BREAST CANCER

Dr. Susan J. RobertsonDr. Carolyn NessimNovember 17, 2015

The richness of the human experience would lose something if

there was nothing to overcome.

Helen Keller

Objectives• Describe the approach and management of breast cancer• Discuss the biopsychosocial impact of breast cancer• Describe the pathogenesis of breast cancer• List hormonal receptors in breast cancer and their significance• List common metx for breast cancer• Breast cancer TNM staging• Recognize proliferative breast disease as a risk factor for breast cancer• Recognize the pathogenesis in breast cancer includes some specific familial factors• DCIS, LCIS, invasive• Prognosis of breast cancer• Microscopic features of breast cancer in risk analysis and therapeutic options• Important prognostic factors for breast cancer• ER and PR and Her2 neu status• Differentiate between benign and malignant breast conditions based on clinical

presentation, imaging and pathology• List risk factors for the development of breast cancer• Explain the concept of BIRADS and its importance for risk assesment of breast cancer• Given specific clinical presentations, select appropriate investigations and treatment

options

Disclosure

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Statistics

• In 2015,– An estimated 25,000 Canadian women will be diagnosed

with breast cancer and 5,000 will die from it– Approx. 67 Canadian women will be diagnosed with

breast cancer every day and 14 will die of the disease every day

– 1 in 9 women will develop breast cancer during her lifetime, and 1 in 29 will die from it

– It is expected that 210 men will be diagnosed with breast cancer and 60 will die from it

– 5 year survival for men is 80% and 88% for women– Hereditary cancers account for only 5-10%

Incidence

NORMAL

ATYPICAL DUCTAL HYPERPLASIA (ADH)

DUCTAL CARCINOMA IN SITU (DCIS )

INVASIVE DUCTAL CANCER

LYMPHATICSBLOOD VESSELS

LYMPH NODES

MILK DUCT

HOW DUCTAL CARCINOMA DEVELOPS….

Classification of Primary Breast Cancer

• PRE-INVASIVE CANCERS– These lesions do not cross the basement membrane and therefore

CANNOT spread– ANAOLOGY: Colorectal polyp– LCIS (Lobular Carcinoma In Situ)

• Classical• Pleomorphic

– DCIS (Ductal Carcinoma In Situ)• Papillary• Cribiform*• Solid*• Comedo• Micro-papillary

DCIS

• DCIS is a pre-cancer• If left untouched, 30% will develop into cancer• We cannot identify which will transform• All treated the same• This may change as molecular and genetic

analysis improves

LCIS

• Is a marker of risk• Relative risk of developing cancer is 8-10x the

average population• Lifetime risk of at least 30%• Can develop either a ductal or lobular breast

cancer in either breast

Pathology

Ductal Carcinoma in Situ

• Can present as a mass, but rare, often non-palpable

• Can present radiologically • Can include calcifications• In common all subtypes = Non invasive• Microscopically can be different patterns and

can be high or low nuclear grade

DCIS - low nuclear grade

• Lower grades of DCIS less likely to be associated with zonal necrosis or abundant calcium

• This pattern is called cribriform

• The calcium here is fine and related to extracellular secretions

From Robbins

Calcium

Ductal Carcinoma in Situ Higher nuclear grade DCIS with

zonal (comedo)necrosis and superimposed calciumLinear and branching calcifications

Lobular carcinoma in Situ (LCIS)• Classic LCIS is non invasive cells that look like invasive lobular

carcinoma involving lobules or ducts.• smaller less pleomorphic nuclei some dyscohesive properties

and some special staining properties. • LCIS acts more as a marker of increased risk rather than an

actual precursor lesion because LCIS did not predict laterality of invasive cancer.

• The relative risk of subsequent invasive cancer in patients with LCIS about 8.0X in the first 15 years following a biopsy of LCIS.

• The majority of lesions are invasive ductal (49%), but invasive lobular occurs at a higher frequency (23%) than in the general population

Management of DCIS• Management of the Breast• Localized

– Lumpectomy + Radiation• Widespread

– Mastectomy with or without Reconstruction– No radiation

• Management of the Axilla– NO Sentinel node biopsy unless….

• Mastectomy – due to 20% upgrade risk to cancer• UOQ lesion – technical reason

Management of DCIS• Margin status is 3 times as powerful as tumour grade in determining the

risk of recurrence

• Often cannot see or feel the lesion – needing wire guidance

• Has been quoted that need 1cm margins (highly unrealistic with poor cosmetic result defeating the purpose of BCS)

• Studies have shown that a 1-2mm margin for DCIS is as good as 1cm with no evidence of increased local recurrence

• If margin is positive or close (≤ 1mm) – must re-excise prior to radiation

Kopans wires in place

Specimen radiograph

Margin Marking Always mark and image the specimen to ensure you took out the right thing!

One thing for sure, if doing lumpectomy – Need radiation

TRIAL # Pts Mean F/u mths

Type of Recurrence

% recurrence Ex only

% Recurrence Ex+EXRT

P value

NSABP B-06 48 83 IBTR 43 7 P<0.0001

IBTR Invasive

23 3.5 p<0.0001

NSABP B-17 813 144 IBTR 31 15 P<0.00005

IBTR Invasive

16 7 P<0.0001

EORTC 10853

1010 51 IBTR 16 9 P=0.005

IBTR Invasive

8 4 P=0.04

Three prospective randomised trials with lack of data on (*margins, tumor size, tissue processing, mammographic- pathologic correlation)

2/3 risk reduction

Lumpectomy vs. Mastectomy

• How to choose?– Contra-Indications to BCS

• Multicentric – Multifocal disease• Disease to Breast size ratio is unreasonable for good

cosmetic outcome• Radiation is contra-indicated (previous

radiotherapy, pregnancy, active vasculitis)• One to Two re-excisions margins remain positive on

pathology• Patient preference

Management of LCIS

• When LCIS on biopsy from an imaging abnormality – Must excise because LCIS does not give an imaging

abnormality– Risk 15% of underlying DCIS or Invasive cancer– Excisional biopsy – No need for re-excision if classic LCIS and positive

margins

Management of LCIS

• Pleomorphic LCIS– Same as DCIS

Paget’s Disease

• Clinical presentation– Exzema of the nipple– Bloody discharge– Itchiness of the nipple– Often associated with underlying DCIS and

sometimes invasive cancer

Paget’s disease

• Management– Attempt steroid cream– NEEDS follow up, if doesn’t improve requires

punch biopsy– Mammogram and US– If Mammogram negative – MRI to ensure no

associated lesion (DCIS or invasive)– If associated lesion, treat as an invasive cancer or

DCIS

Pagets Disease - a complication of DCIS or invasive cancer

• Crusted eczema like change of breast skin of nipple caused by breast carcinoma

• Centered in nipple can extend to areola and surrounding skin but rarely very far

• If with a mass is usually with invasive component but if not palpable 2/3 are just with DCIS

Paget’s Disease Move

Mayo.com

Malignant cells invading epidermis

Invasive Cancer

• Most common = Invasive ductal carcinoma– More often unifocal, unilateral– 80% ER+, 15% Her-2, 15% triple negative– Mets to lung, liver, bone

• Next most common = Invasive lobular– Most often ER+– Large at diagnosis– Difficult to see on Mammogram – Indication for MRI– Tendency to be bilateral and multicentric– Mets to serosal surfaces and meninges

Risk Factors for Breast Cancer• Age – risk increases as you get older• Personal history of breast cancer• Mutations: BRCA1, BRCA2, p53, Cowden etc.• First degree relative with breast cancer• Early menarche (before age 12)• Late menopause (after age 55)• Taking hormone replacement therapy• Nulliparity or first live birth after age 30• Being overweight after menopause

Other risk factors

• These factors have less consistenly shown to increase risk:– Alcohol, more than one glass per day– Breastfeeding – the longer you breastfeed, the

more protective the effect– Being physically inactive- we should be exercising

30 minutes per day– Smoking associated with higher rates of breast

cancer and other cancers

T,N,M Classification• Tumour

– Tis Carcinoma in situ– T1 Tumour < 2 cm– T2 Tumour > 2- <5 cm– T3 Tumour > 5 cm– T4 Tumour any size with extension to the chest wall or skin (includes

inflammatory breast cancer)• Nodes

– N0– N1 1 to 3 lymph nodes positive– N2 metastasis to 4-9 lymph nodes, or positive internal mammary

clinically with negative axilla– N3 Metastasis to > 10 lymph nodes, or combination of

int.mammary and axillary (+ or - supraclavicular lymph nodes)• Metastasis

– M0 no mets, M1 distant metastasis

Breast Cancer StagingSTAGE TNM 5 YEAR RELATIVE SURVIVAL RATE (%)

0 Tis, N0, M0 100

I T1, N0, M0 100

IIA T0, N1, M0T1, N1, M0T2, N0, M0

92

II B T2, N1, M0T3, N0, M0

81

IIIA T0, N2, M0T1 or T2, N2, M0T3, N1 or N2, M0

67

IIIB T4, N0 or N1 or N2, M0 54

IV Any T, Any N, M1 20

Survival by Nodal Status & Tumour Size

Invasive Carcinoma• Clinical Presentation is as a painless mass or

via screening. • Irregular rather than round, hard• if more advanced non mobile or causing

distortion or skin changes including dimpling or peau d’orange, nipple inversion.

• Can be associated with palpable axillary nodes• Rare case inflammatory carcinoma swollen

red thickened skin, rapidly progressing

Breast Exam

Nipple Inversion

Peau d’orange

Inflammatory Breast Cancer

Imaging

• Mammogram• Compression views• US and biopsy (as already discussed)• BiRADS as already discussed

Indications for Breast MRI• Screening:

– BRCA carriers– Lifetime risk ≥25% (Gail Model, IBIS, BRCAPRO)– Previous treatment for Hodgkins Lymphoma

• Diagnostic:– Invasive Lobular Carcinoma– BRCA Carriers– Neo-adjuvant chemotherapy– Paget’s disease of the Nipple– Unknown primary

Cancer Continuum

Classification of Primary Breast Cancer

• Invasive Epithelial Cancers– Invasive lobular carcinoma (10-15%)– Invasive ductal carcinoma (85-90%)

• NOS (not otherwise specified) 50-70%• Tubular carcinoma (2-3%)• Mucinous or colloid carcinoma (2-3%)• Medullary carcinoma (5%)• Invasive cribiform carcinoma (1-3%)• Invasive papillary carcinoma (1-2%)• Adenoid Cystic carcinoma (1%)• Metaplastic carcinoma (1%)

Classification of Primary Breast Cancer

• Mixed Connective and Epithelial Tumours

– Phyllodes tumours, benign and malignant– Carcinosarcoma– Angiosarcoma

• Can be de novo• Usually in the dermis after radiation to chest wall , or in the

lymphedematous tissue in the upper extremity after mastectomy (median time to recurrence after mastectomy is 8 months and the median survival time is 2 years)

Management of Early Stage Breast Cancer

• Stage I-II (T1-2, N0-N1)• Management of the Breast

– Lumpectomy + Radiation– Mastectomy with or Without Reconstruction

• Management of the Axilla (Non-palpable nodes)– Sentinel node biopsy

Management of Locally Advanced Breast Cancer

• Stage III (anyT-N2+, T3-T4N0)– Tumour greater than 5cm– Inflammatory Breast cancer– Many nodes positive, palpable

• Management of the breast– Lumpectomy + radiation (small tumour, multiple

nodes positive)– Mastectomy with or without reconstruction more

common

Management of Locally advanced Breast Cancer

• Management of the Axilla– Palpable nodes

• Axillary Dissection (Level I and II)

– Non-palpable Nodes• Sentinel node biopsy

• Unresectable cancer– Neo-adjuvant chemotherapy for downstaging of

disease to make surgery possible

Inflammatory breast cancer

• Always Chemo first– If no response – 2nd line chemo– If no response – radiation

• In responders:– Always Modified Radical Mastectomy (Total

Mastetcomy and Axillary dissection)– NO Reconstruction

Lumpectomy

Oncoplastic lumpectomy with reduction

Oncoplastic lumpectomy with reduction

Mastectomy

• Anatomical landmarks

– Superior: Clavicle

– Medial: Sternum

– Lateral: Lat Dorsi

– Inferior: Inframmamary fold

Mastectomy

Skin Sparing Mastectomy

Skin Sparing Mastectomy

Skin sparing mastectomy with nipple reconstruction

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Nipple Sparing Mastectomy

Nipple sparing mastectomy

Sentinel node biopsy

• First few nodes that drain the breast

• Mainly a staging tool

• Inject radio-active colloid by nuc med and patent blue dye at the time of surgery to identify the sentinel nodes

• Avg of 1-4 nodes

• More than 4 does not give more info or change management

Take out:-Hot nodes-Blue nodes/ blue lymphatics-Palpable nodes

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Pectoralis minor

Level 1

Level 2

Level 3

Pathology - prognosis• Estrogen Receptors

– 80% breast cancers• Progesterone Receptors

• 65% breast cancer• Her 2-neu overexpression

• 15-18% breast cancers• Triple negative

• All receptors are negative (ER, PR, Her-2)• 15% breast cancers• Helps in determining prognosis and Management of the

patient with regards to adjuvant treatment (hormone therapy and chemo)

Biomarkers • These are not just prognostic but are predictive (of

response to specific therapies) • Current panel funded and required in Canada

Estrogen Receptor,Progesterone Receptor and Overexpression (or amplfication) of Her-2/neu

• For Prognosis Positive ER and PR correlate with better survival and are independent good prognostic indicators while overexpression of cell membrane Her 2/neu protein is a marker of poor prognosis

Hormone Receptors • Estrogens act on target tissues by binding to cell

proteins called estrogen receptors found in the nucleus of some types of cells.

• Only estrogen or close related proteins can bind. • When estrogen binds the receptor changes shape

and the hormone receptor complex binds to DNA sites near genes that are controlled by estrogen. These become active producing proteins that affect cell function

From National Cancer Institute

ER and PR can be on preneoplastic and invasive tumour cells

• The main effect of estrogen is not as tumour inducer but as a

promoter in carcinogenesis by increasing proliferation

• Also in fully neoplastic cells proliferation is often driven by estrogen.

• If ER present proliferation of tumour is tied to presence of functionally effective estrogen.

• Thus presence of ER on tumour cells predicts a response (inhibition) with blockade of or reduced production of estrogen

• PR is similar but a positive PR means functioning ER exists

Selective estrogen receptor modulators, or SERMs

• estrogen receptors of different target tissues vary in structure allowing estrogen-like drugs to interact differently ways in different tissues.

• selectively stimulate or inhibit the estrogen receptors

• Some drugs that block the action of estrogen in certain tissues actually can mimic the action of estrogen in other tissues.

Thus for Tamoxifen it blocks in breast or breast cancer cells

Testing

• This is now tested by immunohistochemistry tests.

• As this is a class II test the antibodies used should be approved and all steps of the test carefully controlled. This should include the obtaining and fixation of tissues and appropriate licensing / monitoring of labs

Adjuvant Radiation

• Indications – All lumpectomies should get adjuvant radiation

• What if had a mastectomy– 4 or more nodes positive– Tumour ≥ 5 cm

Adjuvant Treatment

• ER positive/Her-2 negative : Treat with hormonal therapy (Tamoxifen or an Aromatase Inhibitor)

• ER negative/Her-2 positive: Treat with Herceptin and chemo

• ER positive/Her-2 positive: Treat with Hormonal therapy and chemo and Herceptin

• Triple negative: chemo (cisplatin based)

Adjuvant ChemotherapyIndications:

– Node positive– HER-2 positive (≥5mm-1cm)– Triple Negative (≥5mm-1cm)– Relative: patients under 40 yo

• Decision making tools– www.adjuvantonline.com– Oncotype Dx, Mammaprint, PAM-50: ER positive

Node Negative

Recurrence

• Ipsilateral recurrence rates– 8 year accrued rate is 7% with negative margins, 14% with

focally positive margins, 27% with extensively positive margins

• Contralateral breast cancer rates– 2 to 11% – Risks: early age at initial diagnosis, family history, lobular

histology

• After salvage surgery, overall survival rates reported as 34% to 88% at 5 years and 57 to 69% at 10 years

OncoDx / Funded Molecular Test

RecurrenceScore®Result34The Findings are applicable to women who have stage I or II node negative, estrogen receptor positive (ER+) breast cancer and will be treated with 5 years of tamoxifen (tam). It is unknown whether the Findings apply to other patients outside these criteria.Clinical Experience: The following results are from a clinical validation study that included 651 patients from the NSABP B-20 study. The study included female patients with stage I or II, N–, ER+ breast cancer. Patients were randomized to either tam alone or tam plus CMF or MF chemotherapy. For patients in the pre-specified group with Recurrence Score results ≥ 31, the group average 10-year risks (95% CI) of distant recurrence were 40% (25%, 54%) for tam alone and 12% (6%, 18%) for tam + CMF/MF.1 Prediction of Chemotherapy Benefit after 5 Years of Tam,Based on the Recurrence Score Result (from NSABP B-20)Tam AloneTam + ChemoAbsolute Benefit of Chemotherapy at 10 Years by Recurrence Score

Microscopic Features of breast cancer in risk analysis and therapeutic options

• Tumour size• Tumour focality• Tumour margins• Tumour grade (Nottingham Histologic Score)• Lymphovascular invasion• Lymph node status• ER/PR/Her2 neu status

Nottingham Grading System To be reviewed on the 19th

Pathology ReportSPECIMEN SOURCE: 1. Right breast tissue -see margin inking colours2. left breast tissue long lateral short superior double deep3. Right axillary contentsCLINICAL HISTORY: ICARUS STUDY right breast invasive ductal cancer SP-14-037737left breast reduction - previous right invasive cancer SP-14-037737DIAGNOSIS:1. Right breast, lumpectomy: Invasive ductal carcinoma, grade 3/3, pT2 (4.5 cm)Closest margin 0.2 mm (deep)2. Left breast, reduction mammoplasty: No pathological abnormality3. Right axilla, lymph node dissection: Metastatic carcinoma in 4/16 nodes, pT2COMMENTS:IHC for ER PR HER2/neu was ordered on 1C

MICROSCOPIC DESCRIPTION:Block 1C shows some variation in appearance so IHC for markers was ordered on this block. The changes arehowever not related to grade just cytoplasmic featuresSPECIMENS(S) INVOLVED: 1: Right breast tissue -see margin inking coloursANGEL ARNAOUT, MDOTTAWA HOSPITAL501 SMYTH RDOTTAWA, ONTARIO K1H 8L6CANADAPage 1 of 6Printed Date: 2014-11-12Department of Pathology and Laboratory Medicine-Division of Anatomical Pathology-MRN: 06538102 Patient: MACDONALD, BETTY LYNN Accession #: SP-14-042915INVASIVE CARCINOMA OF THE BREAST: Complete Excision (Less Than Total Mastectomy, IncludingSpecimens Designated Biopsy, Lumpectomy, Quadrantectomy, and Partial Mastectomy With or WithoutAxillary Contents) and Mastectomy (Total, Modified Radical, Radical With or Without AxillaryContents)Radical, Radical With or Without Axillary Contents)

SPECIMENProcedure: Excision without wire-guided localizationLymph Node Sampling: Axillary dissection (partial or complete dissection)Specimen Laterality: RightTUMORDuctal Carcinoma In Situ (DCIS): DCIS is presentNegative for extensive intraductal component (EIC)Architectural Patterns: ComedoSolidNuclear Grade: Grade III (high)Necrosis: Present, central (expansive "comedo" necrosis)Lobular Carcinoma In Situ (LCIS): Not identifiedPresence of Invasive Carcinoma:Histologic Type of Invasive Carcinoma: Invasive ductal carcinoma (no special typeor not otherwise specified)Histologic Grade: Nottingham Histologic ScoreGlandular (Acinar) / Tubular Differentiation: Score 3: < 10% of tumor area forming glandular / tubular structuresNuclear Pleomorphism: Score 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderatevariability in both size and shapeMitotic RateScore 3 (>=8 mitoses per mm2)Overall Grade: Grade 3: scores of 8 or 9

EXTENTTumor Size / Focality:Tumor Size: Size of Largest Invasive Carcinoma: Greatest dimension of largest focus ofinvasion > 0.1 cm (cm)4.5cmAdditional Dimension (cm): 3.7cm x 2.5cmTumor Focality: Single focus of invasive carcinomaMacroscopic and Microscopic Extent of TumorSkin:Skin Invasion: Invasive carcinoma does not invade into the dermis or epidermisSkin Satellite Foci: Satellite foci not identifiedNipple DCIS: Not applicableSkeletal Muscle: Skeletal muscle is free of carcinomaMARGINSInvasive Carcinoma: Margins uninvolved by invasive carcinomaPage 2 of 6Printed Date: 2014-11-12Department of Pathology and Laboratory Medicine-Division of Anatomical Pathology-MRN: 06538102 Patient: MACDONALD, BETTY LYNN Accession #: SP-14-042915Distance from Closest Margin (mm): Specify (mm)0.2mmClosest Uninvolved Margin: PosteriorDuctal Carcinoma In Situ (DCIS): Margins uninvolved by DCIS (DCIS present)Distance of DCIS from Closest Margin (mm): Specify (mm)1mmClosest Uninvolved Margin: Posterior

ACCESSORY FINDINGSLymph-Vascular Invasion: PresentDermal Lymph-Vascular Invasion: Not identifiedTreatment Effect: Response to Presurgical (Neoadjuvant) Therapy: No known presurgical therapyLYMPH NODESTotal Number of Lymph Nodes Examined: Specify16Number of Lymph Nodes without Tumor Cells Identified: Specify12Number of Lymph Nodes with Isolated Tumor Cells: Specify0Micro / Macro Metastases: PresentNumber of Lymph Nodes with Macrometastases (> 2 mm): Specify4Number of Lymph Nodes with Micrometastases: Specify0Size of Largest Metastatic Deposit: Specify (mm)13mmExtranodal Extension: Not identifiedSentinel lymph node biopsy not performed

SPECIAL STUDIESEstrogen Receptor: PendingProgesterone Receptor: PendingHER2 (results for invasive carcinoma performed on this specimen or a prior core needle biopsy orincisional biopsy)HER2 Immunoperoxidase Results: PendingIn Situ Hybridization (FISH or CISH) for HER2 Results: Not performedSTAGE (pTNM)TNM Descriptors: Not applicablePrimary Tumor (Invasive Carcinoma) (pT): pT2: Tumor > 20 mm but <= 50 mm in greatest dimensionRegional Lymph Nodes (pN) (choose a category based on lymph nodes received with the specimen;immunohistochemistry and / or molecular studies are not required)Category (pN): pN2a: Metastases in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)Distant Metastasis (pM): Not applicable

• MOLECULAR MARKERS:

SPECIMENS(S) INVOLVED: 1: RIGHT BREAST

MICROSCOPIC DESCRIPTIONBlock Identifier: SP14-42627.1GDate of Surgery: 2014-10-27Date Received: 2014-11-03Date Test Performed: 2014-11-07• IHC for HER-2/neu overexpression• HERCEPTEST % positive cells: < 10 %• HERCEPTEST Intensity: +1• Control Slides (stained appropriately): Adequate

• HERCEPTEST (using FDA-approved conditions) Validated: 2012-05-21• FISH HER-2/neu amplification• Fluorescent in situ hybridization (FISH) HER-2/neu amplification: Not DoneISH positive HER2/neu definied as ASCO/CAP 2013:Either a) HER2 / Cep 17 ratio >2.0Or b) HER2 / Cep 17 ratio <2.0 but Average HER2 copy number =/>6.0 signals/cellISH Equivocal HER2/neu defined as (ASCO/CAP 2013):HER2 / Cep 17 ratio <2.0 but Average HER2 copy number =/> 4.0 and <6.0 signals/cell• Hormone receptors (Immunohistochemical method)• Hormone receptors (Immunohistochemical method): Internal control present/reactiveER: 67 - 100 %ER Average Intensity Score: IntermediatePR: 67 - 100 %PR Average Intensity Score: Strong• ER/PR positivity defined as > 1% tumour cell nuclei positive. Antibody sources: ER - Vector clone NCL-ER6F11; PR - Dako clone Pgr 636• Allred Score• ER: 7• PR: 8FINAL DIAGNOSIS• Diagnosis: Negative for HER-2/neu overexpression• ER: Positive• PR: Positive• Tissue Fixation Time: 8 - 100 hrs / validated in house

– Meets Guidelines• Pre-Fixation (Ischemic time): Optimal < 1 hour; maximum allowed 2 hours - validated in house

• Meets Guidelines

ORIHC for HER-2/neu overexpressionHERCEPTEST % positive cells: 10 - 30 %HERCEPTEST Intensity: +2Control Slides (stained appropriately): AdequateHERCEPTEST (using FDA-approved conditions) Validated: 2012-05-21FISH HER-2/neu amplificationFluorescent in situ hybridization (FISH) HER-2/neu amplification: Done

Reason for processing FISH: IHC results equivocalDone with Leica Her2 FISH System kit - Product code TA9217Average number of HER-2/neu signals per cell is: 1.8Average number of Cep 17 signals per cell is: 1.5Ratio of HER-2/neu to Cep 17 is:1.2Cells Counted: 601 observerISH positive HER2/neu definied as ASCO/CAP 2013:Either a) HER2 / Cep 17 ratio >2.0Or b) HER2 / Cep 17 ratio <2.0 but Average HER2 copy number =/>6.0 signals/cell---ISH Equivocal HER2/neu defined as (ASCO/CAP 2013):HER2 / Cep 17 ratio <2.0 but Average HER2 copy number =/> 4.0 and <6.0 signals/cell

FINAL DIAGNOSISDiagnosis: Negative for HER-2/neu ISHER: PositivePR: PositiveTissue Fixation Time: 8 - 100 hrs / validated in houseMeets GuidelinesPre-Fixation (Ischemic time): Optimal < 1 hour; maximum allowed 2 hours - validated in house

Meets GuidelinesCOMMENTSAll relevant controls stain appropriately.

Biopsychosocial Impact

• Life expectancy and impact on daughters• Insurance: disability, critical illness, life• Immediate vs. delayed reconstruction• Impact on partner and family members• Costs of treatment (parking, gas, food,

babysitters, hotels, etc.• Impact of gene testing• Impact on fertility

CLINICAL SCENARIO -1

• 70 year old woman 20 years post left sided mastectomy for breast cancer, presents to the ER with a bowel obstruction– What is your differential Dx?– Work-up?– Management?

Clinical Scenario - 2

• 50 year old woman presents with locally advanced breast cancer– What to look for on Clinical Exam?– Work-up and relevant lab findings?– Management strategies

• If resectable?• If not resectable?

Clinical Scenario -3

• 32 year old woman presents with a multi-centric breast cancer– Imaging?– What are your main concerns?

Clinical Scenario 4

• 28 year old woman comes to your office with palpable mass convinced she has breast cancer with clear imaging of fibroadenoma– What do you do?– What if was 55 years old?

Clinical Scenario 5

• 70 year old woman post bilateral mastectomies presents with recurrent disease in the chest wall– What to do?

Clinical Scenario 6

• 64 year old woman presents to the office with a large palpable axillary lymph node– Management and work-up?

Clinical Scenario 7

• Young woman refuses treatment for her locally advanced breast cancer

Clinical Scenario 8

• 58 year old woman post lumpectomy and SLN biopsy. Pathology shows:

• ER/PR/Her2 neu negative– 4 cm tumour– 1/24 lymph nodes positive– Negative metastatic workup

What is her prognosis?