# MANIPULATION OF BREAST CANCER CELL KINETICS BY ESTROGEN

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 1988 · $108,480

## Abstract

Investigators have long been interested in improving response rates in
metastic breast cancer by attempting to increase proliferative activity
(PA) and then applying cell cycle specific chemotherapy at the presumed
height of stimulation.  In vitro studies have shown that an increase in PA
results from exposure to .5-1 nM 17-B estradiol(E2) alhough greater than 10
nM may be inhibitory.  Clinical trials in which patients have been
pretreated with oral estrogens before receiving chemotherapy have had mixed
results.  However all these trials have (1) used antiestrogens immediately
preceeding the estrogen which may have prevented stimulation, (2) have not
measured serum levels of E2 or antiestrogens and (3) have not obtained
serial tumor samples to document if or when treatment was actually
producing an increase in the number of cells in cycle.

In a preliminary study utilizing once daily oral estradiol and serial
biopsies, we found an increase in S phase in 2/4 patients.  However, time
to increase in S phase was variable and continuous 1 nM E2 levels were not
maintained.  We did find that micronized E2 vaginal suppositories reliably
produced .5-1 nM E2 levels without large biologically important increases
in estrone (E1).  Peak E2 levels were present within 1 hour of suppository
insertion and E2 and FSH levels approached baseline within 48 hours of
discontinuation following chronic (72-96 hour) adminisration.  Further
studies are needed to address the following quastions.  1) What proportion
of patients will exhibit a significant increase in cells in cycle if
exposed to continuouus 1 bN levels of E2 which closely mimic tissue culture
conditions?  2) When can an increase in PA be expected to occur relative to
initiation of E2.  We will address these questions by obtaining serial
samples of tumor from patients with locally advanced disease as well as
from patients with soft tissue metastases and malignant pleural effusions
before and during the initial 72 hours of intravaginal E2 administration.
During and after the intravaginal E2 we will also monitor E2, estrone (E1)
and FSH levels.

At the conclusion of this study we will know if and when E2 can induce an
increase in PA in a significant number of patients.  This information will
then be used to design a randomized trial questionning the raltive merit of
hormone synchronization for the treatment of breast cancer.

## Key facts

- **NIH application ID:** 3177620
- **Project number:** 5R01CA039004-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **SAM.gov UEI:** YXJGGNC5J269
- **Principal Investigator:** CAROL J. FABIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $108,480
- **Award type:** 5
- **Project period:** 1986-04-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177620

## Citation

> US National Institutes of Health, RePORTER application 3177620, MANIPULATION OF BREAST CANCER CELL KINETICS BY ESTROGEN (5R01CA039004-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177620. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*