BREAST Flashcards
1
Q
When to do genetic testing for BRCA?
A
PATIENT
- Ashkenazi Jew
- bilateral breast cancers
- male breast cancer
- triple negative breast cancer <40
FAMILY
- 3 relatives of any age with breast/ovarian cancer
- Male breast cancer
OTHER
- Manchester Score > 15 = 20% Chance of finding gene
2
Q
What are the indications for breat MRI?
A
SCREENING FOR BREAST CANCER
- high risk patients (BRCA, childhood Hodgkin’s lymphoma)
- Breast implants
PROVEN BREAST CANCER
- neoadjuvant chemotherapy (before/during/after to monitor disease progression)
- Lobular carcinoma (very difficult to detect LC on mammogram)
- Occult breast cancer (e.g. metastatic lymph node)
3
Q
What are the causes of nipple discharge?
A
Physiological
- Hormonal variation
- Pregnancy/Post lactational
- Mechanical stimulation
- Galactorrhea
- Duct ectasia /periductal mastitis
Pharmacological
- Oestrogens/Progestrogen
- Long term opiates
- Antidepressants
- Antipyschotics
- Metachlopramide
Pathological
- papilloma
- duct ectasia
- breast cancer
- paget’s disease
4
Q
How do you manage nipple discharge?
A
Abnormal pathology
- treat as cause
Normal pathology
- single duct (not clear) = microdochectomy
- multiple duct = subareolar excision (Hadfield’s)
5
Q
Causes of gynaecomastia
A
-
Physiological
- high serum oestradiol:testosterone (neonates, puberty, elderly)
-
Pharmacological
- Recreational = marijuana, anabolic steroids
- hormonal inhibitors = spirinolactone
- secondary hyperprolactinemia = TCA, metoclopramide
-
Pathological
- Either problem with oestrogen or testosterone
- oestrogen production increased = tumours (pituatry, testicular, adrenal), paraneoplastic syndrome (bronchial cancer)
- reduced oestrogen clearance = cirrhosis, haemachromatosis,
- reduced testosterone production = Klinfelters, cryptochordism,
6
Q
What is Phyllodes tumour?
A
A stromal fibro-epithelial neoplasm whereby 90% are benign however 10% are malignant.
Presents as a rapidly growing breast mass
7
Q
What is the difference between benign and malignant Phyllodes tumour?
A
It is the stromal component that determines malignant potential
Malignant
- stromal cellularity and mitotic rate are high
- infiltrative tumour margin
- sarcoma like behaviour - metstasize to lung and NOT LNs
8
Q
Managment of Phyllodes tumour
A
MDT discussion
Breast = Main treatment
- Excision with negative margins (R0) – 1 cm
- BCT is sufficient as long as can achieve margin
- Mastectomy if cannot achieve adequate margin
Axilla
- Rarely spread to lymph nodes therefore SLNBx or ALND is not recommended (even for malignant tumours)
Adjuvant XRT
- Borderline or malignant phyllodes
Systemic therapy
- No role for hormonal therapy.
- Controversial role for chemo, however consider if
- Size > 5cm
- Malignant
9
Q
What is Paget’s disease of the nipple?
A
Eczematous and inflammatory change involving the nipple/areolar complex
Histologically
- large pale staining cells with prominent ovoid nucleoli
- pathological hallmark = Paget’s cells (intra-epithelial cells) in the epidermis
10
Q
What are the pathogenesis theories of Paget’s disease?
A
2 main theories exist
migration (epidermotrophic)
- ductal cells migrate from the basement membrane of the ducts into the nipple epidermis.
transformation
- Paget’s cells arise from transformed malignant keratinocytes (Toker cells).
11
Q
How do you treat mammary Paget’s disease?
A
Triple assessment;
It can harbor underlying carcinoma (invasive or in-situ) in 85-90% of cases and clinically/radiologically – often normal
Confirm diagnosis
- core biopsy (or full thickness wedge biopsy) of nipple
Imaging
- Mammogram with magnified views of the subareolar region and Ultrasound (breast + axilla)
- MRI breast if mammographically normal
Breast
- (Simple) Mastectomy + SLNBx = diffuse disease or disease at a distance from nipple
- BCT (WLE) of nipple/ducts with adjuvant radiotherapy = disease localized to nipple areolar complex.
Axilla
The risk of axillary metastases is higher in women with invasive cancer and a palpable mass
The management of the axilla is the same as for any breast cancer
SLNBx indications
- Clinically node negative
- Synchronous with mastectomy
- Invasive cancer identified (but clinically impalpable breast lesion)
- ALND* indications
- Clinically node positive (FNA proven)
Systemic Therapy
- Limited evidence regarding efficacy of tamoxifen in Paget’s disease
- Unclear if reduces local recurrence rates
- should be based solely upon the characteristics of any associated ductal carcinoma
12
Q
What is the pathological definition for DCIS and high grade DCIS?
A
General
- Pre-invasive, in-situ lesion of the breast where malignant epithelial cells are found confined within the basement membrane.
- 5 types of DCIS are = comedo, cribiform, papillary/micropapillary and solid.
High-grade
- Large pleomorphic nucleoli are large (>3 x size of RBC)
- coarse/clumped chromatin
- frequent mitoses and high proliferative rate
- Comedonecrosis usually present but not required
13
Q
Why shouldn’t you use methylene blue dye for a SLNBx if a patient is also taking psychiatric medications?
A
- Methylene blue inhibits the action of monoamine oxidase A
- enzyme responsible for breaking down serotonin in the brain.
- Toxic levels of serotonin can build up in the brain when methylene blue is given to patients taking serotonergic psychiatric medications.
- serotonin syndrome
14
Q
What are the indications for mastectomy in DCIS?
A
- multifocal DCIS (if adequate excision cannot be achieved with a cosmetically acceptable outcome)
- widespread calcification
- Persistently positive margins (after re-excision)
- Paget’s disease
- Patient preference
15
Q
What are the indications for SLNBx in DCIS?
A
- Undergoing mastectomy
- Palpable mass
- Size > 5cm
- Biopsy findings (high grade, microinvasion, comedonecrosis)
16
Q
What is the 21-Recurrence Score/Oncotype-DX?
A
21-gene Recurrence Score (RS) = Oncotype-DX has both prognostic (risk of cancer recurrence) and predictive value (benefit of chemotherapy)
indications
- for hormone receptor positive but node negative early breast cancer (i.e. stage I/II).
Use of score
- to see whether chemotherapy in addition to endocrine therapy is of any benefit for ER positive but HER-2/node-negative patients.
- If RS>31 then there is a benefit of adjuvant chemo.
17
Q
What is the Z-11 criteria?
A
Early breast cancer is defined as the inclusion criteria for Z-11
- T1/T2 (i.e. <5 cm)
- Clinically node negative
- Only 1-2 positive SLN
- No extracapsular spread
- Undergoing breast conserving surgery followed by adjuvant whole breast radiotherapy (WBRT)
18
Q
Positive Z-11 Criteria
A
- If Z-11 criteria fullfilled then can omit AXLND
- Z-11 trial showed no difference in 5-year overall survival or 5-year disease free survival or local recurrence between the two groups (AXLND vs. SLNB alone).
- Many patients in Z-11 were ER-positive.
- Hypothesis for no statistical difference between the two could be that adjuvant WBRT can treat the axilla.
19
Q
when do you give XRT after mastectomy?
A
- size > 5 cm (T4,T3)
- LNs involved > 4
- positive deep margins
- undergone neoadjuvant chemotherapy
20
Q
What is HER-2?
A
- HER-2 is a human epidermal growth factor receptor.
- It is 1 of 4 tyrosine kinase receptors (HER 1,2,3 & 4) in the EGFR family.
- It is a proto-oncogene located at the long arm of chromosome 17
- Structurally the receptor is comprised of 3 parts
- Extracellular domain
- Transmembrane domain
- Intracellular domain
21
Q
How does HER-2 work?
A
- HER-2 can dimerise (or pair) with any of the other 4 receptors however HER-2 and HER-3 pairing has the strongest mitogenic potential
- Once the receptor is activated it promotes cancer cell survival via different patwhays
- MAPK – promotes proliferation
- PI3K – inhibits apoptosis
- 1 in 4 breast cancer patients (25%) will overexpress HER-2 which results in uncontrolled proliferative and anti-apoptotic signals.
22
Q
How do you manage ADH?
A
Hookwire localization excisional biopsy
- positive for adjacent cancer = treat as appropriate
- negative (ie only ADH) = risk reduction therapy only (ie. further surgery not required
Risk reduction
- chemoprevention with SERM (tamoxifen)
- surveillance
23
Q
How is LCIS managed?
A
- 3-15% risk of adjacent malignancy in either breast
- often multicentric/multifocal/bilateral (up to 60%)
- If LCIS is picked up incidentally in otherwise benign breast tissue then excisional biopsy recommened to exclude underlying invasive breast cancer or DCIS.
two types of LCIS are classical and pleomorphic (latter LCIS carries a higher risk of malignancy)
- Classical LCIS = margins not relevant. Just ensure no invasive cancer.
- Pleomorphic LCIS = excision to clear margins.
24
Q
What are the indications for neoadjuvant chemotherapy in breast cancer?
A
- T4 (skin/wall involvement, IBC)
- large multicentric
25
What is the key step to do before commencing NACT for breast cancer patients?
Key step: place clip in tumour bed before initiation of NACT in case of complete response
If complete response occurs and patient is taken to theatre, then at least clip serves as a marking for where original tumour was.
26
Who do you give radiotherapy tumour boost to?
**high-risk factors for recurrence**
* younger than 50 years
* pathologically involved axillary nodes
* lymphovascular space invasion
* and/or close or positive resection margins).
Given after WBRT if patient fulfils above
27
What is the managment of the axilla in NACT?
Clinically node positive
* FNA before initiating NACT
* ALND if positive
Clinically node negative
* SLNB after chemo.
* If unable to identify SLNB then there is **no role for random sampling**. Must proceed to ALND.
28
What are the options for NACT in patients with operable HER-2 positive breast cancer?
Can give **pertuzamab** (HER-2 dimerization inhibitor) in addition to trastuzamab
29
What are the different subtypes of DCIS and how do you distinguish them histologically?
* **solid** - ducts pluged with cancer cells
* **cribiform** - gaps between cancer cells
* **papillary/micropapillary** - finger like projections into lumen
* **comedonecrosis** - duct plugged with dead cells
30
Why shouldn't you inject methylene blue superficially?
* should be deeply injected
* may cause severe **necrosis** upon **intradermal** administration
31
Which patients are considered high risk for breast cancer?
As from NBOC Australia
Two 1° or 2° relatives on one side of the family diagnosed with breast or ovarian cancer plus one or
more of the following
* breast cancer diagnosed before the age of 40
* bilateral breast cancer
* breast and ovarian cancer in the same woman
* Jewish ancestry
* breast cancer in a male relative.
Member of a family in which the presence of a high-risk breast cancer gene mutation has been established.
32
What genetic mutations are associated with hereditary breast cancer?
* BRCA mutations
* TP53: Mutations cause Li-Fraumeni syndrome. It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene.
* PTEN: Mutations cause Cowden syndrome, which produces hamartomas (benign polyps) in the colon, skin growths, and other clinical signs, as well as an increased risk for many cancers.[2]
* CDH1: Mutations are associated with lobular breast cancer and gastric cancer.[2]
* STK11: Mutations produce Peutz–Jeghers syndrome. It is extremely rare, and creates a predisposition to breast cancer, intestinal cancer, and pancreatic cancer.[2]
33
What are the contraindications to SLNBx in breast cancer?
BREAST
* inflammatory breast cancer
* multifocal tumours
* DCIS (usually)
AXILLA
* clinically suspicious axillary nodes/biopsy-proven, node-positive disease
PATIENT FACTORS
* pregnant
