesis of this new prospective study is to determine whether timing of surgery during the luteal phase, low procedural and lifetime stress, and higher Natural Killer Cell Activity may interact, thereby increasing breast cancer survival. There are five aspects of this hypothesis that we will examine in detail:- The phase of the menstrual cycle and procedural stress (cortisol) measured
at the time of surgery may predict survivorship (i.e., health, recurrence,
metastases, death).
- Lifetime stress and timing of surgery may also affect survival.
- High quality social support, coping responses, optimistic attitude, and
quality of life will contribute to a healthy outcome vs. breast cancer recurrence
during the study period.
- NK cell activity (NKCA) will be higher at pre-surgery in subjects who
remain healthy compared to those who experience a recurrence.
- Optimism, strong social support, coping skills, and quality of life will
have an influence on NKCA.
- Procedural and lifetime stress, phase of menstrual cycle during surgery,
stress hormones and immunologic factors (NKCA) may all contribute to breast
cancer survivorship.
The study sample will consist of 450 White, African-American, Hispanic, Asian, and Pacific Islander women undergoing surgery for primary carcinoma of the breast, recruited from 5 sites in California and one in New York. Each woman will participate in a telephone interview, complete standardized psychological questionnaires, and provide blood samples (for NKCA analyses), urine (e.g., for sex hormones and cortisol [acute stress]) and saliva (for cortisol [chronic stress]) at study entry, 1 month, 3 months, time of recurrence (if applicable), and at completion of study.
From the previous CBCRP study, we determined that surgery during the follicular phase of the menstrual cycle was detrimental to long-term survival. Chronic emotional stress has also been associated with both impaired immune surveillance functions (NKCA) and stress hormone levels. Stress also alters menstrual phase length. If there is a relationship between hormones, psychological, and immunologic factors and survivorship, the positive impact of longer survival and less recurrence, as well as economic savings would be enormous. The clinical application of this study would be to schedule women's surgery according to the menstrual cycle, counsel them to modify their lifetime and acute (procedural) stress, strengthen their optimism, support system, coping skills, and quality of life, which may enhance their immune system, and ultimately provide them with knowledge that could maximize survivorship. |
