Benign Breast Disease

Introduction:

• Benign breast condition are practically a universal phenomena among women.
• It is more common than breast cancer but difficult to differentiate it from cancer although it accounts for about 90% of clinical presentation related to the breast
• In any women presenting with a breast lump it is important to try to differentiate those that are benign from those that may be malignant.
• Incorrect diagnosis and inappropriate treatment is associated with significant morbidity
• Triple assessment approach (history & clinical examination, imaging and pathological studies) are important to reach the final diagnosis

Different between Benign & Malignant:

1. By physical examination: 

• Generally:

	Benign	Malignant
Consistency	Soft or rubbery	Hard or firm
Skin manifestation	Absent	Present (advance stage)

• Exception:

Benign lesion that mimic cancer	Cancer lesion that mimic benign
- Radial scar - Traumatic fat necrosis - Diabetic fibrous mastopathy - Granulomatous mastitis	- Lobular carcinoma in situ - Medullary carcinoma - Tubular carcinoma - Phylloid tumour

Clinical Picture:

1. Painless breast lump (36%)
2. Painful lump or lumpiness (33%)
3. Breast pain alone (17.5%)
4. Nipple discharge (5%)
5. Nipple retraction (3%)
6. Swelling or inflammation (1%)

Evaluation:

• The triple assessment approach in benign breast disease are:

1. History taking and clinical examination (see gynecology chapter)
2. Imaging→ ❶ Ultrasound ❷ Mammography
3. Pathological studies→ ❶ Fine needle aspiration cytology (FNAC) ❷ Core biopsy ❸ Open biopsy

Etiology:

• Most benign conditions arise on the basis of dynamic changes which occur in the breast through the 3 main periods of reproductive life
• These changes are known as Abberation of Normal Development and Involution (ANDI)

1. Breast Development→ Disorder of breat development in early reproductive life
2. Cyclic Activity→ Disorder of breast condition in mature reproductive life, regular changes in relation to menstrual cycle, pregnancy doubling the breast weight at term
3. Involution→ Disorder of breast condition in late reproductive life, the breast stroma is replaced by fat, focal change of normal epithelium to sweat gland epithelium (apocrine metaplasia), increase number of gland (adenosis) and increase number of cell lining (hyperplasia)

• Abberation of Normal Development and Involution (ANDI):

Age	Normal Process	Aberration
< 25	Breast Development -Lobular -Stromal -Nipple evertion	Fibroadenoma (Giant fibroadenoma) Juvenile hypertrophy (Giagantomastia) Nipple inversion (subareolar abcess/ Mammary duct fistula)
25 – 40	Cyclic Activity ( regular changes in relation to menstrual cycle) Epithelial hyperplasia of pregnancy	Cyclic mastalgia (incapacitating mastalgia) Cyclic nodularity (diffuse or focal) Bloody nipple discharge
35 – 55	Involution -Lobular -Stromal -Ductal (dilatation) -Ductal (sclerosis) -Epithelial turnover	Macrocysts Sclerosing lesions Duct ectasia (periductal mastitis) Nipple retraction Epithelial hyperplasia (with atypia)

(1) Disorder of Breast Development in Early Reproductive Life
Juvenile Hypertrophy	Fibroadenoma
- Excessive breast enlargement during puberty - Overgrowth of periductal connective tissue, increase number of ducts, no lobule formation - No endocrine abnormality - Treatment: Reduction mammaoplasty	- Most common benign tumours - Occur at any time of puberty, but occur most frequent in the third decade - Painless, well circumscribed, freely movable tumours with a rounded lobulated or discoid configuration - Multiple in 10 – 15% and can become quite large - No increased risk in relation to breast cancer - Treatment: Remove fibroadenomas if >3 cm

(2) Disorder of Breast Condition in Mature Reproductive Life
Mastalgia	Nodularity
a) Cyclical Mastalgia - Heightened awareness or pain - Related to menstrual cycle - Etiology: Hormonal, water retention, neurosis, essential fatty acids - Treatment: 1. Exclude cancer 2. Reassure (proper fitting bra, reduce caffeine intake, drink soy milk) 3. Drugs (1st:Gamolenic acid-GLA, 2nd:Danazol, 3rd:Bromocriptine, 4th:Tamoxifen/LHRH) b) Non-Cyclical Mastalgia - Breast pain not related to menstrual cycle -Classification: Chest wall, true breast, non breast -Treatment: 1. Exclude specific cause 2. Simple Analgesic or NSAIDS 3. Steroid or Local Anaesthesia	a) Generalised Nodularity - Breast are normally nodular b) Focal Nodularity - Most common cause of breast lump - Up to the age of 50 -Etiology: Localised fibrosis, adenosis, microcyst or apocrine change. It also may be due to normal breast involution - Management: 1. Clinical examination 2. Mammography for patient > 40 years 3. Biopsy if suspicious 4. Reassured and discharged if no abnormality is found

(3) Disorder of Breast Condition in Late Reproductive Life
Macrocyst	Epithelial Hyperplasia
- Most common dominant lump in patient age 35- 50 years - Clinical presentation: May be silent or painful, may be palpable or only seen on ultrasound or mammography, may be single(often) or multiple and may be associated with nipple discharge - Management: 1. Mammography for patient > 40 years 2. Aspirate the fluid with 21g needle 3. Cystology study if evenly bloodstained or mass persists 4. Review after 3 – 6 weeks 5. Cyst which rapidly or persistently refill should be excised	- An increase in the number of epithelial cell layers lining the terminal duct lobular unit - Previously known as epitheliosis or papilomatous Pathology: Mild→ No increased risk, Moderate/florid changes without atypia→ (1.5 -2), Atypical hyperplasia→ moderate risk (4-5). Strong interaction between atypia and family history -Clinical presentation: Lumps, nipple discharge, screen detected -Investigation: FNAC→ atypical cells, mammogram→ architectural distortion, microcalcification - Treatment: 1. Moderate and florid hyperplasia→ no follow-up 2. Atypical hyperplasia→ clinical and mammographic surveillance, mastectomy with reconstruction
Sclerosis	Duct Ectasia
- Sclerosis adenosis and radial scars are associated with distortion of the terminal duct lobular unit - Complex sclerosing lesions are associated with a significant amount of epithelial hyperplasia -Some debate about radial scars as precursors of invasive tubular necrosis Management: 1. Excision biopsy if often required to make a definitive diagnosis 2. No follow-up required unless associated with significant degree of epithelial hyperplasia	-Ducts dilate and shorten -Contain inspissated (thick) material -Minimal inflammation -Clinical presentation: Presents with nipple discharge, slit-like nipple retraction or a mass -Treatment: Troublesome discharge→ total duct excision

Classification:

• There are now two different classifications that are used:

Clinical Classification:

Pathological Classification:

(1) Physiological swelling and tenderness→ it may be mammary dysplasia/cystic mastopathy (normally occur during premenstrual phase and resolve during menstrual phase) and premature thelarche  (2) Nodularity→ hormonally-mediated change with lumpiness of the breast, bilateral symmetrical change are rarely pathology, asymmetrical change need to be review after 1 or 2 menstrual cycle (3) Mastalgia (Breast pain)→ not usually associated with malignancy, it may be cyclic or non-cyclic pain (4) Dominant or palpable breast lumps→ most benign lumps are either cyst or fibroadenoma (5) Nipple discharge→ it may be physiological, duct papilloma, duct ectasia, periductal mastitis, cancer and galactorrhoea (hormonal imbalance) (6) Breast infection and inflammation→ usually associated with lactation (Puerperal Mastitis) or without lactation (often associated with diabetes and immune compromise)

(1) Non-proliferative disorders→ no increased risk, the specific lesions: ❶ Fibrocytic changes, ❷ Fibrocystic disease, ❸ Duct ectasia, ❹ Solitary papillomas, ❺ Simple fibroadenomas, ❻ Mastitis or breast disease, ❼ Galactocele and ❽ Fat necrosis (2) Proliferative disorders without atypia→ mild to moderate increase risk:   (3) Atypical hyperplasia→ substantial increase in risk, the specific lesions: ❶ Ductal hyperplasia, ❷ Atypical hyperplasia, ❸ Complex Fibroadenomas, ❹ Sclerosing adenosis, ❺ Radial scars

Pathology:

Fibrocystic Breast Disease:	Fibrocystic breast change:
- Most benign breast condition - Incidence-varying, related to age: ❶Menstruating year- 20% ❷30 - 50% in premenopausal years - Synonyms: ❶Mammary dysplasia  ❷Cystic disease ❸Cyclic mastopathy ❹Cystic hyperplasia	- > 20% of premenopausal women - Discomfort, cysts - Treatment rarely required - More likely to not detect a developing cancer

Pathophysiology of Fibrocystic Disease:

• Hormonal basis and Methylexanthiones 

Hormonal Basis		Methylexanthiones
(1) Estrogen & progesterone	(2) Prolactin	- Increased intake of coffee, tea, cold drinks chocolate is associated with development of FDP
- Estrogen predominant over progesterone - Corpus luteum deficiency/anovulation in 70% - Patients with Pre Menstrual Tension Syndrome more likely to develop FBD - Luteal phase is shortened - Progesterone level decreased to 1/3 of normal	- Levels are increased in 1/3 of women with FDB - Probably due to estrogen dominance on pituitary
	(3) Thyroid
	- Suboptimal levels sensitize mammary epithelium to prolactin stimulation