L2 1601 CQ Breast - Oncology Module

8/2/2019 L2 1601 CQ Breast - Oncology Module

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Benign and malignantbreast pathology

Dr. Cecily Quinn

Irish National Breast Screening Programme &St. Vincents University Hospital, Dublin 4


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Breast DiseaseSymptoms

Lump

Smooth, round

Hard, irregular

Lumpy area

Nipple discharge Breast pain

Breast thickening


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Breast DiseaseMammographic abnormality

Density Asymmetry

Mass

Calcification


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Breast DiseaseTriple assessment


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Non-operative breast diagnosisPathology

Breast:needle core biopsy B1 normal tissue or non-diagnostic

B2 benign

B3 - heterogenous group of lesions

Risk concomitant malignancy e.g. radial scar

More significant pathology in vicinity

B4 suspicious

B5 malignant in situ or invasive


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Anatomy of the breast


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Benign Breast DiseaseSpectrum of lesions

1. Cysts, duct ectasia,

2. Fibroadenoma

3. Potential for local recurrencePhyllodes tumour

4. Increased incidence of associated malignancy

Radial scar, papilloma5. Atypical lesions

Atypical ductal hyperplasia, lobular neoplasia


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Cyst(s)

Pathology Fluid filled dilated

breast gland (acinus)often lined byapocrine epithelium

Solitary

Multiple +/- otherbenign change =fibrocystic disease


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Cyst(s)

Clinical Asymptomatic Mammographic lesion Smooth lump Lumpy area Cyclical pain & nodularity

Management

No treatment Aspiration May be excised if part of

a more complex lesion


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Duct ectasia

Pathology Affects breast ducts

Duct dilatation,

Accumulation of secretions

Periductal inflammation &fibrosis

Periareolar abscess

Cause Smoking

Hyperprolactinaemia

Bacteria


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Duct ectasia

Clinical Nipple discharge

Lump Pain Calcification

Management Subareolar

exploration


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Fibroadenoma


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Phyllodes tumour


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Phyllodes tumour

Potential for localrecurrence

Clinical Mammographic lesion

Lump

Size: 1cm 45cms

Management Complete excision

with 1cm rim ofnormal tissue note 1


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Radial Scar

Pathology Spiculate lesion

Benign tubules in sclerotic

stroma Associated benign changes

May mimic carcinoma,mammographically and

pathologically Associated malignancy in up

to 33%


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Radial scar

Clinical Mammographic lesion

Lump

rare

Management Complete excision to

exclude malignancy


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Papilloma

Pathology Intraductal lesion

Solitary or multiple

Heterogeneous Only part represented in

needle core biopsy


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Papilloma

Clinical Women in 5th and 6th

decades

Asymptomatic Mammographic lesion Nipple discharge Lump

Management Excise in view of

heterogeneity


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Atypical ductal hyperplasia

Pathology Proliferation of epithelium lining the ducts and acini

Some but not all of the features of DCIS


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Atypical ductal hyperplasia

Diagnosis Needle core biopsy for evaluation of

mammographic or symptomatic lesion

Management Excise in entirety to evaluate adjacent tissue

for ductal carcinoma in situ

Risk for malignancy Increased (normal x 4)

Mammographic surveillance


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Lobular neoplasia

Atypical lobular hyperplasia

Risk x 4 normal

Lobular carcinoma in situ

Risk x 11 normal


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Lobular neoplasia

Clinical Incidental finding No clinical or mammographic equivalent

Traditional teaching Risk factor for breast cancer Risk applies equally to both breasts No point in trying to excise Treatment options

Mammographic surveillance Bilateral mastectomy


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Lobular neoplasia

Recent studies (Molecular analysisand longitudinal patient studies):

Subgroup may act as a precursor lesion (likeDCIS) and progress to invasive carcinoma

Treatment approach likely to change inthe future


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Breast Cancer in Ireland

Affects 1 in 12women

1800 women newlydiagnosed each year

600 women die fromthe disease each

year 12,000 person years

of life lost each year

due to breast cancer


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Breast Cancer

We do not know what actually causesthis common disease

We have identified risk factors


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Breast Cancer Risk

Family history (20%) Specific genetic abnormality

BRCA1 gene

85% risk Reproductive profile

Uninterrupted oestrogenic stimulation

Exogenous hormones OCP, HRT


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Breast Cancer Risk

Lifestyle Alcohol, diet, smoking

Environmental Radiation

Sociodemographic Residence in developed countries


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Breast Cancer Risk

Breast biology Atypical ductal hyperplasia

Lobular carcinoma in situ

Ductal carcinoma in situ

Cancer in contralateral breast


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Breast CancerDiagnosis

Non operative 95%Triple assessment Clinical assessment

Radiology Pathology

Needle core biopsy

Fine needle aspirate

Multidisciplinary review

Operative 5%Open surgical biopsy


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Non-operative breast diagnosis

Pathology

Breast:needle core biopsy B1 normal tissue or non-diagnostic

B2 benign

B3 - heterogenous group of lesions Risk concomitant malignancy e.g. radial scar

More significant pathology in vicinity

B4 suspicious

B5 malignant in situ or invasive

Axillary lymph nodes:fine needle aspirate

Negative

Positive


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Non-operative breast diagnosisGuide to surgery

Wide local excision or mastectomy? Size or extent of lesion

Sentinel node biopsy or axillary clearance? SNLB invasive carcinoma, high grade DCIS

AXCL

known positive lymph node


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Non-operative breast diagnosisGuide to non-surgical treatment

Neoadjuvant (Chemo before surgery

) chemotherapy Extent of disease clinical & radiology

Pathology to confirm diagnosis

Hormone treatment only Exceptional

ER and PR receptor status


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Pathological evaluation of therapeutic

operative breast cancer specimens

he will manage thecure best who hasforeseen what is tohappen from thecurrent state ofmatters

Book of Prognostics

Hippocrates 400BC


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Breast CancerClassification

In situ carcinoma

Ductal DCIS

Lobular LCIS Invasive carcinoma

Ductal

Lobular

Special types


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Obligate precursor lesion

Recur if left untreated

50% as invasive carcinoma

20% screen detected cancers

Malignant cells contained within

the glandular system of breast

Complete removal should cure


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Old classification

Architectural patterns

Comedo

Solid

Cribriform

Micropapillary

Not reproducible

Not clinically relevant


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New classification

Nuclear grade

High

Intermediate

Low

Reproducible

Clinically relevant

Ductal carcinoma in situNuclear grade


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Ductal carcinoma in situSize of lesion

< 15mm

15 40mm

> 40mm


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> 10mm

1 10mm

< 1mm

Ductal carcinoma in situMargin status


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Ductal carcinoma in situVan Nuys Index

Nuclear grade 1 - 3

Margin status 1 - 3

Lesion size 1 - 3

Silverstein at al, Lancet 1995

35 WLE only 5, 6 WLE & RoRx

8, 9 Mastectomy


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Invasive breast carcinomaPrognostic parameters

Type

Grade

Size Margin status

Lymphovascular invasion

Lymph node status

Hormone receptor status

Her-2/neu status


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Invasive ductal carcinoma


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Invasive lobular carcinoma

Tends to infiltrate thebreast insidiously

Forms irregular lesion Mammogram may be

negative

Increased multifocality

Increased bilaterality E-cadherin negative

MRI scanE cadherin

I i b i


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Mucinous BasalTubular

Invasive breast carcinomaSpecial types

I i b i


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Invasive breast carcinomaTumour size

Powerful indicator of patient survival

WLE vs mastectomy

Tumour > 2cm chemotherapy

Removal of tumour


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THE IRISH TIMESWednesday, September 1, 2004

North reaps benefit of

breast cancer screeningDeaths from breast cancer

falling by 4% per annumMuiris Houston, Medical Correspondent

Tumour size is a surrogate marker for monitoring efficacy of screeningprogrammes until improved mortality becomes apparent

I i b t i


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Invasive breast carcinomaTumour grade

G2 G3G1

Invasive breast carcinoma


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Invasive breast carcinomaAdequacy of excision

Positive or close

margins predict localrecurrence further surgery



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Invasive breast carcinomaLymphovascular invasion

Independent predictorof survival

Correlates with lymphnode involvement

Surrogate marker oflymph node status

? Chemotherapy

I i b t i


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Greatest predictor ofpatient survival

Component of TNMstaging system

Major factor in patientselection for

chemotherapy

Invasive breast carcinomaLymph node status


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Sentinel lymph node biopsy

The lymph node thatis most likely toharbour metastases

if patient is LNpositive

Reliable alternativeto axillary lymphnode clearance as astaging procedure


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Sentinel lymph node biopsy

Removal of oneversus 30 LNs

allows for enhancedpathological analysis

Greater chance ofdetectingmetastases


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Axillary lymph node clearance

Positive lymph node fine needle aspirate

One operation

Positive sentinel lymph node Two operations

Number of positive lymph nodes per total

lymph node count

I i b t i


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Invasive breast carcinomaNottingham prognostic index

Tumour size (cms) x 0.2

+

Grade (1, 2, 3)

+Lymph node status (1, 2, 3)

Three prognostic groups

In si e bre st c rcinom


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Invasive breast carcinomaEffect of NPI on survival

0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5

0

10

20

30

40

50

60

70

80

90

100

110NPI 3.4

NPI 3.4-5.4

NPI 5.4

Years

P

ercentage

su

rvival

Chemotherapy



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Invasive breast carcinomaPredictive parameters

Oestrogen receptor

Immunohistochemistry

Fluorescence In Situ Hybridisation

HER2

Immunohistochemistry

Molecular classification


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Molecular classificationInvasive breast carcinoma

Luminal A Strong ER/PR positiveLow proliferation rateHer2 negative

Luminal B Weak ER / PR positiveHigh proliferation rate

May be Her2 positive

HER2 ER & PR negativeHer2 positive

Triple negative ER, PR & HER2 negative


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Gene expression signature predicts


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295 patients with primary breast cancer

Stage I or II

< 53 years Lymph node status:

negative = 151; positive = 144

70 gene prognosis profile

Van de Vijveret al NEJM 2002


survival in breast cancer



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Two groups

Good prognosis 115 patients (97% ER

positive) Poor prognosis 180 patients

More powerful predictor of outcomethan conventional histological criteria


survival in breast cancer


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Oncotype Dx test

Multigene expression test Genomic Health

Stage 1 or 2 disease

Hormone receptor positive [ER or PR]

Lymph node negative

Predicts response to chemotherapy and

likelihood of tumour recurrence


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Oncotype Dx test


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TNM classification Tumour

T0: No evidence of primary tumor

Tis: Carcinoma in situ

T1: Tumor 2.0 cm or less in greatest dimension

T2: Tumor more than 2.0 cm but not more than 5.0 cm in greatestdimension

T3: Tumor more than 5.0 cm in greatest dimension

T4: Tumor of any size with direct extension to (a) chest wall or (b) skin,


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TNM classification Lymph Nodes

NX: Regional lymph nodes cannot be assessed

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 eachother or to other structures

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


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TNM classification Metastases

MX: Presence of distant metastasis cannot be assessed

M0: No distant metastasis

M1: Distant metastasis present (includes metastasis toipsilateral supraclavicular lymph nodes)


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Tumour stage AJCC

Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage IIA T0 N1 M0: T1 N1 M0: T2 N0 M0 Stage IIB T2 N1 M0: T3 N0 M0 Stage IIIA T0 N2 M0: T1 N2 M0: T2 N2 M0: T3 N1 M0: T3 N2 M0

Stage IIIB T4 Any N M0: Any T N3 M0 Stage IV Any T Any N M1

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L2 1601 CQ Breast - Oncology Module