breast 2 Flashcards by Marie Francis

What are the cells of origin typically of a breast carcinoma?

ER positive cells

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Explain the classification of breast carcinoma

Anatomical classification
lobule
duct

Pathological classification
insitu
invasive

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What are the risk factors for carcinoma?

female
age (older age group)
family hx (BRCA1-chromosome 17 and BRCA 2 chromosome 13) 
obesity 
smoking
alcohol 
radiation exposure
late pregnancy 
late menopause
early menarche 
post menopausal oestrogen therapy 
OCP

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Differientiate invasive vs CIS

Invasive- penetrates the basement membrane and invades stroma

Carcinoma insitu- tumor cells are confined to the epithelium and do not penetrate the basement membrane

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Explain ductal carcinoma insitu

DCIS is a precursor to invasive carcinoma (esp w high grade DCIS)
malignant cells in TLDU confined to basement membrane
has many subtypes and comedo necrosis - high grade cells w central necrosis in duct w calcification has the worst prognosis
Other subtypes- cribiform, solid, papillary, micropapillary

Disease spectrum : atypical hyperplasia->low grade DSIS-> high grade DCIS
Also accumulation of genetic mutations

Associated with Paget’s Disease

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Define Paget’s Disease

Malignant cells arising from DCIS and extending
up the lactiferous ducts into the nipple skin without crossing the basement membrane

Presents as hyperaemia, ulceration of nipple and underlying lump in 50%

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How to detect Paget cells?

cytological prep of exudate

nipple biopsy

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What can Paget’s be mistaken for?

ECZEMA

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What are the factors for predicting the risk of progression to invasive malignancy?

Margins
Size of the lesion
Age of the patient
Grade of DCIS
80% of high grade lesions become invasive after 10 years if untreated
40% of intermediate grade lesions become invasive after 10 years if untreated
10% of low grade lesions become invasive after 10 years if untreated

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How to manage DCIS

Wide local excision +/- radiotherapy
Mastectomy
Chemoprevention (Tamoxifen)
Risk factors for recurrence
Histologic grade
Size
Margins

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Explain LCIS

abnormal cells fill lobules (diff from those in DCIS)
can be multifocal and bilateral
increased risk of developing invasive lobular AND ductal carcinoma in the same or contralateral breast

this is more frequent in younger women

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Classify invasive breast carcinomas

No special type -80%
invasive ductal car

Special type 
invasive lobular car -15%
invasive medullary car-3%
invasive mucinous car-3%
invasive papillary car
invasive tubular car

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How does invasive ductal car present?

production of duct like structure in desmoplastic stroma

macro: rock hard, immobile mass, irregular border, stellate appearance
micro: adenocarcinoma w desmoplastic stroma- scirrhous carcinoma

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How does invasive lobular car present?

macro: multifocal and bilateral
micro: cords invade in single file pattern - Indian filing - loss of E cadherin adhesion molecules
ER+ve
occurs in premenopausal women; morphologically distinct

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Define invasive tubular car

Well differentiated, prominent tubules/ducts
Good prognosis
ER+, HER2-

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Define invasive mucinous/colloid car

Abundant extracellular pools of mucin

Good prognosis

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Define medullary car

Circumscribed edge
Large malignant cells
Surrounding lymphocytic response
Slightly better prognosis than ca of non special type
ER-, PR-, HER2- (triple negative)
3% associated with BRCA1

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Define inflammatory cancer

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Any type of breast cancer that has infiltrated the dermal lymphatics
Red, swollen and oedematous breast
Associated with poor prognosis

Describe the spread of breast car

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Local – into surrounding breast tissue, chest wall and skin “Peau d’orange”
Lymphatic - axillary, internal mammary (carcinomas in the inner quadrants), ipsilateral supraclavicular nodes
Vascular - bone, lung, liver, brain
Trans-coelomic – pleural cavities
Recurrences may be local, regional (LN) or distant (systemic)

What is the presentation of a breast carcinoma?

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Lump
Other symptoms : 
changes in size and shape of breast 
skin ulceration(advanced cases)  
skin dimpling 
nipple inversion 
nipple discharge 
skin change 
arm swelling 
not usually a/w pain

Signs: 
inflammation (due to tumor)
skin dimpling 
mass (with asymmetry of nipples) 
peau d'orange 
nipple retraction esp if blood

List the metastatic features of breast cancer

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Symptoms: 
Breathing difficulties 
Bone pain or pathological fractures
Symptoms of hypercalcaemia 
Abdominal distension 
Jaundice 
Localizing neurologic signs 
Altered cognitive function

How does one assess the breast for malignancy?

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Triple Assessment
Clinical
Radiological
Pathological

Clinical
appropriate hx to assess presenting complaint and risk factors
inspection and palpation
check axillary nodes
Exam findings:
S2 – Benign findings
S3 – Findings are most likely benign but could be malignant
S4 – Findings are concering for malignancy
S5 – Most likely malignant findings

Radiological
U/S-preferred for younger <35
Mammogram- preferred for older >35
(MRI)

Pathology
FNA and core biopsy and open biopsy
FNA can be performed at outpatient , no anaesthesia, aspirate lump(solid or cystic) , staining, interpretation by cytologist : cytology (presence or absence of malignant cells)
advantages: cost effective
disadvantage: operator dependent and expertise in interpretation
does not distinguish invasive from non invasive

Needle core biopsy
–Guns -> thin cores of tissue/ small sample of tissue from lump
–Requires LA, slower, but easier to interpret, can be performed under X ray guidance
–Distinguishes in situ from invasive cancers

Open biopsy
–If uncertainty following triple assessment (not all elements of assessment in agreement)
–Possibility of intra-operative frozen section

Wire guided biopsy
Occasionally required to allow sampling of a radiological abnormality in order to provide a definitive tissue diagnosis

Needle placed under x-ray guidance into the area of abnormality

Needle acts as a guide to the surgeon

Performed under general anaesthetic
Exam findings for path: 
C1 or B1	no diagnosis possible
C2 or B2	benign
C3 or B3	atypia, probably benign
C4 or B4	suspicious for malignancy
C5 or B5 	malignant

What is the stage of breast carcinoma dependent on?

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Path findings
Imaging studies showing mets or not
Clinical findings

What is the staging of the breast?

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TNM

Stage I tumour less than 2 cm with no spread of disease.

Stage II tumour between 2 and 5 cm with mobile palpable lymph nodes.

Stage III tumour over 5 cm or locally advanced disease involving the chest wall or skin or fixed axillary nodal disease.

Stage IV metastatic disease.

What is the grading system for breast car?

Scarf Bloom Richardson

How is the grading assessed in breast car ?

``` mitotic count pleomorphic nuclei % tubule formation each given a score 1-3 where score for each category added where max score =9 , min score 3 Grades 1-3 1 :score of 3-5 2 :6-7 3 :8-9 ```

What are the prognostic factors a/w breast car?

Histologic grade Histologic subtype Stage Invasive/ non invasive Inflammatory carcinoma Expression of hormone receptors- er & progesterone +ve Expression of c-erb B2 (A/w EGFR) - more aggressive and poor prognosis, 20-30%

What does the prognosis of breast cancer depend on?

``` Angiogenesis Proliferative rate ploidy-DNA content genetic profiling Adequacy of excision Lymphovascular invasion ```

Describe breast cancer prognosis

Overall crude mortality 40% at 5 years, 60% at 10 years, continues rising - Recurrence/metastatic disease unpredictable 10 year survival - 70% if lymph node negative - 30% if lymph node positive Disease more aggressive in younger women Distant metastases - Median survival approximately 12-18 months

treatment of breast cancer

Surgery (mastectomy or breast conserving) Axilla- sentinel node/clearance -Sentinel lymph node biopsy if +ve- axillary clearance if -ve no need for axillary clearance -First lymph node draining site of cancer, most likely to be affected -Identified by dye or radio-isotope injected into tumour and then draining to lymph node Radiotherapy -Systemic therapy -Hormonal manipulation (tamoxifen, Arimidex, surgical or chemical ovarian ablation) -Tamoxifen(anti oestrogen) is associated with increased risk of venous thrombosis and endometrial ca -Trastuzumab (Herceptin) Aromatase inhibitors - most effective in post menopausal pts Chemotherapy Inhibition of angiogenesis consider in ALL node positive pts ; MDT setting Regimen: CMF- cyclophosphamide, methotrexate, 5-fluorouracil

What are the side effects for axillary clearance?

lymphoedema 20-40% | arm/axillary numbness 80%

What are the stromal tumors ?

fibroadenoma phyllodes sarcoma

Fibroadenoma typically affects?

young women after puberty but before 30

How does fibroadenoma present?

breast mouse- freely moveable, solitary well defined mass micro: fibrous stroma compressing glands - proliferation of connective tissue and epithelium responsive to oestrogen and progesterone thus affected by menstrual cycle pregnancy may cause increased growth regression after menopause

Phyllodes tumor more so occurs in?

older women >45

What is another name given to Phyllodes tumor?

giant fibroadenoma- same morphology as fibroadenoma but larger in diameter- 10-15cm

How does it Phyllodes tumor present?

large in size leaf like clefts and slits and thus are called cystosarcoma phyllodes can be both benign or malignant in malignant forms- high mitotic rate, nuclei pleomorphism and increased stromal cellularity seen has the tendency to recur locally but may mets (15%)

Uncommon tumours of the breast?

SARCOMAS angiosarcoma fibrosarcoma liposarcoma and mets; lymphoma, melanoma, carcinoma (lung, endometrium)

Which uncommon tumor is a/w a complication of radiotherapy?

angiosarcoma

Explain screening for breast cancer

the application of a test to detect potential cancer where no signs and symptoms are present detects cancer prior to systemic spread

What are the outcomes for screening?

Reduced mortality in the screened population when compared to the mortality rate in an equivalent unscreened population

What are the biases in screening?

Lead time bias apparent increase in survival time without reduction in mortality Length bias clinical outcome observations that are not adjusted for the rate of progression of disease Randomised controlled trials used to remove biases

Which age group should a screening mammogram be performed on ?

>50 years (50-64) every 2 years | reduces mortality up to 30%

breast 2 Flashcards

(43 cards)