breast 2 Flashcards
What are the cells of origin typically of a breast carcinoma?
ER positive cells
Explain the classification of breast carcinoma
Anatomical classification
lobule
duct
Pathological classification
insitu
invasive
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
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
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
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%
How to detect Paget cells?
cytological prep of exudate
nipple biopsy
What can Paget’s be mistaken for?
ECZEMA
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
How to manage DCIS
Wide local excision +/- radiotherapy Mastectomy Chemoprevention (Tamoxifen) Risk factors for recurrence Histologic grade Size Margins
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
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
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
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
Define invasive tubular car
Well differentiated, prominent tubules/ducts
Good prognosis
ER+, HER2-
Define invasive mucinous/colloid car
Abundant extracellular pools of mucin
Good prognosis
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
Define inflammatory cancer
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
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?
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
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?
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?
Path findings
Imaging studies showing mets or not
Clinical findings
What is the staging of the breast?
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%
