Carcinoma breast

Etiology Commoner in western After middle age Familial in 5% Mutation of tumour suppressor genes 1. BRCA1-located in longarm of chromosome17 2. BRCA2-located in longarm of chromosone13 Li-Fraumens syndrome is autosomal dominant condition in breast cancer inheritance Diet low in phytoestrogens and high alcohol Commoner in nulliparous.obese women-(contd)

Carcinoma breast

Etiology Early menarchy and late menopause Early childbearing and breastfeeding reduces 3-5 times risk when first degree relatives have Benign conditons as atypia,hyperplasia,epitheliosis

Carcinoma breast

Pathology Lactiferous duct-ductal ca. Lobules-lobular ca.(10%) Both may be of insitu or invasive Mainly unilateral (2-5% bilateral) Unifocal or multifocal Multifocaltumour tissue within the same quadrant at multiple foci Multicentric---tumour tissue within the same breast but different quadrant

Normal anatomy

Lobular ca insitu

Invasive lobular

Ductal ca.in situ

Invasive ductal ca.

DCIS

DCIS

Intra-ductal ca. without any invasion into the basement membrane is 5-20% common. The histological variants are Solid Comedo(central necrosis-fast growing) Cribriform Papillary Risk of lymphnode spread is negligible.so axillary dissection is not necessary.

DCIS

SOLID

CRIBRIFORM

DCIS

PAPILLARY

COMEDO

Invasive ca. (adenocarcinoma)

Histological variants 1.infiltrating ductal (75%) 2.infiltrating lobular (5-10%) 3.tubular 4.medullary 5.mucinous or colloid

Panel A: Low power view of a well differentiated infiltrating ductal carcinoma shows tumor cells which infiltrate the stroma as solid nests and glands. Panel B: High power view demonstrates relatively uniform nuclei with no evidence of mitotic activity

Panel A: Low power view of an infiltrating lobular breast carcinoma shows small tumor cells that infiltrate the stroma singly and in a single file pattern. Panel B: High power view demonstrates that the tumor cells are relatively small and uniform in appearance

medullary

Panel A: Low power view of a medullary breast carcinoma shows that the tumor has a well circumscribed border. Panel B: High power view demonstrates that the tumor cells grow in a syncytial pattern and have marked nuclear atypia. A prominent lymphoplasmacytic infiltrate is also present.

tubular

Panel A: Low power view of a tubular breast carcinoma shows that the tumor is composed of well formed glands or tubules that invade the mammary stroma. Panel B: High power view demonstrates that the tubules are composed of columnar cells with relatively uniform nuclei. Many of the cells show "snouts" of eosinophilic cytoplasm at their lumenal ends

mucinous

Panel A: Low power view of a mucinous breast carcinoma shows small nests of tumor cells dispersed in large pools of extracellular mucous. Panel B: High power view demonstrates that the nests are composed of cells with relatively uniform, low grade nuclei

Invasive ductal ca.

Macroscopic types Scirrhous ca.60%-common,hard,whitish,noncapsulated,irregular with cartilagenous consistency.it contains malignant cells with stroma.(cuts like an unripe pear) Medullary ca.also called encephaloid(soft),contains malignant cells with dispersed lymphocytes Inflammatory ca, or lactating ca,or mastitis carcinomatosismost malignant,2%,seen in lactating or pregnant women,mimics acute mastitis because of short duration,pain,warmth and tenderness contd.

Invasive ductal ca.

Inflam.ca. is rapidly progressive,short duration,involving whole breast with Peau d orange,often extending to the skin of chest wall also Rapid metastasis to chest wall,lung,bone. It is always stage 4 Total count is normal Biopsy FNAC undifferentiated cell seen Treated by external radiotherapy and chemotherapy-worst prognosis

Mastitis carcinomatosis

Mimics acute mastitis

IBC is highly angiogenic and angioinvasive

Invasive ductal ca.

Colloid ca.produces abundant mucin Pagets disease of the nipple -superficial manifestation of an intraductal ca.,malignancy spreads within duct upto the skin of nipple and down into the substance of breast,mimics eczema of nipple and areola.

Pagets disease

Pagets disease of the nipple

Pagets 1.unilateral 2.distinct edges 3.itching absent 4.menopausal women 5.vesicles absent 6.nipple flattened or destroyed 7.firm 8.underlying lump is palpable

Eczema Bilateral Indistinct Present Lactating women Present Nipple usually intact

Soft No lump

Clinical presentation of ca.br

Lump(hard,painless), Ulceration fungation Axillary LN ,supraclivicular LN Chest pain,haemoptysis Bone pain,tenderness,pathological fracture Pleural effusion,ascites Liver secondaries,ovarian tumours

Clinical presentation of ca.br

Cutaneous manifestaions Peau d orange due to obstruction of dermal lymphatics,openings of the sebaceous glands and hair follicles get buried in the edema Dimpling of skin-infiltraion of ligts.of Cooper Retraction of nipple due to involvement of lactiferous ducts. Ulceration,discharge from nipple,areola Cancer-en-cuirasse-skin over the chest wall and breast studded with cancer nodules-armour coat Tethering to skin

Ca breast
Spread to deeper planes Pectoralis majorakimbo Latissmus dorsi---extending the arm against res Serratus anterior---pushing wall with extended arms Chest wall---leaning forward,raising the arm Lymphatic spread Sappeys subareolar plexus Cutaneous lymphatics Intramammary lymphatics-all go to Axillary group-75%,,,int.mamm.-25%

Ca breast
Axillary group Anterior or pectoral along lateral thoracic art. Posterior or subscapular Lateral or brachial Central Apical Rotters interpectoral Spreads by permeation,embolization and retrograde manner

Ca breast

Lymphatic manifestations Peau d orange Arm oedema Elephantiasis chirurgens Brawny oedema Lymphangiosarcoma Breast is in subcutaneous plane but its extension,axillary tail of Spence,passes through an opening in the deep fascia-foramen of Langer Independent mobility for node and along with the primary tumour for extension.

Differential Diagnosis of br.ca

Fibroadenosis Traumatic fat necrosis Tuberculosis Bloodgood cyst Filariasis Mastitis Antibioma Galactocoele Mondors disease Phyloides tumour

Breast cancer-diagnosis

1.BSE.over 60% of cases are discovered. 2.physical examinationby physician 3.mammographyreveals architexture.. a.suspicious signs are asymmetry,skin thickening,irregular masses,architectural distorsion and clustered irregular microcalcifications(most important) b.to support the clinical impression of no evidence of malignancy in the follow up and to screen for subclincal tumours. c.current recommendation is a baseline mgm.at the age of 35 then annual screening in high risk

Breast cancer-diagnosis

4.ultrasoundif the breast mass is (palpable or not) solid or cystic 5.needle aspiration for cytology 6.excisional biopsy..a.for HP,b.ER or PR status(+more responsive than ve trs.,c.flow cytometry to determine if the tr.is diploid or aneuploid and to determine the S-phase fraction(aneuploid trs.with a high S-phase fraction have poor prognosis)

Staging-Manchester

Stage One The growth is confined to breast, and is not adherent to pectoral muscles or to chest wall. There are no enlarged nodes in axilla. Adherence to the skin, or ulceration through it, does not affect staging, if it is smaller than the tumour. 68% of all patients survive 5 years, and 54% 10 years. Stage Two As for stage One, but there are now mobile nodes in axilla. 60% of patients survive 5 years and 40% 10 years.

Staging-Manchester

Stage Three There is skin involvement which is larger than the tumour, but it is still limited to breast. If any axillary nodes are palpable, they are still mobile. Or the tumour is fixed to pectoral muscle, but not to chest wall. Or it is fixed to both. 15% of patients survive 5 years and 4% 10 years. Stage Four has distant metastases, either lymphatic, or blood-borne. These include infiltration of the skin beyond breast, fixed nodes in axilla, palpable nodes in supraclavicular fossae, involvement of other breast; or deposits in bones, liver, or lungs (unusual). 4% of patients survive 5 years and 4% 10 years.

TNM STAGING
Breast Cancer T, N, and M Categories Primary tumor (T): TX: Primary tumor cannot be assessed. T0: No evidence of primary tumor. Tis: Carcinoma in situ (DCIS, LCIS, or Paget disease of the nipple with no associated tumor mass) T1: Tumor is 2 cm (3/4 of an inch) or less across. T2: Tumor is more than 2 cm but not more than 5 cm (2 inches) across. T3: Tumor is more than 5 cm across. T4: Tumor of any size growing into the chest wall or skin. This includes inflammatory breast cancer.

Regional lymph nodes (N):

NX: Regional lymph nodes cannot be assessed (e.g., previously removed) N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral axillary lymph node(s) N2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or

to other structures

N3: Metastasis to ipsilateral internal mammary lymph node(s)

Distant metastasis (M):

MX: Presence of distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis present (includes metastasis to ipsilateral supraclavicular lymph nodes)

T0 N0 N1 N2 N3

T1 ONE TWO THREE-A THREE-B

T2

T3

T4

M1

FOUR

TREATMENT PROTOCOL
BIOPSY & WORK UP
STAGE I LUMPECTOMY AX. DISS. RT STAGE II STAGE III STAGE IV

MRM

CT

CT

OR MRM

OR LUMPECTOMY AX. DISS. RT

SURGERY

& / OR RT

Treatment protocol

For stage 2 and stage 3 disease along with the above, adjuvant chemotherapy is used for node-positive cases, and high risk nodenegative pts. Adjuvant hormone therapy is used for those patients with hormone-sensitive tumors.

chemotherapy

Indications Advanced ca. as a palliative procedure After simple mastectomy,in stage 3 with fixed axil.LN In inflammatory ca. In stage 4 with secondaries in bone,lungs,liver Premenopausal age with poorly differentiated trs.

chemotherapy

Toxic effects---alopecia,bone marrow depression,cystitis,nephritis,megaloblastic anemia.. Cyclophosphamide Methorexate 5-fluorouracil CMF In monthly cycles for 6 months.

Hormone therapy -includes

Oestrogen receptor antagonists-tamoxifen Surgical ovarian ablation-bilateral oophorectomy or by radiation LHRH agonists(medical oophorectomy) Oral aromatase inhibitors for post menopausal Adrenalectomy or pituitory ablation Progesterone receptor antagonist Androgens. Aminoglutethimide(medical adrenalectomy) progesterone

Hormone therapy

Tamoxifen It is antioestrogen and blocks the oestrogen receptors.. 10mg.bd of 5 years It is also used in BBD,infertility in males,desmoid tumour

radiotherapy

After conservative breast surgery.breast is irradiated using brachytherapy. After total mastectomy,external irradiation is given to axilla Patients with high risk of local relapse after surgery,a.invasive ca.,extensive insitu ca, under 35 years age,multifocal disease In bone secondaries,to palliate pain and swelling Inflammatory ca.,scirrhous ca,positive surgical margins.. As preoperative radiotherapy,to reduce the tr.size and downstage the tr.so that the operability is good.

Operations for breast ca.

1.total or simple mastectomy tr.+entire breast+nipple areolar complex +skin over the tumour+axillary tail.(no axillary dissection but post op.radiotherapy given to axilla) 2.total mastectomy with axillary clearance TM+removal of axil.fat fascia and lymphnodes 3.MRM-Pateys operation here 2 +removal of pectoralis minor muscle so as to have good access to upper part of axilla and to clear interpectoral (Rotters) nodes.pectoralis major is retained.

Pateys operation

Structures to be retained 1.Axillary vein 2.Bells nerve 3.Cephalic vein 4.Dorsal nerve

N.to ser.anterior

Breast conservative surgery

In stage 1 and2 BCS can be considered which includes Lumpectomy Wide excision QUART.(quadrantectomy+axillary dissection +radiotherapy to the bed of tr.and rest of breast.)