Breast Flashcards
Categorise the causes of Nipple Discharge
- Physiological
- normal in pregnancy & lactation
- milky discharge may occur transiently in neonate
- bilateral multiduct green/white/brown/blue/black discharge can be physiological, natural secretion from apocrine glands in ducts, usu from multiple ducts
- Intraductal
- Single duct
- Papilloma
- DCIS/malignancy (rare)
- Multiple ducts
- Multiple papilloma (increased risk of malignant change)
- Mammary duct ectasia (though this can be considered aberration of involution)
- Breast infection
- Single duct
- Galactorrhoea (some causes include physiological and drugs)
- True galactorrhoea = a copious milky discharge not assoc w pregnancy or breastfeeding = rare & usually drug induced
- Drugs that change DA activity: haloperidol, metoclopramide, chlorpromazine, opiates, COC
- PRL due to: primary PRL-secreting tumour (pituitary or lung cancers)
- hypothyroidism - increased TSH can stimulate prolactin release
- chronic renal failure - ~30% these pts have elevated prolactin
- Traumatic
- Paget’s
- Nipple eczema
Categorise the factors affecting local recurrence after BCT.
- Tumour factors
- Margins are most important factor
- Histological grade
- LVI
- Extensive in situ component controversial – probably not
- Size and histological subtype do not affect
- Multiple tumours - no increase in LR if all excised
- Patient factors
- More common in younger pts
- Family history increases LR
- LR less frequent in pts w larger breasts
- Adjuvant treatment (radiotherapy +/- endocrine, chemotherapy) reduces recurrence rate
Categorise the factors influencing the cosmetic outcome after BCT.
Patient factors:
- Small breast and very large breast problematic
- Smoking
- Age is correlated with poorer outcome
Tumour factors:
- Locations of tumour; best in upper outer (45%)
- Central difficult to reconstruct
Surgical factors:
- The volume of breast tissue excised is the most important factor affecting cosmesis (>10% bad)
- Re-excision
- Axillary surgery associated with poorer cosmetic outcome
- Post-operative complications
Categorise the side effects of radiotherapy
Early:
- Systemic side effects - nausea, lethargy
- Erythema
- Oedema
- Soft tissue necrosis
- Decreased mobility
- Tissue fibrosis
Late: (think of long term damage to nearby structures)
- Rib #
- Pneumonitis
- Induced cancers
- Vasculitis
- Cardiomyopathy
- Brachial plexopathy
Classify the causes of granulomatous mastitis
- Primary
- Idiopathic
- ?Autoimmune
- ?Associated with cornybacterium
- Secondary
- Systemic granulomatous disease
- Wegener’s
- Sarcoidosis
- Granulomatous infection
- TB
- Histoplasmosis
- Systemic granulomatous disease
Classify the causes of mastalgia
- Non-breast pain (<2%)
- Costochondritis (“Tietze’s syndrome”)
- Rib injury
- Cervical root syndromes
- Angina
- GORD
- Mondor’s disease (cording superficial thrombophlebitis)
- Cyclical mastalgia (60%)
- Pre-menstrual crescendo
- Non-cyclical mastalgia (40%)
- Pregnancy
- Breast cysts/abscesses
- Sclerosing adenosis
- Cancer
Decribe the classification of deformity following breast conserving surgery.
Described by Clough et al:
- Type I
- Patients have a treated breast with a normal appearance but there is asymmetry between the two breasts
- Type II
- Patients have a deformity of the treated breast. This deformity can be addressed with partial breast reconstruction.
- Type III
- Patients have a severe deformity or diffuse painful fibrosis. This can only be treated with mastectomy +/- reconstruction.
Describe the classification of capsular contraction following breast implant surgery.
- Grade I (absent)
- The breast is soft with no palpable capsule and looks normal
- Grade II (minimal)
- The breast is slightly firm, with a palpable capsule but looks normal
- Grade III (moderate)
- The breast is firm with an easily palpable capsule and looks abnormal
- Grade IV (severe)
- The breast is hard, cold, painful, and distorted.
Describe the molecular classification of breast cancer
- Luminal A
- ER/PR +, Her2-, low Ki67
- <15% have p53 mutation
- Less aggressive; respond to hormone therapy
- Luminal B
- ER/PR+, HER2+/-, high Ki67
- 30% have p53 mutation
- More aggressive; high benefit of tailored therapy
- Basal-like:
- Most diverse and discussed
- Usually triple negative
- Most have p53 mutation
- Younger women, ethnic predisposition
- Treat with Anthracycline, Taxanes, maybe platinum-based
- Scope for anti EGFR modality therapy
- HER2 enriched
- HER2 positive
- ~75% have p53 mutation
- Respond well to Herceptin and chemo
Describe the Nottingham Prognostic Index and state 10-year survivals for each of the categories.
Pathological size (cm) x 0.2
+ Lymph node stage (1, 2, or 3)
+ Grade (1, 2, or 3)
- NPI 2.02-2.4 (excellent) = 96%
- NPI 2.41-3.4 (good) = 93%
- NPI 3.41-4.4 (mod1) = 81%
- NPI 4.41-5.4 (mod2) = 74%
- NPI 5.41-6.4 (poor) = 55%
- NPI 6.41-6.8 (v poor) = 38%
Describe the sclerotic/fibrotic lesions of the breast.
- These are histologically termed diagnoses which are proliferative lesions without atypia
- Confer small risk of breast ca cf general population (1.5-2xRR)
- Sclerosing adenosis
- Lobular lesion with increased fibrous tissue and interspersed glandular cells
- Differs from radial scars & CSLs histologically in degree of excessive myoepithelial proliferation seen together w fibrosis
- Can present as mass or suspicious finding on mamm (can be assoc w deposition of calcium)
- Radial scar
- Elastic/collagen stellate nidus w entrapped epithelial cells
- <10mm
- usually asymptomatic/incidental on biopsy; sometimes can be detected on mamm as suspicious spiculated mass; rarely present as palpable mass
- Complex sclerosing lesion
- Similar to radial scar but >10mm and less organized histologically
- As above usually asymptomatic
Describe your approach to management of a patient with gestational breast cancer.
- Gestational breast cancer is defined as breast cancer that is diagnosed during pregnancy, in the first postpartum year, or any time during lactation.
- Gestational breast cancer presents a challenging clinical situation, since the welfare of both the mother and the fetus must be taken into account.
- The tenets of breast cancer management remain the same with some modifications
- Manage the breast
- Manage the axilla
- Manage systemic disease
- Consider reconstruction and psychosocial welfare
- Minimise harm to the foetus but treatment of breast cancer shouldn’t be unnecessarily delayed because of pregnancy
- Evaluate for distant disease as for non-pregnant woman but can attenuate to include CXR with fetal shielding, USS or MRI of liver and MRI spine with contrast to evaluate for bone mets
- Breast and axillary surgery appear to be safe in pregnancy in any trimester
- mastectomy may be chosen if early in the pregnancy as RT is contraindicated (causes pregnancy loss, malformation, disturbances of growth or development and mutagenic and carcinogenic effects)
- otherwise can have BCS and RT given after delivery, or if candidate for neoadjuvant chemo (AC or FAC) which is safe in second and third trimesters (see below), surgery can be delayed til after that
- AND is standard of care at present; SLNB controversial due to limited evidence (effect of pregnancy on SNB drainage is unclear)
- reconstruction delayed til after delivery
- Radiation therapy is contraindicated in pregnancy
- AC or FAC chemotherapy is safe in the second and third trimesters (low incidence of congenital malformations but has been assoc w IUGR, prematurity and low birth weight in ~1/2 exposed infants); whereas in first trimester, 15-20% foetal loss
- advice is to not delay initiation of systemic chemo once the pregnancy has reached second trimester, if indicated (for adjuvant or neoadjuvant purposes)
- Herceptin is contraindicated in pregnancy
- Endocrine therapy is contraindicated in pregnancy
Discuss risk classification based on gene expression profiling in breast cancer.
Gene expression profiling is a relatively new technology that assesses the tumour at a genetic level to further understand its biological behaviour and help oncologists decide whether chemotherapy is needed or could safely be avoided.
AN example of a gene expression profiling test is Oncotype-Dx. This is a molecular diagnostic test which predicts the likelihood of a patient’s tumour recurring over a ten year period. It analyses 21 genes in the tumour and develops a three tier recurrence score between 0 and 100.
If the Recurrence Score is:
lower than 18: There is a low risk of recurrence. The benefit of chemotherapy treatment is likely to be small and outweighed by the risk of side effects.
18 up to and including 30: There is an intermediate risk of recurrence and it’s not clear whether the chemotherapy benefits are greater than the risks of side effects. The TAILORx trial has demonstrated that this group can now safely avoid chemotherapy to no detriment!
greater than or equal to 31: There is a high risk of recurrence and the benefits of chemotherapy are likely to be greater than the risks of side effects.
Discuss the distribution of the causes of gynaecomastia
PIPP
- Physiological – 20% - trimodal distribution
- Conditions where there’s natural increase in oestrogen:testosterone ratio - neonate, puberty, elderly
- Idiopathic – 20-25%
- Pharmacological – 20-30%
- Hormone supplements (oestrogens, anabolic steroids, anti-androgens)
- Anti-androgens or androgen-blocking drugs e.g. spironolactone
- Other cardiac drugs eg digoxin, ACEIs, amiodarone
- Drugs that cause hyperprolactinaemia eg metoclopramide
- Recreational drugs eg marijuana, opiates
- Pathological – 35%
- Increased oestrogen production by a tumour <3% (can produces oestrogens, androgens, aromatase or bHCG) – hepatomas, testicular tumours, pituitary tumours, adrenal tumours, paraneoplastic syndrome assoc w bronchial carcinoma
- Systemic illness – renal failure, liver failure (decreased oestrogen clearance by liver), hypo/hyperthyroidism (increased aromatisation of androgen into oestrogens in hyperthyroidism), obesity (increased aromatisation)
- Endocrine conditions
- decreased natural testosterone production/primary hypogonadism – Klinefelter’s most common
- secondary hypogonadism/testicular failure – eg damage to testes from mumps orchitis, bilateral cryptorchidism, radiotherapy or hypopituitarism
- androgen insensitivity
- acromegaly
Discuss the types and management of proliferative breast lesions with atypia, include reference to “upgrade” rates.
- (epithelial hyperplasia = increase no of cells lining ducts
- mild ductal hyperplasia = no of epithelial cells within a duct relative to normal (2-5 cells in depth) à observation, normal surveillance)
- florid ductal hyperplasia = no of epithelial cells occupying ≥70% of duct lumen w cytological features of benign cells à observation, normal surveillance))
- ADH )
- ADH = proliferation of uniform epithelial cells lining duct with cellular atypia; looks microscopically like low grade DCIS in terms of cellular & architectural atypia but <2-3mm or involving (completely filling) <2 ducts
- Upgrade rate 10-20%; excise
- RR breast ca 4-5x – surveillance, ?offer chemoprevention)
- ALH = proliferation of monomorphic, evenly space, discohesive cells filling but not expanding the involved lobules; shares cytologic & architectural features w LCIS but quantitatively lesser in extent; <50% acini expanded by these cells
- Upgrade rate , low <3% - don’t excise unless discordance
- RR breast ca 4-5x – surveillance, ?offer chemoprevention
- LCIS = non-invasive lesion that arises from lobules & terminal ducts of breast; monomorphic proliferation of discohesive cells in >50% of total number of acini in TDLU
- Not considered a breast ca but rather a histological marker for breast ca risk
- Classic LCIS upgrade rate v low <3% - don’t excise unless discordant
- Pleomorphic or florid LCIS upgrade rate 17-46% - excise to clear margins
- RR 7-11x – surveillance, ?offer chemoprevention
Discuss your approach to management of BRCA1 and BRCA2 positive patients
- Risk assessment and counselling
- Familial genetic testing
- Risk counselling
- Education
- High-risk screening
- Self examination from 18
- MRI/USS from 25-29
- MRI/Mamm/USS from 30-75
- ?TV USS and Ca-125
- Risk reduction
- SERMs reduce risk by ~40%
- RRM reduce risk by ~95%
- Risk-reducing Salpingo-oophorectomy also reduces risk of breast cancer by ~50%
Family history that would mandate genetic testing in breast cancer
Two first or second degree relatives diagnosed with breast or ovarian cancer PLUS one or more of the following on the same side of the family:
Additional relative(s) with breast or ovarian cancer
Breast cancer diagnosed under 40
More than one primary breast cancer in the same woman
Breast and ovarian cancer in the same woman
Ashkenazi (Eastern European) Jewish ancestry
Male breast cancer
Give an overview of benign breast disease in histological terms.
- Non-proliferative breast lesions
- Simple cysts
- Galactocele
- Mild ductal hyperplasia
- Simple columnar alteration
- Proliferative breast lesions without atypia
- Florid ductal hyperplasia
- Columnar hyperplasia
- Fibroadenomas
- Adenoma
- PASH
- Sclerosing adenosis
- Radial scars/comple sclerosing lesions
- Papilloma
- Proliferative breast lesions with atypia
- Atypical ductal hyperplasia
- Flat epithelial atypia
- Atypical lobular hyperplasia
- Lobular carcinoma in situ
- Atypical papilloma
How are breast cysts classified and what is the respective management?
- Simple breast cysts
- Asymptomatic should be left alone
- Large, symptomatic cysts can be aspirated to dryness
- If aspirated and a mass persists - triple assessment
- Complicated/complex cysts
- Thin or thick septations
- Internal echoes
- No posterior enhancement
- Thickened/irregular wall
- Need aspiration and cytology and biopsy of thickened area.
How are fibroadenomata classified?
- Simple
- Complex – contain other proliferative changes eg sclerosing adenosis, ductal epithelial hyperplasia, epithelial calcification or papillary apocrine changes (may be associated with calcifications or cysts >3mm)
- Giant >5-10cm
- Juvenile fibroadenomata (age 10-18)
How can benign breast disease be classified?
- Congenital abnormalities – supranumerary nipples, accessory breast tissue, breast hypoplasia
- ANDI
- Breast development <25 – fibroadenomas, tubular & lactating adenoma, macromastia
- Early reproductive 25-35 – cyclical pain & nodularity
- Involution 35-555 – palpable breast cysts, sclerotic/fibrotic lesions, duct ectasia
- Benign neoplasms & proliferations
- Columnar changes
- Epithelial hyperplasia, ADH
- Ductal papillomas
- Phyllodes
- Lipomas
- Granular cell tumours
- Infection
- Neonatal infections
- Lactational
- Non-lactational infections – periareolar infections, MDF
- Post-surgical/implant associated infections
- Other including traumatic, Mondor’s disease, gynaecomastia, diabetic mastopathy
How common is pathological response following NAC in breast cancer?
How is it classified?
Approximately 80% of patients have a clinical response; ~35% have complete clinical response, ~45% have a partial clinical repsonse. Complete pathological response occurs in ~13%.
The Miller-Payne classification is used.
How is DCIS classified?
- Histological sub-types:
- Comedo (worse prognosis)
- Non-comedo
- Solid
- Micropapillary
- Papillary
- Cribriform
- Clinging
- Histological grade:
- Based on nuclear polymorphism, nuclear atypia, and mitotic rate into low, intermediate, or high grade.
How is non-metastatic breast cancer classified?
Nonmetastatic breast cancer is broadly considered in two categories:
- Early stage – This includes patients with stage I, IIA, or a subset of stage IIB disease (T2N1).
- Locally advanced – This includes a subset of patients with stage IIB disease (T3N0) and patients with stage IIIA to IIIC disease.
How is the malignant potential of phyllodes histologically classified into bening, borderline and malignant?
- Classified as benign, borderline or malignant based on
- degree of stromal cellularity and atypia
- mitotic activity (<4, 4-9 or >10 per 10HPF)
- infiltrative or circumscribed tumour margins
- presence/absence of stromal overgrowth (presence of pure stroma devoid of epithelium most consistently assoc w aggressive (metastatic) behaviour - present in malignant but not in benign or borderline
- these three groups have local recurrence rates of 8%, 13% and 18%; but margin status is also important in terms of recurrence risk
How is tumour grade in breast cancer graded?
(irrespective of histological type)
The Nottingham method. Assessment of grade considers tubule formation, nuclear pleomorphism, and mitotic count. Each category is given a score of 1-3.
Grade 1 - well differentiated = 3-5 points
Grade II - moderately differentiated = 6-7 points
Grade III - poorly differentiated = 8-9 points
In patients with positive sentinel lymph node biopsy for breast cancer staging, what criteria must be fulfilled in order to justify witholding axillary lymph node dissection?
Based on the inclusion criteria for the ACOSOG Z0011 and AMAROS trials:
- T1 or T2 disease
- 1 or 2 sentinel lymph nodes positive
- Breast conserving surgery
- Whole breast irradiation planned
- No pre-op chemotherapy
In what potential DCIS cases can Radiotherapy be omitted?
Low- or intermediate-grade, small (<2.5 cm in size), and resected with widely negative margins (≥1 cm).
Consider more in older people.
Indications of adjuvant Rx to chest wall post Mx
- pT3N+, pT4Nany, pTanyN2/3
- Consider for pT1-2N1, pT3N0 depending upon presence of additional risk factors*
- Positive surgical margins
- Inflammatory breast cancer
*Additional risk factors for locoregional recurrence include:
LVI
high tumour grade
multifocal or multicentric tumours
nodal burden
young age
ER negative
Outline your management approach to mastalgia
- Exclude underlying disease process
- Simple measures:
- Wear soft, supportive bra 24/7
- Simple analgesia including topical NSAIDS
- Maintain healthy weight
- ?Reduce caffeine and fat
- Change OCP
- Medical therapy:
- Evening primrose oil; no RCTs but anecdotally used
- Danazol - androgenic - worse than…
- Tamoxifen:
- 10mg po od 3-6 months
- Response in up to 70%
- Take during luteal phase to reduce S/E
Personal Hx that would mandate genetic testing
BREAST (6)
- Breast cancer diagnosed <40yrs
- Triple negative ≤50yrs
- Triple negative any age when there is a close relative with breast or ovarian cancer
- Two or more primary cancers when first occurred <60yrs
- Lobular breast cancer and fhx of lobular breast or diffuse type gastric carcinoma
- Breast cancer plus personal or family history of: - Peutz Jegher syndrome, PTEN hamartoma syndrome (Cowdens), Li Fraumeni syndrome, ATM
OVARY (1)
High grade, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer
SEX (1)
Male breast cancer diagnosed at any age
BREAST and OVARY (1)
Breast and ovarian cancer primary cancers at any age
Provide an evidence based stance of “isolated tumour cells” and “micromets” in breast cancer.
Prognostically, patients with isolated tumor cell clusters appear to do as well as patients without any pathologic node involvement.
Patients with pN1mi breast cancer have a slightly worse prognosis compared with those with node-negative breast cancer, but micrometastases do not predict recurrence.
The results of the MIROR study (Micrometastases and Isolated tumour cells, Robust Or Rubbish?) described occult mets as having a small statistically increased risk of death, distant disease, and “events” ?clinical relevance.
