Hormone, Psychologic & Immunologic Factors & BC Survivorship

Institution: University of California, San Diego
Investigator(s): Hillary  Klonoff-Cohen , Ph.D. -
Award Cycle: 2004 (Cycle 10) Grant #: 10PB-0012 Award: $286,036
Award Type: Request for Applications
Research Priorities
Sociocultural, Behavioral, and Psychological Issues>Sociocultural, Behavioral, and Psychological Issues: the human side



Initial Award Abstract (2004)
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:
  1. 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).
  2. Lifetime stress and timing of surgery may also affect survival.
  3. 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.
  4. NK cell activity (NKCA) will be higher at pre-surgery in subjects who remain healthy compared to those who experience a recurrence.
  5. Optimism, strong social support, coping skills, and quality of life will have an influence on NKCA.
  6. 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.


Final Report (2008)
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).