Saravanan. P.S - NJBMSnjbms.in/uploads/19/3302_pdf.pdf · 2019-02-02 · Original Article Saravanan. P.S.L1, Anu .S2 ABSTRACT Introduction: Prolactin has been proved to be involved

Original Article

1 2Saravanan. P.S.L , Anu .S

ABSTRACT

Introduction: Prolactin has been proved to be involved in mammary cancer development in

humans, but its role in fibroadenoma breast has long been controversial with conflicting reports.

Hence this study was done to find out Prolactin level in women with fibroadenoma and if its role in

development of tumor is proved, then a feasible drug treatment which could reduce the anxiety and

cosmetic problems associated with surgical interventions can be identified.

Objectives:

1. To estimate serum prolactin level in patients with fibroadenoma breast.

2. To compare serum prolactin level of fibroadenoma patients with that of the controls

3. To consider whether prolactin level can be used as an indicator for fibroadenoma breast and has

any relation to the disease progression

Materials and methods: A total of 20 female patients between the age group of 18-40 years

attending Government Medical College Hospital, Madurai have been studied. Among them 13

patients had fibroadenoma of the breast and 7 normal women served as control. Prolactin level was

measured by Immunoradiometric assay.

Results: No significant elevation of prolactin level is seen in women with fibroadenoma breast

(mean=25.75ng/ml) when compared with the control and there is no significant association between

increased prolactin level and breast fibroadenoma (X2 = 1.83; p = 0.1759).

Conclusion: Prolactin level is not significantly increased in fibroadenoma breast patients. A large

scale study is required for a stronger confirmation. Studying the role of locally produced prolactin

and mutation in prolactin receptors might help in proper therapeutic management.

Key Words: Fibroadenoma, Benign tumor, Females, Prolactin.

INTRODUCTION:

n recent times the incidence of tumors of

breast is quite alarming all over the world .The Imost common benign tumor of the breast is 1,2fibroadenoma and its overall incidence is 2.2%.

It is common in young women. It originates from

the breast lobule and shows evidence of both

connective tissue and epithelial proliferation. The

Address for correspondence:

S.Anu, Professor and Head, Department of Physiology, Vellammal Medical College and Hospital, Madurai.

Mobile : 98943 97527 Email id: [email protected]

1Professor, Institute of Physiology, Madurai Medical College, Madurai.2Professor & Head, Department of Physiology, Velammal Medical College and Hospital, Madurai.

National Journal of Basic Medical Sciences | Volume 7 | Issue 4 | 2017

Prolactin Level In Women With Fibroadenoma

Breast-A Cross Sectional Study

exact etiology of a fibroadenoma is still unknown,

while hypersensitivity to estrogen within a lobule

has been suggested.

Fibroadenomas are characteristically mobile

tumors, varying in size between 1 cm and 10 cm and

frequently occur in the upper outer quadrant of the

breasts. Women with fibroadenomas have 2.17 3times risk for breast cancer.

240

241National Journal of Basic Medical Sciences | Volume 7 | Issue 4 | 2017

Development of breast involves coordinated action

of many hormones including prolactin, estrogen,

progesterone, gluocorticoids, insulin, growth

hormone and thyroid hormone. Duct growth is

promoted by estrogen, alveolar development is

controlled by prolactin & progesterone and 4

lactation is mediated by prolactin. The fact that

Prolactin (PRL) is important in all phases of breast

development and critical to breast control has been 5established by careful studies. Prolactin stimulates

mammary epithelial cell proliferation in the

presence of estrogen and quickens lobuloalveolar

development in the presence of progesterone.

The circulating prolactin levels are lowest at

midday and peak levels occur during middle to end 6

of night. Prolactin level is found to increase during 7menarche as well as in the premenopausal women.

Higher levels are also found during pregnancy both

in the mother and the fetus. At term prolactin level

is 10 times as in a non pregnant women. High levels

of prolactin appear to be essential for the initiation

of lactation. Once breast enzyme systems are

activated, lactation can continue with even low

levels of prolactin. Reduction in the prolactin level 8following menopause has been reported.

Role of prolactin in galactorrhea and infertility in

women is largely known. Locally produced

Prolactin acts as an autocrine / paracine factor in 9

breast tumor evolution. JAK2 is required for PRL

mediated maintenance of differentiated alveolar

cells. PRL may promote breast cancer via JAK 102/STAT 2 signaling pathway. Though little is

produced in the mammary gland, due to local

availability it plays an important role in tumor

formation.

Breast tumor cells also express higher levels of

PRL receptor when compared to healthy tissue.

Estrogen stimulates PRL secretion and also up

regulates human PRL receptor gene expression in

the progress of the disease. Conflicting reports are

found regarding the involvement of Prolactin in

cases of tumors of breast. Hence this study is taken

up to find whether the increasing incidence of

fibroadenoma breast has any relation to the

Prolactin level of the individual and also its

relevance to the tumor.

MATERIALS & METHODS:

The Study was done at Government Rajaji Medical

College Hospital, Madurai after getting clearance

from the Institutional Ethical Committee.

Twenty subjects in the age group of 18-40yrs were

chosen for the study by simple random sampling.

13 of them had benign tumor (fibroadenoma) of the

breast. Patients were identified following

histopathological examination of the tissue

removed at surgery. All of them were in the

premenopausal group. Seven premenopausal

normal women having similar age and weight

were selected and served as control.

After getting consent from the selected individuals,

the Proforma was filled in eliciting the required

data to find the possible risk factors. All patients

included in this study were without any prior

treatment. Women who were pregnant and / or

lactating were excluded from the study. In all

subjects blood samples were taken during the

follicular phase of the menstrual cycle.

As far as could be ascertained, no patient was

receiving phenothiazines, L-Dopa, monoamine

Dr. S. Anu, et.al : Prolactin level in women with Fibroadenoma breast


oxidase inhibitors, or other drugs know to affect the

secretion of prolactin. Each patient had a blood

sample taken between 11.00 am and 5.00 pm and

blood was allowed to clot and the resulting serum

was frozen at -20°C until assayed. Prolactin is

estimated by Immuno Radio Metric Assay

(IRMA).

Principle of the test:

This immunoradiometric assay is a non

competitive assay technique to quantitate prolactin

in serum sample. In IRMA, two antibodies

generated against different portions (epitopes) of

the same antigen are used. The capture antibody is

coupled to magnetic particles and used as the solid

phase and the detection antibody is radiolabelled 125

with I. When antigens (standards or sample) are

incubated with the tracer and the solid phase, it

simultaneously binds to both the antibodies in a

bridge or sandwich fashion. Their entire complex

remains bound to the magnetic particle. The bound

radioactivity associated is then quantitated using a 1 2 5 gamma counter calibrated for I. The

concentration of prolactin in the sample is directly

proportional to the radio activity. The concentration

of prolactin of unknown sample is read off by the

interpolation from the curve.

Statistical analysis:

The quantitative data was checked for normality

and summarized using mean/median and standard

deviation / interquartile range as appropriate.

Categorical data is summarized as frequencies and

percentages. Prolactin level in fibroadenoma group

and control group was compared using student t test

& chi square test. P value ˂ 0.05 is the cut off to

determine statistical significance.

RESULTS:

Table-1. Mean Prolactin level in Fibroadenoma

patients.

Table-2. Association of Prolactin level with

fibroadenoma breast:

Chi-square test:

X2 = 1.83 p = 0.1759

Table-3. Student t Test:

OBSERVATION:

Among 07 controls ,all were with normal Prolactin

level ˂ 20mg/ml.

Among 13 fibroadenoma breast cases,

5 i.e. 38.5% - were with increased prolactin level

8 i.e. 61.5% - were with normal prolactin level

DISCUSSION:

Evidence that Prolactin is a carcinogen in rat 11mammary cancer was presented in 1969. Since

then there are numerous reports in the literature of

investigation of relationship between Prolactin and

various aspects of breast tumors and many have

found suggestive association between Prolactin

and breast cancer. Studies for Prolactin level in



fibroadenoma breast patients have also produced

conflicting reports. Though few studies report that

prolactin level is elevated in fibroadenoma breast

patients, there are studies which had showed

normal prolactin level in patients with benign 12

breast tumors. In another study, only 27% & 5% 13,14

of fibroadenoma patients had elevated prolactin.

The present study results also showed increased

prolactin levels only in 38.5% of fibroadenoma

patients with normal prolactin level in the

remaining 61.5% (as shown in table1).There is no

significant increase in the level of prolactin in

fibroadenoma patients when compared with the

control (Table 2,3).

The interpretation of the result obtained in present

study depends on the confidence with which a

single prolactin estimate between 9.30 a.m to 5.00

p.m represents the prolactin status of the patient.

The defined time period was chosen to avoid major

variation due to the diurnal rhythm of prolactin. By

9.30 a.m the fall of prolactin levels from their

nocturnal sleep induced peak has reached a 15

plateau

Though stress increases the prolactin level, a

number of investigations have concluded that 16

venepuncture rarely induces prolactin release.

Studies have shown that prolactin levels vary 17depending upon the phase of menstrual cycle. In

the present study since blood samples are taken

only in the follicular phase of the premenopausal

subjects, the difference found in prolactin level

cannot be attributed to the phase of menstrual cycle.

Similarly because the blood sample is taken prior to

any treatment, the difference in the level cannot be

attributed to surgery induced increased prolactin

level or chemotherapy or Hormonal therapy

induced suppression of prolactin level. Also studies

show that routine breast examination does not alter 18serum prolactin level. Though artefactual high

Prolactin levels may occur due to pulsatile release,

number of investigations have concluded that

frequent sampling does not improve the value of a 19

result. These studies suggest that the result of the

single estimate of prolactin level in the present

study may be viewed with confidence.

Within the last few years however, with the advent

in molecular biology several studies have

supported the role of prolactin in fibroadenoma.

Prolactin secretion, in the tumor initation phase

influences the metabolism of mammary epithelium

by increasing its sensitivity to carcinogens and later

directly acting as a promoter of transformed 20

epithelium.

Prolactin alters progesterone and estrogen ratios

and increases the expression of estrogen receptors 21

in mammary gland Estrogen replacement therapy

increased the risk of fibroadenoma by potentiating

the proliferation of mammary epithelial tissue by 22prolactin .Also increased estrogen increases

plasma prolactin levels, which in turn interact with

estradiol to cause mammary gland hypertrophy.

Recent studies have reported that prolactin is also

synthesized and secreted by mammary epithelial

cells. There is an autocrine / paracrine loop of

action of prolactin to promote breast tumor. Hence

another possible mechanism that can lead to tumor

breast might include local over expression of

prolactin inducing morphological and functional

defects in mammary gland in the presence of 23normal serum prolactin. That might be the reason



Dopamine agonists fail to show clinical

improvement in patients with progressing tumor.

Also studies have shown that prolactin receptor

antagonists inhibit the growth of breast cancer cell

lines confirming the fact that prolactin receptors

are up regulated in tumor breast cell lines and also

functional mutation occurs in prolactin 24, 25, 26

receptors.

Prolactin also promotes tumor growth by

modulating cell cycle regulators in mammary 27tumor cells and by stimulating angiogenesis.

Another interesting observation made in mouse

mammary glands is that prolactin promotes tumor 28

growth by its anti apoptotic action via STAT 5. At,

genetic level it was shown that prolactin gene

disruption arrests mammary gland development 29

and retards tumor growth.

The role of prolactin in fibroadenoma is still

controversial. A better understanding of genetic

and molecular characteristics of prolactin is needed

to aid treatment.

CONCLUSION:

In this study, there is no significant elevation of

serum prolactin levels in fibroadenoma breast

when compared to normal. As the number of cases

are few to give an effective interpretation, a

thorough investigation in future is required with

more number of patients. This could open potential

theurapeutic approaches for fibroadenoma. A still

thorough understanding of the role of prolactin and

its receptor in tumorigenesis is needed. Parameters

like the duration of hormone exposure, involved

target tissue and genetic background should also be

studied for understanding the tumorigenic effects

of prolactin.

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Received on 12/06/2017 Revised on 28/06/2017 Accepted on 29/06/2017

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Saravanan. P.S - NJBMSnjbms.in/uploads/19/3302_pdf.pdf · 2019-02-02 · Original Article Saravanan. P.S.L1, Anu .S2 ABSTRACT Introduction: Prolactin has been proved to be involved