Timing of Breast Cancer Surgery, Menstrual Cycle & Prognosis

 

2002

 

Hillary S. Klonoff-Cohen, Ph.D.

University of California, San Diego- Department of Family and Preventive Medicine

Helena Chang, M.D., Ph.D.
University of California, Los Angeles- Revlon/UCLA Breast Center

Hungyi Shau, Ph.D.
University of California, Los Angeles- Division of Oncology

Award Type: TRC- Full Research
Duration: 3 yrs., 1998-2001



Initial Award Abstract

Surgery is the most common treatment for early breast cancer. There may be a particular time during the menstrual cycle when breast cancer surgery is less successful and results in decreased survival. A multi-disciplinary research team consisting of an epidemiologist, reproductive hormone specialist, basic immunologist, and three breast cancer surgeons will evaluate breast cancer patients’ hormonal status to determine whether breast cancer surgery during a particular time of the menstrual cycle known as the follicular phase (i.e., occurring between menstruation and ovulation) will increase the chance that the tumor will re-occur. This three-year study will follow 400 White, African-American, Hispanic, and Asian or Pacific Islander premenopausal women who will undergo surgery for breast cancer at four different hospitals (University of California San Diego, University of California Los Angeles, Los Angeles County-University of Southern California, and USC/Kenneth Norris) between July 1998 and June 2001. Patients with other cancers, or those with a hysterectomy, will not be included in the study. A pathologist will classify the type of breast cancer and where it has spread. The medical and reproductive histories, as well as other important information will be obtained from a detailed telephone interview, medical records, and laboratory results. The phase of the menstrual cycle (i.e., early or late follicular or luteal) will be determined by measuring specific hormones in the urine (e.g., progesterone, estradiol, follicle stimulating hormone, and leutinizing hormone) on a daily basis, starting on the day of surgery, and continuing until the onset of the next menstrual cycle. Most factors that influence the long-term outcome of breast cancer are beyond the doctor’s control. This study will work with the body’s predictable biologic rhythms (referred to as chronotherapy), in order to search for a better way to treat breast cancer. If the timing of surgical treatment during a particular phase of the menstrual cycle plays a significant role in survival from premenopausal breast cancer, this could possibly extend and/or save a great number of women’s lives. In fact, the greatest benefit for timing of surgery would be to those young women at highest risk of breast cancer recurrence. The ease of modifying the timing of breast cancer surgery in the clinical setting could be very rapid and inexpensive; hence, timing of surgery could serve as a potentially simple, but powerful therapeutic tool.

 

Progress Report, Year 1 (1999)

The timing of surgery during a specific phase of the menstrual cycle is complicated and controversial. Evidence suggests that there may be decreased survival among women with positive, axillary lymph node involvement surgically treated during the follicular phase of the cycle. A cross-disciplinary research team uniting an epidemiologist, reproductive endocrinologist, immunologist, three surgical oncologists, and a biostatistician are examining the following hypothesis: to determine whether breast cancer surgical procedures performed during the follicular phase of the menstrual cycle have a positive or negative impact on recurrence or death among different racial groups. This prospective study will recruit 400 White, African-American, Hispanic, and Asian or Pacific Islander premenopausal women undergoing diagnosis and surgery for primary carcinoma of the breast between 1999 and 2001, at four sites (University of California, San Diego, Los Angeles County-University of Southern California, Kenneth Norris, and UCLA Revlon Breast Cancer Center hospitals). Pertinent information, including demographic, reproductive, medical, psychosocial, diet, occupational and environmental factors will be derived from detailed telephone interviews, and validated with medical records and laboratory results. Menstrual cycle phase will be classified as follicular (early or late), luteal (early or late) and midcycle. In addition, the exact hormonal profile of the menstrual cycle will be objectively measured with daily urine measurements, starting before surgery (baseline) and extending until the onset of the next menstrual cycle. Blood samples will also be collected 24 hours before and after surgery, and again at approximately seven days, and three months, post-surgery, and archived for future analyses.

The initial three months of this project have been devoted to setting up the project, including developing and pilot-testing the interview and data abstraction forms, coordinating the surgeons and centers, training the staff research associate and clinical nurses, and establishing a standardized laboratory collection, transport, and analysis protocol. Consecutive enrollment of eligible breast cancer patients, interviews, medical record abstractions, laboratory analysis, and data entry, will begin in May 1999, and continue for an additional 21 months.

Most factors that influence the prognosis of breast cancer are beyond the clinician’s control. If the timing of surgical treatment plays a role in the ultimate prognosis for premenopausal breast cancer patients, this translational research could be easily implemented, and have an immediate impact, by potentially extending and/or saving a substantial number of women’s lives.

 

Progress Report, Year 2 (2000)

There may be decreased survival among women with positive axillary lymph node involvement who undergo surgery during the follicular phase of their menstrual cycle. A multi-disciplinary research team is addressing whether breast cancer surgeries conducted during particular phases of the menstrual cycle have an impact on recurrence or death among different racial groups. This prospective study is currently in the process of recruiting 400 White, African-American, Hispanic and Asian/Pacific Islander premenopausal women undergoing diagnosis and surgery for primary carcinoma of the breast, at UCLA Revlon Breast Cancer Center, Los-Angeles County-University of Southern California and Kenneth Norris Hospital. Patients with concomitant distant metastases, previous malignant disease, or bilateral breast cancer, are excluded. The eligible women are participating in a detailed telephone interview to provide demographic, reproductive, medical, psychosocial, nutritional, occupational, and environmental information. The exact hormonal profile of their menstrual cycle is being objectively measured with daily urine measurements, starting 24 hours before and after surgery, and extending until the onset of the next menstrual cycle; menstrual cycle is classified as early or late follicular or luteal phases. Blood samples are being collected at 24 hours before and after surgery, and at 3 months and 1 year post-surgery. There is also a systematic collection and banking of additional blood specimens that will be used to test other compelling hypotheses or biological rationales concerning the putative relationship.

This past year has been devoted to recruiting eligible breast cancer patients, conducting interviews, collecting samples and data entry. To maximize patient recruitment, a minimum of one additional site has been targeted: New York University, which has a large ethnically diverse population of premenopausal breast cancer patients. The available data has been cleaned and entered; there are currently no experimental results available. This study will work with the body’s predictable biologic rhythms (e.g., chronotherapy) to find a potentially simple, but powerful therapeutic tool to treat breast cancer. If the timing of surgery plays a role in the ultimate prognosis of premenopausal breast cancer patients, this translational research could be easily implemented and extend (or save) a substantial number of women’s lives.

Progress Report, Year 3 (2001)

A multi disciplinary research team (i.e., epidemiologist, surgical oncologists, reproductive endocrinologists, and immunologist) is examining whether breast cancer surgeries conducted during particular phases of the menstrual cycle (i.e., early or late luteal or follicular) have an impact on recurrence, survival, or death among different racial groups. This past year has been entirely devoted to identifying and recruiting White, African American, Hispanic, and Asian/Pacific Islander pre menopausal women undergoing diagnosis and surgery for primary carcinoma of the breast, at UCLA Revlon Breast Cancer Center, Los Angeles County University of Southern California, and Kenneth Norris Hospital. Very strict exclusion criteria (i.e., women with concomitant distant metastases, previous malignant disease, or bilateral breast cancer, currently pregnant or breastfeeding) have hampered the recruitment process.

The eligible women are interviewed by telephone 24 hours before surgery to obtain demographic, reproductive, medical, psychosocial, nutritional, occupational, and environmental information. In order to pinpoint the exact hormonal profile of the menstrual cycle, urine is collected daily, beginning 24 hours before surgery, and extending until the onset of the next menstrual cycle. In addition, blood samples are being collected 24 hours before and after surgery, and at 3 months and 1 year, thereafter. There is also systematic collection and banking of additional blood specimens for future testing of other compelling hypotheses. To maximize patient recruitment, additional sites have been targeted which have large ethnically diverse populations of pre menopausal breast cancer patients. With continued involvement of these sites and new sites at Scripps Cancer Center in San Diego and Long Beach/UCLA, assistance from newly hired personnel in Los Angeles County, and the addition of a no cost extension year, this project should successfully be completed. At the conclusion, if a particular phase of the menstrual cycle influences the ultimate prognosis of pre menopausal breast cancer patients, this translational research could be fairly easily implemented into the clinical arena (specifically timing breast cancer surgery around the woman’s menstrual cycle), potentially extending and/or saving a substantial number of women’s lives.

 

PG

Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.
About Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.