Benign Breast Diseases29.7

The Burden of Benign Breast Disease • Common condition- 9 out of 10 women attending a Breast Outpatient’s Clinic • Usually no risk of cancer • Need REASSURANCE

Learning Objectives • To understand ANDI concept • Most benign conditions – a variation of normal • Mastalgia- types, clinical features, therapy • Nipple discharge- causes, therapy

Ductolobar system • Breast: 7-10 lobes. • TDLU- terminal ductal lobular unit-functional unit - 40 • Lobe drained by ductal system leading to lactiferous sinus opens on nipple

Breast development

10-12yr 16-18yr

14-16yr

• Breast bud elevation • Growth & protrusion of nipple • Elevation of secondary areolar mound • Regression of

Hormonal Control • Estrogen – induces duct sprouting – stromal development – increased vascularity (anovulatory cycles).

• Progestrone – lobulo alveolar development.

• Prolactin - milk secretion in primed breast, • Inuslin, steroids, growth hormone -

3 Common Presentations • Lump or Lumpiness • Nipple Discharge • Breast pain or Mastalgia

The ANDI Concept • Aberration of Normal Development & Involution • Old terms like Fibroadenosis or Fibrocystic disease do not relate to clinical or histological features • Most benign disorders derive from minor aberrations of normal process of development, cyclical change and involution

Early reproductive 15-25 years Mature 25 – 40 years

Involution 35 – 55 years

Lobular development Stromal development Nipple eversion Cyclical menstrual change Epithelial hyperplasia of pregnancy

Fibroadenoma Adolescent hypertrophy Nipple inversion Cyclical Mastalgia Nodularity Discharge

Macro and Lobular microcyst involution Duct ectasia Duct involution

Nipple retraction

Mastalgia • Cyclical Pronounced Type- 40% – Cyclical pain with premenstrual exacerbation – Bilateral , diffuse – Usually with diffuse nodularity – Heaviness and feeling of increased breast size with cup size –15% volume rise • Age- young and middle aged

Pain Chart

Mastalgia • Painful nodularity for more than 1 week of menstrual cycle • Normal premenstrual discomfortreassure • Can be cyclical/non-cyclical/extramammary • Etiology– disturbance of hypothalamic control, prolactin secretion – role of estrogen receptor, deficiency of essential fatty acids, – elevation of HDL-C.

Cyclical mastalgia • Hormonal basis as relieved by Menstruation Pregnancy and lactation Tamoxifen and Centchroman

Increased Estrogenic, Prolactin response – Basal hormones normal Cancer risk -

Mastalgia • Non-Cyclical Pain- 27% – – – –

No relation to menstrual cycle on Pain chart Unilateral or bilateral Subareolar or Outer Upper Quadrant Trigger point pain Tietze’s syndrome- 11% Trauma (post biopsy) – 8% Cancer 0.5% Musculo-skeletal- 9%

Management of Mastalgia • • • • • • • • •

Evaluation for lump – EXCLUDE Cancer Reassure- 85% will be relieved Pain Chart for 2 menstrual cycles Life style modification- support bra- tight in day light at night, exercise Drug Therapy Anti-inflammatory gel Local Anaesthetic with Steroid Injection for trigger point pain Excision of painful nodule Reflex therapy

Drug Therapy for Mastalgia • Drug of Choice-Tamoxifen- 10 mg daily for 3 months – Response- 98% for cyclical, 56% noncyclical – Side effects 50% - hot flashes, vaginal discharge

Drug Therapy of Mastalgia Danazol- 100 – 300 mg Response 70% good control Side effects – 25% wt gain, hair growth,

• Evening Primrose oil- 6 capsules – Response 2/3rd good control – Side effects minimal- 4% – No benefit over placebo (Srivastava et al, Breast 2007)

Treatment • Bromocriptine - 2.5 mg/d. prolactin lowering agent. – Side effects - nausea ,vomiting, dizziness

Br J clin pract1986;40:326 Br J surg 1978;65:724

Meta-analysis of RCT on Mastalgia Brom oc ripti ne • Wei gh ted mea n differ ence in the p ai n scor e in fa vo ur of Bromocr ipt ine was – 16.3 1( 95 % C.I. −26.3 5 to −6.2 7) • RR of pain res pon se 5.2 9( 95% C.I., 2.5 6 to 10. 89 )

Forest Plot on Bromocriptine vs Placebo

Tam oxi fen RR of p ain r el ie f = 1 .92 (95% CI 1 .4 2 to 2 .58)

Dan az ol si gnifi ca nt be nefi t in th e ameli orati on o f mas tal gia,wi th a mea n pain scor e di ffer en ce – 20.2 3(9 5% C.I. –2 8. 12 to – 12.3 4).

Forest Plot on Tamoxifen vs Placebo

Ev ening p rim ros e oil • Ev eni ng p rim ros e oil d id not offe r a ny ad va nt age ove r pla ce bo in pai n re li ef , me an p ain scor e d if fere nc e –2. 78 ( 95% C.I . –7 .97 to 2.4 0)

Centchroman/ Ormeloxifene Background • Synthesized at the Central Drug Research Institute, Lucknow • Marketted in India since 1992 • Included in the National Family Welfare Programme in 1995 as an OCP

Randomized study Aims and Objectives

•

To investigate the role of Centchroman in regression of fibroadenoma measured by serial Ultrasound and Clinical Examination.

•

To evaluate the effectiveness of Centchroman in control of mastalgia compared to Danazol.

Materials and Methods (Mastalgia) Moderate to severe mastalgia Breast pain chart and USG pelvis Randomization Centchroman 30 mg alt. Day for 12 weeks

Danazol 100 mg daily for12 weeks

Follow up at 24 weeks

Follow up at 24 weeks

Effect of Centchroman vs. Danazol in mastalgia

7 6

VAS

5 4 3 2 1 0 0

2

4

6

8

10

12

14

16

18

Weeks Danazol

Centchroman

20

22

24

Effect of Centchroman vs. Danazol on Visual Analogue Score in Cyclical Mastalgia:

7

Median VAS

6 5 4 3 2 1 0 0

2

4

6

8

10

12

14

16

Weeks Danazol

Centchroman

18

20

22

24

Effect of Centchroman vs. Danazol on Visual Analogue Score in non-cyclical Mastalgia 8 7 Median VAS

6 5 4 3 2 1 0 0

2

4

6

8 10 12 14 16 18 20 22 24 Weeks

Danazol

Centchroman

Effect of Centchroman vs. Danazol on nodularity

% Nodularity

70 60 50 40 30 20 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Weeks Danazol

Centchroman

Effect of Centchroman vs. Danazol on tenderness in mastalgia

% patients with tenderness

90 80 70 60 50

Danazol

40

Centchroman

30 20 10 0 0 2 4

6 8 10 12 14 16 18 20 22 24 Week

Nipple discharge • 5% of cases • 95%of cases benign cause • Spontaneous & bloody discharge single/multiple ducts - significant. • Assess for lump • <10% bloody discharges are malignant • Cytology-low sensitivity for cancer - 3545%

Causes of Nipple Discharge Blood

Ductal hyperplasia and papilloma, duct ectasia, pregnancy, cancer

Serous or Watery

Ductal hyperplasia, duct ectasia

Coloured

Duct ectasia, Cyst

Milk

Physiological, Galactorrhoea with Prolactin secreting lesions

Causes • Physiological –small quantity, multiple duct, varies in color, noticed after warm bath or manipulation. • Intra ductal papilloma-major sub-areolar duct,serous or sanguineous discharge, mass felt 1/3rd of cases; microdochectomy preferred. • Multiple papillomas-10% cases.same duct,nipple discharge is less common

Causes contd. • Juvenile papillomatosis-10-44 yrs age, increased risk of cancer(10%). Peripheral distribution. Wide local excision. • Pregnancy –bloody discharge physiological due to increased hypervascularity. • Galactorrhoea –bilateral copius mult.duct discharge not associated with pregnancy/lactation. Take drug h/o, S.prolactinlevel. Bromocriptine/cabergoline -effective treatment

Investigations • USG-demonstrates dilated sub areolar ducts.75%of lesions seen.85%accurate. • Mammography –age >35yrs, presence of lump. • Ductography –filling defect /cut off in cases of papilloma/cancer (60%sensitivity) • Indicated for pt with minimal

Surgery unit 1

Duct ectasia • Process of involution • Age related,42-65 yrs. • Nipple retraction, cheesy toothpaste like nipple discharge. • Lesions usually sterile. • Characteristic coarse calcification on mammogram.

Periductal mastitis • Episodes of periareolar inflammation +/- mass, periareolar abscess, mammary duct fistula. • Affects 18-48 yr age. • Purulent nipple discharge with retraction. • Pain –non cyclical, eczema of areola. • Anaerobes isolated 80-100%cases. • Smoking –damage to duct wall,

Management • Antibiotics – anaerobes/staph.cover.Initially and for recurrent attacks(2 wk course). • Aspiration of pus/conservative drainage • Surgery-nipple discharge/ ,retraction subareolar abscess-(initial antibiotics, surgery after 6weeks) fistula recurrence after prev.Sx

Radical duct excision • Peri-areolar incision 1/3rd circumference. • Plane deep to sub. cut venous plexus. • Undersurface of nipple bared completely • Hemostats behind ductal cone 3&9 o’clock. • Ignore peripheral dilated ducts. • Remove 3 cm cone of breast tissue

Fistulectomy • Remove the nipple opening of duct • Heal by granulation. (Atkins BMJ,1955) • Probe the fistula and emerge from nipple. • Radial elliptical incision 1cm wide. • Primary closure under antibiotic cover.

Summary • Benign breast conditions are very common • Usually need simple reassurance after excluding cancer • Most conditions can be managed at Primary care level

HRT and Benign breast disease • Increased epithelial hyperplasia of ducts and lobules ± Atypia • Increased Mastalgia • Growth of Papillomatosis • Increased cyst formation • Growth of Fibrodenoma

Mucocele of breast

Lipoma • Avg.45 yrs • Smooth lobulated, mobile mass • PSEUDOLIPOMA-cancer shortens Cooper’s ligaments, fat lobules bunched up • USG/mammogram-circumscribed translucent area, compressing surroundings • When in doubt –excise

Filariasis of breast

Risk of Breast cancer in BBD No risk

Simple cyst, duct ectasia, papilloma, hyperplasia without atypia

Relative risk 1.5 to 2 Relative risk 4 to 5 Relative risk 8 t 10

Moderate hyperplasia, papillomatosis Atypical ductal or lobular hyperplasia Lobular carcinoma in situ

Triple Assessment Careful history – hormones, relation with menstrual cycle, pregnancy or lactation 1.Clinical Breast Examination 2.Imaging- Ultrasound / Mammography 3.Fine needle aspiration cytology(FNAC) or Core Biopsy Sensitivity for a lump = 100%

Galactocele

Aspiration

Galactocoele • Cyst filled with milk • Follows abrupt artificial /natural (wksmonths) cessation of lactation • Pre existing cyst connects with ductal system & fills with milk • Painless, smooth, mobile swelling near areola • Cured with single aspiration • USG preferred imaging

Breast Cysts True cysts– – ANDI-micro/macro cysts – Juvenile cysts – Secondary cysts-galactocele, fat necrosis, hematoma, implant related – Papillary tumors To differentiate from- duct ectasia/periductal mastitis,phylloides,carcinoma,hydati

The Lady with a Lump • DISCRETE LUMP – Fibroadenoma – Phyllodes tumour – Nipple Adenoma and Papilloma – Breast cyst and Galactocele ILL DEFINED LUMP Cyclical Nodularity Fat necrosis NORMAL STRUCTURES Prominent Rib Intramammary lymph node Prominent fat lobule Edge of Breast or Biopsy scar

Management • USG, mammogram >35yrs. • Needle aspiration – Bloody then cytology – Residual-USG guided aspiration

• Complex cysts with solid component not to be aspirated. • Mammogram-a week after intervention to assess rest of parenchyma. • Persistent mass/blood stained fluid /recurrent–excise.

Causes • 7-10% of women develop cysts in lifetime • Etiology unclear, part of involution • Role of hyperestrogen, increased prolactin • Role of HRT • More in left breast, upper outer quadrant. • Ages 40-50yrs, elderly tend to be cancer

Pathogenesis • Apocrine epithelium of terminal ductal lobular unit • Excess secretion &osmotic effectsmicrocyst • Macrocysts-type1-active-ICF like type2-flat epitheliumECFlike

Treatment Surgery for spontaneous single duct discharge with1. bloody character 2.persistent >2/week 3.age >40 4.presence of lump Age> 45, with mult.duct discharge – radical duct excision.