CELL PROLIFERATION OF EPITHELIAL CELLS IN NORMAL HUMAN BREAST TISSUE DURING ARTIFICIAL MENSTRUAL CYCLES REGULATED BY ORAL CONTRACEPTIVES BY THE EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN

Authors

  • Débora Garcia Y. Narvaiza Disciplina de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp - EPM).
  • Afonso Celso Pinto Nazário Disciplina de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp - EPM).
  • Vânia Nosé Alberti Disciplina de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp - EPM).
  • Edmund Chada Baracat Disciplina de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp - EPM).
  • Geraldo Rodrigues de Lima Disciplina de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp - EPM).

Keywords:

Normal human breast, Oral contraceptives, Proliferating Cell Nuclear Antigen (PCNA)

Abstract

The oral contraceptive effect on normal breast still remains unclear. The few reports
related to cell kinetics on the normal breast epithelium during the use of oral contraceptives
(OCs) are in disagreement and were made without discriminating the sort of OCs.
For those reasons and by the fact that they have been widely used, we propose to
determine the proliferative activity evaluated by the PCNA expression in epithelial cells
of normal breast tissue after the administration of levonorgestrel 0.15 mg and ethinyl
stradiol 0.03 mg during to cycles of 21 days (with seven days between pill packs).
Normal breast tissue was collected at the time of benign lump biopsy by removing
fragments of breast parenchima located at least 1 cm from the lesion. The biopsy took
place between the 22"d and 25,h day of menstrual cycle, and was determined on the basis
of the date of the menstruation and of serum progesterone measurement at the moment
of biopsy.
The material was fixed in 10% formalin for less than 12 hours and processed by
immonohistochemistry (PC-10). In the study group the average PCNA expression was
16.78% where as in the control group was 13.72% (Mann Whitney test p = 0.4173).
Our results showed that there is no difference in PCNA expression among OCs
users during two cycles of treatment.

Downloads

Download data is not yet available.

References

1.ANDERSON TJ, BATTERSBY S, KING RJB,

MCPHERSON K, GOING JJ. Oral contraceptive

use influences resting breast proliferation. Human

Pathol 1989; 20: 1139-44.

2.BATTERSBY S, ANDERSON TJ. Correlation of

proliferative activity in breast tissue using PCNA/

cyclin. Human Pathol 1990; 21: 781 [Letter],

3.BATTERSBY S, ROBERTSON BJ. ANDERSON

TJ, KING RJR, MCPHERSON K. Influence of

menstrual cycle, parity and oral contraceptive use

on steroid hormone receptors in normal breast. Br

J Câncer 1991; 65: 601-7.

4.COHEN BL, KATZ M. Pituitary and ovarian

function in women receiving hormonal contraception. Contraception 1979; 20: 475-87.

5.COLLABORATIVE GROUP ON HORMONAL

FACTORS IN BREAST CÂNCER. Breast câncer

and hormonal contraceptives: collaborative

reanalysis of individual data on 53.297 women with

breast câncer and 100.239 women without breast

câncer from 54 epidemiological studies. Lancet

1996; 347: 1713-27.

6.DICZFALUSY E. Gregory Pincus and steroidal

contraception revisited. Acta Obstet Gynecol Scand

(Suppl) 1982; 105: 7-15.

7.DRIFE JO. The benefits and risks of oral

contraceptives today. 2nd ed. London: The

Parthenon Publishing Group. 1996.

8.EL-RAGHY I. BACK DJ. MAKERAM M et al.

Pharmacokinetics of oral contraceptives steroids

in egyptian women: studies with ovral, nordette

and norminest. Contraception 1986; 33: 379-85.

9.FERGUSON DJP, ANDERSON TJ. Morphological

evaluation of cell turnover in relation to the

menstrual cycle in

"resting" human breast. Br J

Câncer 1981; 44: 177-81.

10.GELB AB. KAMEL OW, LEBRUN DP. WARNKE

RA. Estimation of tumor growth fractions in

archival formalin-fixed, paraffin embedded tissues

using two anti-PCNA/ cyclin monoclonal antibodies. Am J Pathol 1992; 114: 1453-8.

11.GOING JJ, ANDERSON TJ, BATTERSBY S, MACINTYRE CCA. Proliferative and secretory

activity in human breast during natural and artificial

menstrual cycles. Am J Pathol 1988; 30: 193-204.

12.KUHNZ W, AL-YACOUB G, FUHRMEISTER A.

Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral

contraceptive over a treatment period of 3 months

and, after a wash-out phase, a single oral administration of the same contraceptive formulation.

Contraception 1992; 46: 55-69.

13.LOBO RA, STANCZYK FZ. New knowledge in

the physiology of hormonal contraceptives. Am J

Obstet Gynecol 1994; 170: 1499-507.

14.MEYER JS. Cell proliferation in normal human

breast ducts, fibroadenomas, and other ductal

hyperplasias measured by nuclear labeling with

tritiated thymidine. Human Pathol 1977; 8: 67-81.

15.MISHELL JR DR, KLETZKY O A. BRENNER PF.

ROY S, NICOLOFF J. The effect of contraceptive

steroids on hypothalamic-pituitary function. Am J

Obstet Gynecol 1977; 128: 60-74.

16.NAZÁRIO ACP, LIMA GR, SIMÕES MJ, NOVO

NF. Cell kinetics of the human mammary lobule

during the proliferative and secretory phase of the

menstrual cycle. Buli Assoc Anat 1995; 79: 23-7.

17.OLSSON H, JERNSTRÕM H, ALM P et al.

Proliferation of the breast epithelium in relation to

menstrual cycle phase, hormonal use, and

reproductive factors. Breast Câncer Res Treat

1996; 40: 187-96.

18.LIMA GR, BARACAT EC. Ginecologia endócrina.

São Paulo: Atheneu. 1995.

19.TARRICONE JR V. Expressão do antígeno de

proliferação celular (PCNA) no epitélio mamário

normal nas fases foliculare lútea. São Paulo: 1997.

Tese de Mestrado, Escola Paulista de Medicina -

Unifesp.

20.WILLIAMS G, ANDERSON E, HOWELL A et al.

Oral contraceptive (OCP) use increases proliferation

and decreases oestrogen receptor content of

epithelial cells in the normal human breast. Int J

Câncer 1991; 48: 206-10.

Published

2026-07-28

How to Cite

Narvaiza, D. G. Y., Nazário, A. C. P., Alberti, V. N., Baracat, E. C., & de Lima, G. R. (2026). CELL PROLIFERATION OF EPITHELIAL CELLS IN NORMAL HUMAN BREAST TISSUE DURING ARTIFICIAL MENSTRUAL CYCLES REGULATED BY ORAL CONTRACEPTIVES BY THE EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN. Mastology, 10(3). Retrieved from https://mastology.org/journal/article/view/2069

Issue

Section

Original Articles