Endocrine aspects benign and malignant disorders of the breast
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Endocrine aspects benign and malignant disorders of the breast. Jacek Pytel. Epidemiology. 50%-70% women „have problems with breasts” during their life. Epidemiology. 50% of American women are consulted for breast diseases 25% are undergoed breast biopsy

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Epidemiology
Epidemiology breast

50%-70% women „have problems

with breasts” during their life


Epidemiology1
Epidemiology breast

  • 50% of American women are consulted for breast diseases

  • 25% are undergoed breast biopsy

  • 12% are developed some variant of breast cancer


Epidemiology2
Epidemiology breast

  • Breastcancer –the most commonsite-specificcancerinwomen

  • 33% of allfemalecancers

  • 20% of thecancerrelateddeathsinwommenisresposible of breastcancer


Epidemiology3
Epidemiology breast

  • 211300 invasive breast cancers were diagnosed in the USA in 2003

  • 39800 (18,9%) died from the cancer


Epidemiology4
Epidemiology breast

  • USA

  • 2009 – 192 570 new cases

    40320 (20,9%) died


Epidemiology5
Epidemiology breast

  • 13314new breast cancer were diagnosed in 2006 in Poland; 5221(39,2%) died from the breast cancer

  • 2005 – 13385; 5112 (38,2%)

  • 2000- 10987; (42,9%)


Epidemiology6
Epidemiology breast

  • 2005 – 13385 new cases

    (44,5/100 000)

    5112 died

    2000 – 10987 new cases

    4712 died


Embryology and functional anatomy
Embryology and functional anatomy breast

  • In most mammals, paired breasts develop along two ventral bands of thickened ectoderm (mammary ridges, milk lines) at the fifth or sixth week of fetal development

  • This ridges disappear after short time exept for small portions that may persist in the pectoral region


Embryology and functional anatomy of the breast
Embryology and functional anatomy of the breast breast

Accessory breasts (polymastia)

Accessory nipples (polythelia)

may occur along the milk way





Embryology and functional anatomy of the breast4
Embryology and functional anatomy of the breast breast

  • The breasts are identical in males and females at birth

  • Enlargement of the breast at birth may be evident and secretion may be produced in response to maternal hormones that cross the placenta


Functional anatomy
Functional anatomy breast

  • In female the breast remains udeveloped until puberty

  • Ovarian estrogen and progesterone initiate proliferation of the epithelial and connective tissue elements and it enlarges the breast

  • The breasts remain incompletely develop until pregnancy occurs


Functional anatomy1
Functional anatomy breast

  • Amastia – absence of the breast is rare

  • Poland’s syndrom – hypoplasia or complete absence of the breast, costal cartilage and rib defects, hypoplasia of the chest wall and brachysyndactyly


Functional anatomy2
Functional anatomy breast

  • Iatrogenically breast hypoplasia

    Induced prior to puberty:

    trauma, infection, radiation therapy



Functional anatomy4
Functional anatomy breast

  • The breast is composed of 15 to 20 lobes

  • Lobes are composed of several lobules

  • Each lobe of the breast terminates in a major duct, which opens through constricted orifice into the ampulla of the nipple






Functional anatomy8
Functional anatomy breast

  • In the early phase of the menstrual cycle, minor ducts are cord-like with small lumina

  • At the time of ovulation, with estrogen stimulation, alveolar epithelium increase, in high, duct lumina become more prominent and some secretions accumulate

  • When the hormonal stimulation decrease, the alveolar epithelium regresses



Physiology1
Physiology breast


Physiology of the breast
Physiology of the breast breast

  • Breast development and function are initiated by variety of hormonal stimuli:

    Estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, growth hormone


Phisiology of the breast
Phisiology of the breast breast

  • Estrogen initiates ductal development

  • Progesterone is responsible for differentiation of epithelium and lobular development

  • Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and postpartum period



Phisiology of the breast2
Phisiology of the breast breast

Breast changes associated with menstrual cycle:

1.Increase of DNA synthesis in ductolobular epithelium during luteal phase

2.Increse of cell deletion during the luteal phase. Concomitant vacuolization of the basal layer of the epithelium.

3.Luteal increase in the number of lobules at each ovulatory cycle.

4.Increased cellularity of the stroma and perilobular lymphocytic infiltration during premenstrual phase.

5.Premenstrual phenomenon of engorgement: increase in extracellular fluid, breast size, tension


Phisiology of the breast3
Phisiology of the breast breast

  • At the end of the menstrual cycle, there is an increase in size and density of the breast, which is followed by engorgement of the breast tissue and epithelial proliferation. With the onset of menstruation, the breast engorgement subsides and epithelial proliferation decreases


Phisiology of the breast4
Phisiology of the breast breast

Pregnancy – the breast enlarges as ductal

and lobular epithelium proliferates

First and second trimesters – ducts

branch and develop

Third trimester – fat droplets accumulate in

the alveolar epithelium and colostrum fills

the alveolar and ductal spaces

Late pregnancy – prolactin stimulates

the synthesis of milk fats and proteins


Phisiology of the breast5
Phisiology of the breast breast

Menopause – decrease in secretion of estrogen and progesterone by ovaries – involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density and the breast tissues are replaced by adipose tissues



Physiology of the breast gynecomastia
Physiology of the breast breastGynecomastia

  • Gynecomastia – enlarged breast in the male

  • Physiologic gynecomastia – occurs in:

    neonatal period

    adolescence

    senescence

    Common to each of phases: an excess of circulating estrogens in relation to circulating testosterone


Physiology of the breast gynecomastia1
Physiology of the breast breastGynecomastia

  • Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues

  • Adolescence gynecomastia – an excess of estradiol relative to testosterone

  • Senescent gynecomastia – circulating testosterone levels falls, resulting in relative hyperestrinism


Gynecomastia
Gynecomastia breast


Gynecomastia1
Gynecomastia breast


Gynecomastia2
Gynecomastia breast

Pathophysiologicmechanisms of

gynecomastia

I. Estrogen excessstates

A. Gonadalorigin

1. Truehermaphroditism

2. Gonadalstromal (nongerminal)

neoplasms of thetestis

3. Germcelltumors

(chorioncarcinoma, seminoma)


Gynecomastia3
Gynecomastia breast

B. Nontesticulartumors

1. adrenalcorticalneoplasms

2. Lung carcinoma

3. Hepatocellular carcinoma


Gynecomastia4
Gynecomastia breast

Pathophysiologic mechanisms of

gynecomastia:

C. Endocrine disorders

D. Diseases of the liver-nonalcoholic

and alcoholic cirrosis

E. Nutrition alteration states

II. Androgen deficiency states

A. Senescence


Gynecomastia5
Gynecomastia breast

B. Hypoandrogen states (hypogonadism)

1. Primary testicular failure (Klinefeltr’s

syndrome, eunuchoidal males etc)

2. Secundary testicular failure (trauma,

orchitis, cryptorchidism, irradiation

C. Renal failure

III. Drug – related (cimetidine, ketoconazole,

phenytoin, spironolactone, antineo-

plastic agents, diazepam, reserpine,

theophylline, verapamil, tricyclic

antidepressants, furosemid


Gynecomastia6
Gynecomastia breast

Treatment:

1.androgen deficiency – testosterone

administration may cause-regression

2. medications – then these are discontinued if possible

3. endocrine defects – specific therapy


Gynecomastia7
Gynecomastia breast

When gynecomastia is progressive and does not respond to other therapies, surgical therapy is considered

Breast cancer in men may also occur


Benign breast diseases
Benign breast diseases breast

ANDI - Abberations of Normal

Development and Involution -

classification of benign breast

conditions are:

1. benign breast disorders and

diseases related to the normal

process of reproductive life and

involution


Benign breast diseases1
Benign breast diseases breast

2. there is a spectrum of breast

conditions ranges from normal to

disorder to disease

3. the ANDI classification encompasses

all aspects of the breast condition,

including pathogenesis and the

degree of abnormality


ANDI breast

normal

Early reproductive lobular develop-

years (age 15-20) ment

stromal develop-

ment

nipple eversion


ANDI breast

disorder

Early reproductive Fibroadenoma

years (age 15-20) adolescent hyper-

trophy

nipple inversion


ANDI breast

disease

Early reproductive giant fibroadenoma

years (age 15-20) gigantomastia




ANDI breast

normal

Later reproductive cyclical changes

years (age 25-40) of menstruation

epithelialhyper-

plasia of pregn-

cy


ANDI breast

disorder

Later reproductive cyclical mastalgia

Years (age 25-40) nodularity

bloody nipple dis-

charge


ANDI breast

disease

Later reproductive subareolar abscess

years (age 25-40) mammary duct fis-

tula

incapacitating mas-

talgia


ANDI breast

normal

Involution lobular involution

(age 35-55) duct involution

- dilatation

- sclerosis

epithelial turnover


ANDI breast

disorder

Involution macrocystes

(age 35-55) sclerosing lesions

ductal ectasia

nipple retraction

epihelial hyperplasia


ANDI breast

disease

Involution periductal mastitis

(age 35-55) epithelial hyperplasia

with atypia


Cancer risk associated with benign breast disorders
Cancer risk associated with benign breast disorders breast

Nonproliferative lesions of the breast no

Sclerosing adenosis no

Intraductal papilloma no

Florid hyperplasia 1,5-2

Atypical lobular hyperplasia 4

Atypical ductal hyperplasia 4

Ductal involvement by cells of

atypical ductal hyperplasia 7

Lobular carcinoma in situ 10

Ductal carcinoma in situ 10


Benign breast disorders
Benign breast disorders breast

Benign breast disoreders (BBD) have

pathogenesis in hormonal events

during reproductive life. Yet the clas-

sical theories of persisting hyper-

estrogenism and luteal progestogen

deficiency have not stood up to

detailed investigation


Benign breast disorders1
Benign breast disorders breast

Daily, menstrual and seasonal dynamic

hormonal changes play important role

in BBD


Benign breast disorders2
Benign breast disorders breast

Methylxanthines, tyramines, nicotine

and physical and emotional stress are

etiological or promotional factors in the

development of BBD through

stimulating catecholamine release.

Women with BBD have higher

circulating catecholamine levels than

without BBD


Benign breast disorders3
Benign breast disorders breast

Symptoms:

Cyclical mastalgia, non cyclical

mastalgia (no relationship to the

menstrual cycle) – duration of the pain

for longer than 7 days may be

considered to be the division between

normal and disorder

Nodularity

Nipple discharge – dark green, brown,

yellow, white, serosus, bloody


Benign breast disease
Benign Breast Disease breast

Treatment:

Breast cancer must be excluded

The most effective treatment for

breast pain is exclusion of serious

pathology, reassurace and explanation

of the condition. This proves succesuful

in 85% of patients initially presenting

with breast pain


Breast benign disease
Breast benign disease breast

Drug treatments for breast pain:

Bromocriptine – dopamine agonist on the

pituiary, reduce the secretion of prolactin

Danazol – gonadotropin release inhibitor

Evening primrose oil – rich source of

gamma – linolenic acid, women with

mastalgia have reduced level

Tamoxifen – antiestrogen

Goserelin – analogue LHRH



Breast cancer hormonal risk factors
Breast cancer - hormonal risk factors breast

Increasedexposure to estrogen isassociated with anincreasedrisk for

developing breastcancer, whereasreducingexposureisthough to be protective


Breast cancer hormonal risk factors1
Breast cancer - hormonal risk factors breast

Early menarche, mulliparity

and late menopause increased risk

Moderate levels of excersise

and longer lactation period decrease risk

Full term pregnancy decrease risk

Older age at first live birth increased risk

Obesity increased risk

Alcohol consumption increased risk

Chronic consumption of fat increased risk

Anticonception pills increased risk

Postmenopausal hormone

replacement therapy increased risk


Breast cancer1
Breast cancer breast

ER – estrogen receptor

PR – progersteron receptor

+ 60-70% good responce

- 10-15% responce


Breast cancer2
Breast cancer breast

Oophorectomy, adrenalectomy, and/or

hypophysectomy, in the past, were

the primary endocrine modalities used

to treat metastatic breast cancer


Breast cancer3
Breast cancer breast

Estrogen blockers – tamoxifen

Aromatazyinhibtor – anastrazol,

letrozol

LHRH – analogue - goserelin






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