THE BREAST

Introduction

Modified sweat glands.Lobes and lobules of gland in fat tissue stroma.Ducts emerge from acini of glandsSmaller ducts join to form lactiferous

ductsLactiferous ducts merge just beneath

the nipple to form a lactiferous sinus.Then individually open on nipple

Figure 23-1 Anatomic origins of common breast lesions.

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Normal Breast,Luminal (milk producing cells) and myoepithelial cells)

Disorders

Congenital Aplasia – turners, Juvenile

hypertrophy,Macromastia Inflammatory

Infections acute/chronic – Trauma Fat necrosis

Duct ectasia discharge, sinus Fibrocystic disease – common – painful

lumps Neoplastic

Benign - Fibroadenoma Malignant – Ca

Breast Symptoms

Pain(Most common symptom)Most are benign. Palpable Mass

Nipple discharge

Palpable masses 2nd most common breast symptom. A breast

mass becomes palpable when >2cm Distinguish a palpable mass from vague

nodularities or lumpinessLesions includes: Invasive carcinoma, fibroadenomas and cysts. 10% of palpable masses are malignant in

under 40 yr olds compared to 60 % malignancy rate for palpable masses in over 54 yr .olds

50 % of carcinomas arise in upper outer quadrant.20% in central quadrant and 10% each in the other quadrants

Figure 19-23 Representation of the findings in a series of women seeking evaluation of apparent breast "lumps."

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Nipple discharge

Note that galactorrhea is not associated with malignancies

Serous or bloody nipple discharge may be seen in a small percentage of breast cancers

The older the age, the higher the risk of a malignancy in a patient with bloody or serous discharge.

Mastitis Inflammation of the mammary gland Causes : 1. breast feeding (Acute mastitis) 2. Periductal mastitis 3. Mamary Duct EctasiaB 1. Breast feeding (Acute mastitis)A blocked milk duct Cracked or damaged skin or tissue around

the nipple Signs :red, hot, painful, or inflamed

breasts with flu-like symptoms such as headache, nausea, high temperature

• Staph aureus • Strept.

Mastitis

Periductal mastitis (Zuska disease,recurent sub -areolar abscess)

Recurrent sub-areolar abscess Painful mass that resembles infection Not associated with lactation 90% of patients are smokers Keratinizing squamous metaplasia of

the nipple ducts. ? Vitamin A deficiency, Toxic

metabolites of tobacco.

Periductal mastitis

Mammary duct ectasia

Nonbacterial chronic inflammation of the breast associated with inspissation of breast secretions in the main excretory ducts.

Multiparous women Ductal dilation with ductal rupture

leads to reactive changes in the surrounding breast substance.

40- 50 year old women Not Associated with smoking.

Fat Necrosis Trauma, Prior surgical intervention A zone of necrotic fat cells surrounded

by lipid-filled macrophages and an intense neutrophilic infiltration, foreign body giant cells, calcium salts.

Eventually the focus is replaced by scar tissue or is encysted and walled off by collagenous tissue

Match the following

Periductal fibrosis Acute mastitis Fat Necrosis

Smoking Breast feeding Trauma

Fibrocystic Changes Non proliferative type

Fibrosis, Cyst formation, apocrine metaplasia,

Proliferative type Papilloma(s), florid sclerosing adenosis, moderate to florid ductal hyperplasia,

Risk of malignancy increases from simple fibrocystic change to fibrocystic change with atypical hyperplasia

Family history of breast cancer increases the risk by up to 10%

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Fibrocystic Changes

Symptoms and Signs Breast pain (mastodynia) and/or tenderness

is observed in the majority of patients. Mastodynia may start a few days or 1 to 2 weeks

before menstruation; it usually eases or subsides with the onset of or during menses

Nipple discharge is spontaneous or secretion can be expelled from the nipple

Diffuse lumpy feeling in the breast .

Fibroadenoma Firm, noncancerous tumor of the

breast. It is round, painless, feels firm

and rubbery, and can be easily moved around.

Peak age:20-30 Rapidly grow to a large size Present with Palpable mass or

mammographic density Malignant transformation rare

Fibroadenoma

Fibroadenomas may enlarge during late menstrual period and tends to calcify or regress by menopause

Lobular stromal cells are the neoplastic component in fibro-adenomas

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Phyllodes tumorCystosarcoma phyllodes• epithelial-stromal neoplasms with

dominating stroma and leaf-like structure

• Most are benign lesions.• 15% are malignant.• 0.3% of all breast tumors• 30% recurrence; 10% metastasis• Age: older than with FA (average 45)• Well defined, uncalcified, lobulated,

round or oval• Commonly with thin irregular cystic

spaces

Quiz A 30 year old woman complained that

she has noticed a firm ,painless , freely mobile mass located in the upper –outer quadrant of her left breast. The mass increases in size towards the end of her menstrual flow. Which of the following is the most likely diagnosis?

A. MelanomaB. FibroadenomaC. Fibrocystic changeD. Breast cancer

INTRADUCTAL PAPILLOMA: Benign solitary lesions within the

ducts. EPIDEMIOLOGY: Middle-aged and older

women. SYMPTOMS: Serous or Bloody Nipple discharge,

nipple retraction. Lump beneath nipple. papillary clonal proliferations of duct

epithelia cells composed of multiple branching papillae

Benign and are not the precursors of papillary carcinoma

TREATMENT: Surgical excision.

Breast Carcinoma

20% of all cancers in women

Commonest cause of death - 35-55y

1 in 8 women in US Less incidence in Asia Majority of cancers

arise in the ducts. Very rare before age

25

Risk Factors:Female ..!, Age, Obesity, high

fat ,low fibre diet Maternal relative with breast cancer. Longer reproductive span. Nulliparity, Oral contraceptivesLater age at first pregnancy. Atypical epithelial hyperplasia. Previous breast cancer/Endometrial

Ca. Geographic factors –Western

countriesBRCA1 and BRCA2 genesPostmenopausal hormone

replacement

Etiology of Breast Carcinoma:

Genetics/Hereditary BRCA-1(Also ovarian

cancer,Pancreatic cancer)

BRCA-2(Also pancreatic cancer)

BRCA-1 and 2 have an autosomal dominant pattern of inheritance.

Li Fraumeni syndrome P53 Her-2/neu, c-erB2

Sporadic Breast carcinoma Majority of breast CA is sporadic Hormonally and environmental

factors Most are ER positive and occur

in Postmenopausal women.

Breast Carcinoma

Epithelial Non-invasive

Ductal carcinoma in situ (DCIS) Lobular carcinoma in situ (LCIS)

Invasive Ductal (85%) Lobular (1%) Mucinous (5%) Papillary (<5%) Medullary (<5%)

Mixed Connective tissue and Epithelial

Miscellaneous

CLASSIFICATIONAll Breast CA arise from epithelial cells

in the TDLU>90% are adenocarcinomas and are

divided into:1.1. Carcinoma in situ(DCIS,LCIS) Intact basement membrane Carcinoma is limited to the lobule or

ducts22. Invasive carcinoma Basement membrane is breached Tissue invasion and metastasis is

possible.

CLASSIFICATION

The classification into ductal or Lobular refers to the histological appearance and the biologic properties of the tumor rather than to the cell of origin.

Lobular carcinoma refers to a distinct subtype while the term Ductal refers to any histological type that is not otherwise specified.

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Direct precursor of invasive ductal carcinoma• Visible on mamography because of calcification• Most often picked up via mamography• Clonal proliferation of cells in the ducts and lobules

limited by basement membrane.• Five subtypes:• Comedone, Solid, cribriform, papillary and micro

papillary• Mastectomy is usually curative(95%)• Incidence of DCIS increases with increase uptake of

mamographic screening in any population.

DUCTAL CARCINOMAIN-SITU

DUCTAL CARCINOMAIN-SITU

Paget disease of the nipple Rare manifestation of breast cancer (1%

to 4% of cases) Unilateral erythematous eruption with

scaly crust and Pruritus. Malignant cells (Paget cells) extend from

DCIS via the lactiferous sinuses, into nipple skin without crossing the basement membrane.

60% of women with the lesion would have an underlying mass and invasive cancer.

Pagets breast

Pagets Disease (Epidermal invasion)

Comedo type DCIS

Large central zones of necrosis with calcified debris.

Also note the surrunding intense stromal fibrosis

Mammographic calcifications

LOBULAR CARCINOMA IN SITU Incidental biopsy finding, No calcifications or stromal

reactions that produce mammographic densities.

Incidence is not affected by mamographic screening.

Bilateral in 20% to 40% of cases, compared with 10% to 20% of cases of DCIS.

LCIS is more common in young women, 80% to 90% of cases occurring before menopause.

LOBULAR CARCINOMA IN SITU

The cells of LCIS and invasive lobular carcinoma are identical.

Loss of expression of E-cadherin

LCIS

DCIS/LCIS

DCIS LCIS

No loss of E-Cadherin May be palpable,

calcification or densities on Mammography

Less bilateral =>Invasive ductal CA

Loss of E-Cadherin Detection by

mammography is low

More bilateral =>Invasive Lobular

CA

Younger age

INVASIVE BREAST CARCINOMA

INVASIVE BREAST CARCINOMA Without mammographic screening,

invasive carcinoma presents as a palpable mass.

Palpable tumors are associated with axillary lymph node metastases in over 50% of patients.

Larger carcinomas may be fixed to the chest wall or cause dimpling of the skin=> Nipple retraction

Lymphedema and thickening of the skin may occur as a result of lymphatic blockade Leading to peau d'orange.

Inflammatory carcinoma refers to tumors that present with a swollen, erythematosus breast. They tend to have poor prognosis.(Commoner with African ancestry)

BREAST CANCER

• Most common histologic type• 70 - 80% of all breast cancer• Diagnosis of exclusion• Breast cancer NOS or NST.

Invasive Ductal Carcinoma

BREAST CANCER

•Grossly forms hard and stellate mass

• Used to be call “scirrhous” ca

• Typically metastasize to bone, liver and lung

Invasive Ductal Carcinoma

Well differentated Invasive ductal cancer

Poorly differentiated Invasive Ductal Cancer

Invasive Lobular Carcinoma• Composed of small cells with linear arrangement

• Commonly forms multifocal and multicentric lesions

• Metastasize to meninges(carcinoma meningitis), serosal

surfaces, ovaries and retroperitoneum.

E-Cadherin mutationsSignet ring cells.

Invasive Lobular CarcinomaIndian file pattern

BREAST CANCER

Tubular Carcinoma

• Variant of ductal carcinoma• Usually small lesion detected by mammogram• 5 - 10% of all breast cancers• Better prognosis• Small tubules composed of neoplastic cells with low grade nuclei.

BREAST CANCER

Mucinous Carcinoma

• 5% of all breast cancers• Older age group• Abundant accumulation of extracellular mucin• Low grade tumor, grows slowly

BREAST CANCER

Medullary Carcinoma• 5% of all breast carcinoma

• Younger age group• Well circumscribed mass• Sheaths of tumor cells with high nuclear grade and intense lymphoplasmacytic infiltrateNo Hormone receptors ,no over expression of her-2 neu. (similar to basal type cancers) better prognosis than NST

Hormone receptors and Her -2/neu

Hormone receptor positive tumors have good response to anti-estrogen therapy such as Tamoxifen but have poor response to chemotherapy.

Tumors arising from the basal group of cells are usually negative for ER,PR and HER-2 /Neu(Triple Negative).This tumors tend to have good prognosis.

Peu d ‘orange

Breast Carcinoma - Schirrous

Medullary Carcinoma: Large soft

Stage 1

Tumor < 2.0 cm in greatest dimension

No nodal involvement (N0)

No metastases (M0)

Stage II

Tumor > 2.0 < 5 cm

or Ipsilateral

axillary lymph node (N1)

No Metastasis (M0)

Stage III

Tumor > 5 cm (T3)or ipsilateral axillary lymph nodes

fixed to each other or other structures (N2)

involvement of ipsilateral internal mammary nodes (N3)

Inflammatory carcinoma (T4d)

Stage IV (Metastatic breast cancer)

Any T Any N Metastasis (M1)

PROGNOSTIC FACTORS

• Examination of the primary carcinoma and the axillary lymph nodes. correlated with survival : Invasive carcinoma versus in situ disease.

Cure is possible when the carcinoma has not crossed the basement membrane.

Distant metastases. Cure is rare in the presence of distant metastasis.

Lymph node metastases. Axillary lymph node status (sentinel biopsy) .Most Important prognostic factor for non metastatic disease.

SENTINEL LYMPH NODE

PROGNOSTIC FACTORS

Tumor size. Size of an invasive carcinoma is

the second most important prognostic factor for non metastatic disease.

Risk of axillary lymph node metastases increases with the size of the primary tumor carcinomas <1 cm in size have a 10-year survival rate of over 90%, this drops to 77% survival for cancers >2 cm.Mammographically detected cancers are smaller and less likely to have metastasized.

PROGNOSTIC AND PREDICTIVE FACTORS

Locally advanced disease. Large carcinomas with invasion into skin and muscle are usually beyond surgical salvage.

Inflammatory carcinoma. Presenting with swelling and skin

thickening due to dermal lymphatic involvement have a poor prognosis.

3-year survival rate is only 3% to 10%.

Higher incidence with African descent and younger women

Other prognostic factors

Histology subtypes

Allsubtypes(Tubular,Mucinous,medullary,Lobular,papillary) have a better prognosis compared to the NST or invasive ductal carcinoma.

30 year year survival rate of >60% COMPARED TO <30% OF DUCTAL TUMORS.

Hormone receptors and Her -2/neu Progesterone, Estrogen and Over-

expression of Human epidermal growth factor receptors( HER-2 /neu)

Well differentiated/low grade tumors usually express ER,PR and do not over express HER-2 /neu

Poorly differentiated /high grade tumors do not express ER/PR but usually over express HER-2/neu.

Demonstrated by Immunoperoxidase special stain.

Response to hormonal therapy or targeted Therapy Estrogen and Progesterone receptor

positive tumors have good response to hormonal manipulation.

Tumors that are HER 2/neu positive have shown good response to Trastuzumab (Herceptin)