breast carcinoma,pathology (dr ladipo)

8/3/2019 Breast Carcinoma,Pathology (Dr Ladipo)

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Presented by

DR LADIPO T.A

DEPARTMENT OF RADIOTHERAPY

NHA


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Breast cancer is one of the major diseases ofpublic health importance.

Worldwide it is the most common cancerin women. It affects about 1% of male

population. Breast cancer is second only to lung cancer in

mortality world wide.Incidence varies greatly around the world,

being lower in less-developed countriesand greatest in the more-developedcountries.


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A TIP OF THE ICEBERG


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Breast cancer is the leading cause of death inwomen aged 45-50yrs.

The 5yr survival is 60% overall but is greaterthan 80% for early disease.(Hemant singal etal,2009)


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It is rarely found before the age of 25yrsexcept in certain familial cases.

Rates are high in USA,Scotland and westernEurope.

Estimated new cases and deaths from breastcancer in the United States in 2008:New cases: 182,460 (female); 1,990 (male)

Deaths: 40,480 (female); 450 (male)(Breast cancer.org.)

At U.C.H diagnosed in 22yr old female.


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Women in the US have 1 in 8 (12.5%) lifetimechance of developing invasive breast cancerand 1 in 35 (3%) chance of breast cancercausing their death.

Breast cancer affects African-Americanwomen less than white women.

Black women are less likely to get the

disease, but are more likely to die from it.Black women also get the disease at youngerage than white women.


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The rate of breast cancer is very low in Japan,India and some areas of Africa .

Its the most common cancer in Nigeriaaccounting for 29.7% of 818 cancercases(Ibadan cancer registry).

The peak age incidence in Nigerian women isabout a decade earlier than in Caucasians.

It was estimated that between 7-10 thousandnew cases of breast cancer developed inNigeria in 2005.(Adebamowo et al).


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Somatic mutations theory postulates theaccumulation of mutations in somatic genesthat progressively deregulate normal breastbehavior,

The cell is believed to be the epithelial celllining the terminal duct lobular unit,

Several processes predispose to mutation

including exposure to mutagens e.g.radiation, mitogens such as estrogen,


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Mitogens are thought to predispose tomalignant transformation by increasing therisk of unrepaired DNA replication errorsduring stimulated cell division.

Over expression of certain genes e.g.epidermal growth factor, HER-2, is associatedwith high nuclear grade,(25% of all B.C)

Others are p53(the guardian of the genome),cowden syndrome(PTEN),Ataxiatelegiectasia(ATM)


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Inheritance of high penetrance dominantmutations account for 5-10% of breast ca andtypically presents with a strong family historye.g. BRCA1&2 genes.

The biochemical basis of the cellular effect isa repair defect, rendering the genome proneto mutation a state referred to as genomicinstability.(Treatment of cancer 4th edition-Pat Price&Karol Sikora).


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MAJORo Female gender(M:F 1:100)o Increase age(late 30s-0.07% risk,70s-0.44%)

o western culture(dietary and enviromental)

o Family history( 1.7% and 1.4% in 1st & 2nddegree relatives respectively)

o Benign breast dx (proliferative benign dxs)

o Radiation( children & adolescent)

o Prior diagnosis of breast ca(10-15% incontralateral dx risk)

o Mutation in BRCA 1% 2( 64% & 45% respectively)


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MODERATEo Early menarche/ late menopause

o Nulliparity / delayed full term preg.

o

High socioeconomic statuso Country of residence

o Alcohol intake

o Obesity

o Prior diagnosis of uterine, ovarian, or colonicca.


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OTHERS;o Oral contraceptive pills

o Hormone replacement therapy

o

High density breast mammograpyo High fat diet,

o Drugs-antihypertensive(Rauwolfia cpds)

(Cancer medicine 4th edition-Holland et al).


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Some risk factors associated with bilateraldisease are;

o Young age at first onset.

o Positive family history.

o Multicentric disease in ipsilateral breast.

o Invasive lobular subtype


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Considering the combination of risk factors in anindividual ,it is possible to predict his annual andlife time risk of breast ca.

Gail et al uses these epidemiological factors to

derive a model for predicting breast ca risk. Commonly used by Gail are;

o Age at presentation

o Nos of 1st degree relativeso Age at 1st birth

o Age at menarche

o No of biopsy & result


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Based on the model people with high risk ofdeveloping breast ca.are councel to considereither prophylactic tamoxifen use orprophylactic surgery.


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TAMOXIFEN ;o Reduce the incidence of invasive & non

invasive by 49% & 50% respectively(Perez etal)

o Decreases the incidence of contralateralbreast ca(NSABP)

o Individuals with high risk detected using Gail

model who uses tamoxifen for 5yrs, haveincrease 5yrs free dx rate(Perez et al)


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PROPHYLACTIC SURGERY; Results shows 89.5% decrease in risk for

those that had this procedure(Mayo clinic1993)


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Lower age at first childbirth (less than 24 yearsmaternal age),

Multiparity (about 7% lowered risk per child),

Breastfeeding (4% per breastfeeding year, with

an average relative risk around 0.7%) Breast ca risk decreased by 7% for every

12months of breastfeeding

Adebamowo CA , Campbell O B , Adenipekun A ,et al ( Br J Cancer 2008)

In addition, exercising three times a week for onehour each has been found to lower breast cancerby up to 40%


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The (2003) World Health Organization (WHO)classification of tumors of the breastrecommends the following pathological typesInvasive breast carcinomas

Invasive ductal carcinoma Most are "not otherwise specified" The remainder are given subtypes:

Mixed type carcinoma

Pleomorphic carcinoma

Carcinoma with osteoclastic giant cells

Carcinoma with choriocarcinomatous features

Carcinoma with melanotic features


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Invasive lobular carcinoma Tubular carcinoma

Invasive cribriform carcinoma

Medullary carcinoma Mucinous carcinoma and other tumors with

abundant mucin Mucinous carcinoma

Cystadenocarcinoma and columnar cell mucinouscarcinoma

Signet ring cell carcinoma


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Neuroendocrine tumors Solid neuroendocrine carcinoma (carcinoid of the

breast)

Atypical carcinoid tumor

Small cell / oat cell carcinoma Large cell neuroendocrine carcioma

Invasive papillary carcinoma

Invasive micropapillary carcinoma

Apocrine carcinoma


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Metaplastic carcinomas Pure epithelial metaplastic carcinomas

Squamous cell carcinoma

Adenocarcinoma with spindle cell metaplasia

Adenosquamous carcinoma Mucoepidermoid carcinoma

Mixed epithelial/mesenchymal metaplasticcarcinomas


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Lipid-rich carcinoma Secretory carcinoma

Oncocytic carcinoma

Adenoid cystic carcinoma Acinic cell carcinoma

Glycogen-rich clear cell carcinoma

Sebaceous carcinoma

Inflammatory carcinoma


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Sarcomas:-Angiosarcoma

-Liposarcoma

-Rhabdomyosarcoma-Leiomyosarcoma

-Fibrosarcoma


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Precursor lesions Lobular neoplasia

lobular carcinoma in situ(LCIS)

Intraductal proliferative lesions Usual ductal hyperplasia

Flat epithelial hyperplasia

Atypical ductal hyperplasia

Ductal carcinoma in situ(DCIS)

Microinvasive carcinoma


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Intraductal papillary neoplasms Intraductal papillary carcinoma

Intracystic papillary carcinoma


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Tumors of the nipple Paget's disease of the nipple

Malignant lymphoma Metastatic tumors Tumors of the male breast Carcinoma

In situ

Invasive


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Multiple tumor grading systems have beenproposed. The Scarff-Bloom-Richardsonclassification system utilizes mitotic index,differentiation, and pleomorphism, each with

scores of 1 to 3. Scores of 3 to 5 are welldifferentiated, 6 to 7 moderatelydifferentiated, and 8 to 9 poorlydifferentiated. This system is commonlyemployed and has been shown to be ofindependent prognostic significance

Nottingham model.


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Actual field size 150 X 100 microns) Arrow heads show themyoepithelial cells apposed to the basal lamina. Ductal cells(short arrows) are partly overlapping in this section but form asingle cell layer above the myoepithelium. Long thin arrows showseveral of the periductal fibroblasts. These have characteristiclong pointed nuclei, they show a typical orientation of their long

axis parallel with the basal lamina, and they appear inactive(heterochromatic nuclei) in this duct. Mature collagen with a wavy


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Figure 28: DCIS with invasive ductal carcinoma, high magnification. (Actual field size 360 X 240 microns) This is from the same patient as Figure 27, but from a

different area of the biopsy. The arrow heads outline a focus of intraductal carcinoma. This DCIS hasa smooth outer contour, and the extracellular matrix has a normal concentric arrangement aroundthis duct. The fibroblasts around this duct (thin arrows) are thin, arranged in the normal parallelorientation to the duct, and they appear inactive since they do not have much euchromatin ornucleoli. In contrast, the other ductal cells are all "invasive" and show a ragged contour without anorganized concentric wrap of extracelluar matrix around them. The fibroblasts near the invasiveductal cells appear highly active (thick arrows) with open chromatin and nucleoli. The products ofthe active fibroblasts include bubbly bluish mucopolysaccharides and young finely fibrillar collagen.To diagnose invasion, it is often essential to look at the non-neoplastic stromal cells.


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(T) -Primary TumorTx - Primary tumor cannot be assessed.

T0 - No evidence of primary tumor.

Tis - Carcinoma in situ.Tis(DCIS) - Intraductal Carcinoma in situ.

Tis(LCIS) - Lobular Carcinoma in situ.

Tis(Paget's) - Paget's disease of the nipple with

no tumor.


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T1 - Tumor 2cm or less in its greatestdimension. T1mic - Microinvasion 0.1cm or less in greatest

dimension. T1a - Tumor more then 0.1cm but not more than

0.5cm in its greatest dimension. T1b - Tumor more than 0.5cm but not more than

1.0cm in its greatest dimension. T1c - Tumor more than 1.0cm but not more than

2.0cm in its greatest dimension. T2 - Tumor more than 2.0cm but not more

than 5.0cm in its greatest dimension.


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T3 - Tumor more than 5cm in its greatestdimension.

T4 - Tumor of any size with direct extensionto (a) chest wall or (b) skin as described

below: T4a - Extension to chest wall.

T4b - Oedema (including peau d'orange) orulceration of the breast skin, or satellite skin

nodules confined to the same breast. T4c - Both T4a and T4b.

T4d - Inflammatory breast cancer.


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Lymph NodeThere are four lymph node classification

values (N0, N1, N2 or N3) which depend onthe number, size and location of breast

cancer cell deposits in lymph nodes.

o Nx - regional lymph nodes cannot beassessed. Perhaps due to previous removal.

o

N0 - no regional lymph node metastasis.


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o N1 - metastasis to movable regional axillarylymph nodes on the same side as the affectedbreast.

o N2 - metastasis to fixed regional axillary lymph

nodes, or metastasis to the internal mammarylymph nodes, on the same side as the affectedbreast.

o N3 - metastasis to supraclavicular lymph nodes

or infraclavicular lymph nodes or metastasis tothe internal mammary lymph nodes withmetastasis to the axillary lymph nodes


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MetastasesThere are two metastatic classification

values (M0 or M1) which depend on thepresence or absence of breast cancer cells in

locations other than the breast and lymphnodes (so-called distant metastases, e.g. tobone, brain, lung).

o M0 no distant metastasis

o M1 distance metastasis is present


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STAGE-1 Tumor confined to breast and notattached to underlying muscle.

no axillary LN.

STAGE-2 As in stage 1,but axillary LN are

involved but mobile. STAGE-3 I-Skin involvement beyond periphery

of tumor or

ll-tumor attached to underlying

muscle lll-Axillary LN are mobile or fixed.

There are no distant metastasis.


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STAGE 4 l-Lymphatic spread is beyond theipsilateral axilla.

ll-Distant blood-bornemetastasis


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STAGE 5yr survival(%) 10yr survival(%)0 99 95

1 97 88

II 83 66

III 54 36

IV 16 7


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PAINLESS BREAST LUMP. .BLOOD STAINED NIPPLE DISCHARGE(DUCT

CA)

RETRACTION OF THE NIPPLE

LYMPHEDEMA OF THE BREAST&/ARM.

ECZEMA OR DERMATITIS OF THEAREOLA(PAGETS DX)


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METASTASES;o Pulmonary- Cough, dyspnea.

o Bone deposit- bone pain, pathologic #, bonyswellings of skull, ribs, clavicle.

o Cord compression from vertebra deposits or# may result in paraplegia.

o Liver -hepatomegaly,ascites.

o Brain metastasis-features of raised ICP.


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FIBROADENOMA CYST

GALATOCELE

CHRONIC BREAST ABSCESS

TRAUMATIC FAT NECROSIS


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LOCAL INVASION LYMPHATIC SYSTEM

BLOOD STREAM


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Most common site-upper outer quadrant. Commoner on the left breast

Unusual for both to occur simultaneously

The growth travels along the duct

Breaks through the basement mmb. of ductinvading adjacent duct, fascia, mammary fat,spreading through breast lymphatics to

peripheral lymphatics.


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Common route, first to the axillarynodes(increases with tumor size)

Then to other nodes-internal mammary,supraclavicular LN,

Then vascular invasion by tumor &haematogenous metastasis.

(Carlos Perez & Co prin. & prac. of Radiology

oncology 3

rd

ed)


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BREAST SELF EXAMINATION CLINICAL BREAST EXAMINATION

MAMMOGRAPHY


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Starting at 40yrs,yearly mammograpy shouldbe done.

Clinical examination by a physician every 3yrsfor those in 20s and 30s and annually for

those with 40yrs and above. Breast self examination monthly starting with

women in there 20s.

Those with high risk(family history,|)shouldhave earlier mammograpy starting at25yrs.US &MRI can also be done.


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HISTORY-menstrual status, parity, family hx , PHYSICAL exam- breast, axillary LN (size,

mobility, no), supraclavicular fossa,abdomen, spine.

Excisional biopsy if lump is small

Otherwise incisional biopsy

Core needle biopsy

Histological diagnosis ER/PR and HER2/neu


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RADIOLOGIC studies-mammography,ultrasound, CXR, abdominopelvic USS, Bonescan, MRI, CT scan.

LAB studies- FBC, E/U & Cr, alkaline

phosphatase, LFT. Urinalysis.

Tumour markers.

Oncogene assay- BRCA 1 & 2, HER-2


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INTRINSIC:o Axillary nodes(1-3 ,73% 5yr survival rate)o Tumor size(


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o Presence of multiple primary tumor(multicentricity).

o Proliferative rate (High)- mitotic index,thymidine labeling index, s-phase fraction-

poor prognosis.o Over expression of her-2, CA-15-3, CA27-

29, Epidermal growth factor

o Lymphovascular invasion(recurrence rate for

LVI+VE -38%,LVI-VE -22%)o P53-over expression-poor prognosiso Tumor location medial tumors worst prog.


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EXTRINSIC Factors:o Age-worse with younger age(ER-ve

status,high grade dx)

o Race-Black women,advanced stages.

o Obesity-Greater risk of reoccurrence.

o Smoking??


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Rare occurrence. Incidence


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Same histologic subtypes of invasive cancer. More rapidly infiltrates to become attached to

overlying skin and thoracic wall.

Distant metastasis to lungs,brain,bone&liver

are common.

Presents in a more advanced stage in men.

Estrogen receptor tumor is more predominant

in males.


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Among women with breast ca 1-2% arepregnant. No evidence that pregnancy is associated with

either the development or progression of

breast ca. Prognosis is related to stage,worse prognosis

because;

-Delayed diagnosis

-Reluctance with use of mammograpy -Changes in the breast during pregnancy

makes cancer difficult to detect.


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This is a type of breast cancer that is clinicallynegative for ER/PR and HER-2 proteins. Constitute of 15% of all breast cancer in

USA(medscape 2009) Its more common in;o Carriers of BRCA-1 gene mutationo Young womeno African-American women HIGHEST RISK young and african-American It is characterized by its unique molecular profile,

aggressive behavior, distinct patterns ofmetastasis, and lack of targeted therapies.


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UP to 50% of breast cancer patient in Africahave this disease.Although;

o Data collection?

o Screening tools?

(Lisa carey et al,medscape 2009)

TNBC is a traumatic diagnosis to both theclinician and patient as it doesnt respond to

conventional treatment.


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As opposed to other breast cancer types,itsresponse to chemotherapy is better withPlatinum compound(Effective for BRCA-1disease) than with anthracyclines and taxanes

Screening for early detection is a problem dueto poor access to the facilities especially inAfrica due to poverty

Also some with high risk are too young forstandard screening


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More researches are on the way to unveilpromising treatment modalites;o Antiangiogenic agents e.g intergroup

E5103(early disease)

o PARP (ADP-ribose polymerase) inhibitorso EGFR, C-KIT inhibitorso MAP-kinase inhibitorso Mtor inhibitors

o -VEGFo HER/1


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THANK YOU

breast carcinoma,pathology (dr ladipo)

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