Timing of Breast Cancer Surgery, Menstrual Cycle & Prognosis

Institution: University of California, San Diego
Investigator(s): Hillary  Klonoff-Cohen , Ph.D. - Hungyi  Shau , Ph.D. - Helena  Chang , M.D., Ph.D. -
Award Cycle: 1998 (Cycle IV) Grant #: 4EB-5900 Award: $506,070
Award Type: TRC Full Research Award
Research Priorities
Innovative Treatments>Gene therapy and other treatments: new frontiers



Initial Award Abstract (1998)
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.


Final Report (2003)
In 2003, there were 211,300 new cases of invasive breast cancer and an estimated 55,700 addition cases of in situ breast cancer. The purpose of this study was to examine whether breast cancer surgery (i.e., lumpectomy, simple mastectomy, modified radical mastectomy) conducted during a particular phase of the menstrual cycle (i.e., early or late luteal or follicular) had an impact on long-term outcomes (i.e., recurrence, remaining healthy or death) among different racial groups. Scheduling breast cancer surgery around the menstrual cycle may have greater efficacy and result in fewer side effects than conventional therapies.

The preliminary analysis presented here is based on a sub-sample (n=200) of White, African American, Hispanic and Asian/Pacific Islander women who underwent surgery for primary carcinoma of the breast between 1998-2003, at UCLA Revlon Breast Cancer Center, Los Angeles County-University of Southern California, and Kenneth Norris Hospital. All women were interviewed by telephone 24 hours before surgery to obtain demographic, reproductive, medical, psychosocial, nutritional, occupational, and environmental information. In addition urine was collected daily, beginning 24 hours before surgery, and extending until the onset of the next menstrual cycle, in order to pinpoint the exact hormonal profile of the menstrual cycle. On average, the women were 40 years of age (range: 28-51 years) at the time of surgery, and were representative of all racial/ethnic groups in Southern California: Caucasian, 50.0%; Hispanic, 27.2%; Asian, 9.1%; Pacific Islander, 2.3%; African American, 2.3%; and Other/Mixed, 9.1%. Approximately 50% of women received their bachelor's degrees, while a further 21% had a total of 17-25 years of education. The mean number of years of education was 14 years (2-25 years) and ninety-one percent of women were employed at the time of diagnosis. Forty-three percent of women reported smoking (>100 cigarettes) during their lifetime, and 41% were exposed to second-hand smoke from their parents, spouses, or other adults. The majority of women (84%) reported consuming alcohol on a social or regular basis (>1 drink/week). The average age at menarche was 12.95 years (range: 10-15 years), and all women reported having regular menses. A total of 68% of women reported using oral contraceptives in their lifetime. Only 48% of the women ever breastfed. The overall distribution for stage of disease at diagnosis consisted of Stage 1 (21%), Stage 2 (45%), Stage 3 (5%), Stage 4 (3%), and unknown (24%). Fifty-three percent of women had ER positive tumors. Treatment options consisted of the following: 57% of women underwent breast conservation therapy, 30% had a mastectomy, 2.3% had surgery, NOS, 2.3% had a combination, and 9.1% were unknown. The overall recurrence rate was 20.5% for the sample. When menstrual phase was divided as day 1-14 for the follicular phase and day 15 to the end of cycle as the luteal phase (based on self-report of the last 3 menstrual cycles), there was no statistically significant difference between the healthy and recurrent groups. However, when the menstrual phase was pinpointed according to the urine hormone measures, there was a statistically significant difference between the two groups of women (OR=2.12, p=0.04). Hence, women who were operated on in the follicular phase had a worse outcome (i.e., recurrence or death) than women in their luteal phase, while adjusting for stage of breast cancer, type of surgery, family history, and age. Estrogen receptor status, family history of breast cancer, and oral contraceptive use did not appear to substantially change the association. If these findings are replicated with the total sample, and subsequently in randomized clinical trials, this translational research (i.e., timing breast cancer surgery around the woman's menstrual cycle), could be fairly easily implemented into the clinical arena as a simple, but powerful therapeutic tool, that could potentially extend and/ or save a substantial number of women's lives.