Breast Cancer FRCR C02A Flashcards
How is each breast divided?
5 regions
1. Central and
2. UOQ
3. UIQ
4. LOQ
5. LIQ
What’s the Lymphatic Drainage of Breast?
Axillary LNs
IMNs
What are the types of cancer affecting Breast?
Invasive ductal carcinoma
Invasive lobular carcinoma
what’s the status of E-cadherin in IDC and ILC?
+ in IDC
- in ILC
What are the reasons for improvement in 5 yr OS for Breast Cancer?
- screening
- improved treatment (sugical techniques, adjuvant Hormone Rx and better ChT)
what are the RFs for Breast Cancer?
- Age
- Reproductive factors
- History of Benign disease
- Previous Radiation exposure
- Dietary factors
- Genetic Factors
How does age affect Breast cancer risk?
Incidence increases with age, X2 every 10 yrs until menopause, then rate slows
What Reproductive Factors are a/w BC?
- Early menarche
- Late natural menopause
- Late age at 1st birth
- nulliparity
B/L Oophorectomy b4 age of 35: reduced risk of BC
How are exogenous hormones a/w BC?
Estrogen and Progesterone in combination Increases risk more than taking Estrogen alone,
increases with increasing length of HRT use
Does HRT in BC pts affect risk of recurrence?
Yes,
HABITS trial has shown that
What Dietary FActors are a/w BC?
- Obesity
- Alcohol intake
Does obesity in premenopausal women increase risk of BC?
No in fact studies have shown it reduces
But it increases risk in Post menopausal women by about 50 %
How does family Hx affect risk of BC?
1st degree relative with BC: doubled
if >1, 1st degree relative, higher risk or has BC at young age
Mutations in which genes are a/w Familial BC?
BRCA 1 and 2, TP53
where is BRCA 1 located, how much does it Increase risk of BC?
chromosome 17q21
35 to 85 %
what are features of BRCA 1 associated BC?
young age
increased risk of ovarian cancer
more malignant pathological features
Typically TNBC
Where is BRCA2 gene located?
Chromosome arm 13q
By what % BC risk is increased with BRCA 2 +?
20 to 60 %
what are other cancers BRCA 2 associated?
Male: PRostate
pancreas and bladder cancer
NHL,
What’s peculiar about BRCA 2 associated BC?
ER and PR +, higher grade with less tubule formation
What is TP53, % of increased BC risk, location?
17p13
Li Fraumeni Syndrome
50% risk of developing BC
what other genetic syndromes are a/w BC?
Ataxia Telengiectasia (AR )
Cowden’s Syndrome (AD) (PTEN)
Muir Torre Syndrome
Peutz Jeghers Syndrome
what’s the histology of BC?
almost all Adenocarcinoma
Location wise incidence of BC?
UOQ 50%
Central 20 %
UIQ 10%
LIQ 10 %
LOQ 10%
How is BC graded ?
Bloom Richardson system modification
Grade is based on
1. degree of tubule formation
2. nuclear pleomorphism
3. mitotic inded
Grade 1 (3 to 5)
Grade 2 (6 to 7)
Grade 3 (8 to 9)
How does Hormonal Status of Tumor differ in pre and post menopausal women?
ER 2/3 of post menopausal
< 1/2 of pre menopausal
What are molecular subtypes of BC?
- Luminal A
- Luminal B
- Her 2 +
- Basal like
what is Lumina A BC?
ER and PR +
Her 2 -
Ki67 low
what is luminal B BC?
two types
1. luminal B Like (her 2 -): ER +, HER 2 - and atleast one of : Ki 67 high, PR - or low
- luminal B like (Her 2 +)
ER +, Her 2 + any Ki 67 and any PR
what is Her 2 +?
Her 2 +
ER and PR -
what is Basal like BC?
TNBC
what % of symptomatic BC pts have ALN +?
50 %
what % of screen detected BC pts have ALN+?
10 to 20 %
what are RFs for IMN involvment?
- > 4 ALN +
- Inner quadrant tumors
what are regional LNs for BC?
Axillary (I to III)
Infraclavicular
IMN
supraclavicular
Which age group should undergo BC screening?
50 to 70 yrs
what are 2 views of Mammogram?
Mediolateral oblique
craniocaudal
why is mammogram less effective in young age?
Radiodense breast
when is MRI surveillance recommended?
Age 30 to 49 yrs at moderate and high risk of BC, BRCA 1 and 2 mutation and TP53
what are preventive options for high risk individual of BC?
chemoprevention
prophylactic mastectomy
what drugs are used for chemoprevention of High risk BC?
tamoxifen or Raloxifen
How does BC present?
- Breast Lump
- skin changes
- Nipple changes
- Regional disease
- metastatic disease
what are features of BC lump?
u/l, solitary, hard, irregular, non mobile and non tender
what are skin changes in BC?
thickening, redness, dimpling and/or inflammation
what is peau d’orange and why does it happen?
infiltration of tumor into the subcutaneous lymphatic channels
what are nipple changes in BC?
- loss of elasticity
- flattening or inversion of nipple
- scaly or eczema like lesion
- spontaneous discharge in pts > 50 yrs of age
what is triple assessment in BC diagnosis?
- Physical Examination
- Radiological Investigations
- Needle Biopsy
What’s advantage of core biopsy over FNAC?
provides tissue for histological examination and can differentiate between invasive and in situ carcinoma
when should metastatic work up be carried out in BC pts?
T3 and T4 disease
what is DCIS?
- True premalignant condition, 30 to 50 % of untreated DCIS will develop invasive cancer in I/L breast within 10 yr of Dxw
what’s the mammographic finding of DCIS?
Branching macrocalcifications localized to a small region of breast
what genes are often a/w DCIS
TP 53 and Her 2 amplification
what are factors a/w prognosis in DCIS?
Grade, size and distance to resection margin
Age
What’s the preferred Rx for DCIS?
WLE followed by Adjuvant RT
what margin should be achieved for WLE of DCIS?
atleast 1 mm
when is mastectomy done for DCIS?
widespread disease (>2 quadrants) or where surgical margins can not be achieved
IS LND necessary in DCIS?
No
not even SNB
what’s the role of RT in DCIS?
given after WLE, results show reduced local recurrence across all subgroups of women with DCIS
what is LCIS?
not a true premalignant condition but increased risk of BC (30 % ) lifetime risk
How does LCIS usually present?
premenopausal women; always multicentric and B/L in 1/3
WHat’s the hormonal status of LCIS?
usually ER +, HER2 - and TP53 negative
How is LCIS usually detected?
usually not palpable or detectable by mammogram
incidentally in 1% of benign breast biopsies
what’s the Rx of LCIS
observation bcoz low risk of malignant transformation (21 % over 15 years)
what type of LCIS behave like DCIS?
Pleomorphic LCIS
if at all, LCIS is to be treated Like family Hx, what surgery is done?
B/L mastectomy with/without reconstruction
risk of cancer is equal in both breasts
What’s the Rx of Early BC?
- MRM and axillary dissection
- BCS f/b RT
what structures are removed in MRM?
- entire breast
- Nipple and areola
- Axillary node dissection
What is BCT?
BCS + Adj. RT
what has NSABP-06 trial shown?
Lumpectomy + RT Vs Lumpectomy only
significant difference in Local Recurrence (14 % Vs 39%)
what’s the most important factor a/w local rec post WLE ?
margin status, should be at least 1 mm
what should be done in case of + margin post WLE?
Re-excision, if feasible, if not mastectomy
somecases RT with boost to margin
what are absolute C/Is for BCS and RT?
- Previous RT to breast / CW
- during pregnancy
- diffuse malignancies
- positive pathological margin
what are relative C/I for BCT?
- connective tissue disease
- tumor > 5 cm
- focally + margin
How many LNs should be at least resected in ALND?
10
what are S/Es of ALND?
- axillary pain and numbness
- decreased range of arm movement
- chronic lymphedema
What are different axillary LNs levels?
level I: lateral to p minor
level II: beneath p minor
level III: superomedial to p minor
when is SLNB an option instead of ALND?
Node negative BC patients
what is SLN?
1st node in regional lymphatic basin to which tumor drains
How is localization of SLN done?
injecting blue dye and radioactive colloid tracer around the tumor, into the dermis, or under the nipple
SLN are detectable as blue nodes or as radioactive nodes by hand probe
what things should be considered b4 SLNB?
- experienced surgical team
- node clinical negative
- no prev ChT or HT
What’s the current recommendation for a women with SLNB?
Axillary node clearance
What to do for T1 and T2 pts with 1 to 2 SLN + BC patients?
Z0011 study, no difference in Rx arms in terms of OS or DFS, morbidity lower in observation VS Axillary Dissection
all pts had received post op RT to preserved breast and formal nodal irradiatiion was not included
what has AMAROS trial shown?
T1-2 disease, SLN + disease
Further dissection Vs Axillary RT
No diff in OS or DFS, less lymphedema in RT arm
what’s the role of adj. RT to whole breast post BCS?
SOC, halve the risk of local rec among all subgroups of women (EBCTG, 2011)
reduced BC death at 15 years
when can omitting Adj RT be considered post BCS?
elderly women > 70 years, low risk cancers and clear margins
when is RT usually given?
post ChT
Should Anthracycline be combined with RT?
No
What are indications of SCF RT?
> 4 positive ALNs
is Axillary RT given post Axillary clearance?
N0
what are indications of Axillary RT post BCS?
AMAROS , 1 - 2 SLNs +
incomplete macroscopic excision
extensive extra nodal spread
what has MA 20 trial tested?
N+ (1 to 3) or high risk N- BC to either whole breast RT or to WBRT and nodal irradiation
Nodal RT (Axilla I to III, IMN and SCF)
Result: at 10 yr, no diff in OS, DFS improved in nodal RT 82 % vs 77 %, balanced against increased pneumonitis and lymphedema
when should IMN RT be considered? c
involved LNs
when is prone breast board used for RT ?
Large Breast
what are conventional RT field borders for BReast RT?
Medial: MIDLINE
LateraL: mid axillary line
Supr: suprasternal notch
infr: 1 cm below the breast tissue
Deep: incorporating max of 2 to 3 cm of lung
What are conventional RT field borders for SCF and axillary field?
Medial: 1 cm lateral to the midline
Lat: (SCF only): 1 cm lateral to the outer border of the 1st rib if no clips are used
Lat (SCF + axilla): to cover axillary region laterally
Supr: 3 cm above the clavicle
Infr: matched to tangential field
How are field arrangement done for SCF and Axilla?
single antr field for SCF, when axilla is added, a postr beam may be required
What are different RT dose regimens in BC?
START trial: 40 Gy/ 15#
others: 50 Gy/ 25#, 45 Gy/ 20#
FAST trial
28.5 Gy/ 5#
30 Gy/ 5#
FAST FORWARD Trial
27 Gy/ 5 #
26 Gy/ 5#
what’s the palliative RT dose for fungating tumors of Breast?
36 Gy/ 6#, once a week with weekly review
How can hotspots be reduced while planning for BC?
adding mini fields
what are OARs constraints for BC RT ?
START and FAST FORWARD trial
I/L Lung, max depth of 2 cm or V30% <17 %
Heart: max depth of 1.0 cm or
V25%<5% and V5%<30%
what things can be done if dose constraints for OAR not achieved?
MLC shielding
Breath hold technique
What is APBI?
2 fractions per day over 1 week, with RT given only to breast tissue closest to site of excised tumor
RAPID trial: increased rate of poor cosmesis with APBIo
How is Intra op RT delivered?
Single dose during surgery with electrons (6-9 MeV) or via an intrabeam device with 50 kV photons
when is ONCOtype Dx recommended by NICE ?
for ER +, LN - and Her 2 - BC
what’s the advantage of Oncotype Dx?
ChT can be avoided in low risk of recurrence pts, who previously received Chemo
what are different chemo regimens for adj BC?
1st Gen: CMF
2nd GEN: Epi-CMF
TAC
FEC f/b Taxel
AC f/b Paclitaxel
Dose Dense regimens
what’s the role of Tamoxifen in BC adjuvant setting?
useful in both pre and post menopausal women
EBCTCG : ER+ pts for 5 years, reduced annual rec by 41 % and annual mortality by 34%
which trials have compared 5 yrs vs 10 yr of tamoxifen?
ATLAST and a TTOM , further benefits
when should tamoxifen be started in adjuvant setting?
after completion of Chemo
tamoxifen is c/i, what can be done?
OFS with gosrelin
who gets most benefit from OFS?
women at greater risk of recurrence
what should be used as HT for post menopausal ladies with ER + BC?
AIs
what are s/es of tamoxifen and AI?
Tamoxifen: higher rate of gynecological and vascular symptoms
AI: arthralgia and bone #
for how long should AI be used
5 yrs
should monitor bone health
no advantage found with further extension
For how long is Trastuzumab given in adjuvant setting for Her 2 + BC ?
1 year
what’s the main S/E of Trastuzumab?
Cardiac Toxicity
when should cardiac function be monitored for Trastuzumab?
B4 starting and then every 4 months during Rx
should Anthracycline and Trastuzumab combine?
NO
Docetaxel CArboplatin and Trastuzumab is less cardiotoxic than Doxorubicin cyclophosphamide and Trastuzumab
What are LABC?
Stage IIIA (T0-3, N2, M0)
Stage IIIB (T4, N0-2, M0)
Stage IIIC (any T, N3)
How are LABC managed?
NACT or NAHT, or Her2 targeted therapy f/b BCS or mastectomy
mastectomy can be prevented in 80% of pts
When is BCT not possible?
Central Tumors
Multifocal tumors or with
Inflammatory BC
what’s other advantage of NACT except downstaging?
to assess the sensittivity of tumors to systemic therapy
pathological CR: good prognosis
pts with radiological CR: Sx can be avoided, increased local rec
what’s the usual Rx of LABC?
NACT f/b BCT and ALND + RT with /without HT (except inflammatory BC)
Mastectomy + ALND with/without RT , hormones or delayed breast reconstruction
Definitive RT to breast axilla and SCF with/without Hormones
what are features of BC during Pregnancy?
diagnosed late and often involved ALNs, larger tumors and poorly differentiated, ER/PR - and Her 2 + (30 %)
Investigations during pregnancy for BC
Mammogram (appropriate shielding of fetus)
USG breast
CxR with shielding
USG Liver
How to treat BC in 1st trimester?
Continue pregnancy and Rx with mastectomy and ALND
begin adj chemo in 2nd trimester
Taxane, trastuzumab, Adj Rt and adj HT can only be given post partum
what S/E trastuzumab cause during pregnancy?
Oligohydramnios
What’s paget disease?
1 - 4 % of BC, > 90 % are a/w underlying BC, 50% are palpable, palpable tumors are invasive cancers and 66 and 68 % have DCIS
How is pagets’s diz treated?
mastectomy and axillary staging
excision of NAC with whole breast RT
adjuvant systemic Rx as with other Breast cancers
what is inflammatory BC?
3 % of all BCs, rare but poor prognosis, rapid (< 3 months) hx of diffue, brawny indurations of skin with an erysipeloid edge
whats the receptors status in IBC?
ER/PR -
HER2 +
How is IBC managed?
NACT f/b mastectomy and ALND with ADj RT and /or HT with/without Trastuzumab
what are prognostic factors in BC?
- regional LN status: most important
- Tumor size
- Tumor grade
- Age (< 35) poor prognosis
- Hormone Receptor status
- histological type
- LVSI
- her2 status
how is histology related with prognosis?
special types of invasive BC (tubular, cribriform, mucinous, papillary, microinvasive, adenoid cystic and medullary) better prognosis then of no special type`
1st L for ER/PR +, Her 2 - post menopausal or premenopausal with OFS
Aromatase inhibitor + ribociclib (category 1)
Aromatase inhibitor + abemaciclib
Aromatase inhibitor + palbociclib
If disease progression on adjuvant endocrine therapy or relapse within 12
months of adjuvant endocrine therapy completion consider:
Fulvestrantd + CDK4/6 inhibitorb
Fulvestrant + ribociclib (category 1)
Fulvestrant + abemaciclib (category 1)
Fulvestrant + palbociclib
1st L for ER/PR +, Her 2 + post menopausal or premenopausal with OFS
- Aromatase inhibitor ± trastuzumab
- Aromatase inhibitor ± lapatinib
- Aromatase inhibitor ± lapatinib + trastuzumab
- Fulvestrant ± trastuzumab
- Tamoxifen ± trastuzumab
1st L for HR-Negative and HER2-Negative (Triple-Negative Breast Cancer; TNBC) NCCN 2025
PD-L1 CPS ≥10g regardless of germline BRCA
mutation status: Pembrolizumab + chemotherapy (albumin-bound paclitaxel,
paclitaxel, or gemcitabine and carboplatin)i (category 1, preferred)
PD-L1 CPS <10g and no germline BRCA1/2
mutation: systemic therapy
PD-L1 CPS <10g and germline BRCA1/2 mutation: * PARPi (olaparib, talazoparib) (category 1, preferred)
* Platinum (cisplatin or carboplatin) (category 1, preferred)
2nd L for HR-Negative and HER2-Negative metastatic (Triple-Negative Breast Cancer; TNBC) NCCN 2025
BRCA1/2: olaparib, niraparib
any: Sacituzumab govitecan
1st L for metastatic HR-Positive or -Negative and HER2-Positive
Pertuzumab + trastuzumab + docetaxel (category 1, preferred)
or Pertuzumab + trastuzumab + paclitaxel (preferred)
2nd L for metastatic HR-Positive or -Negative and HER2-Positive
Fam-trastuzumab deruxtecan
3rd for metastatic HR-Positive or -Negative and HER2-Positive
Tucatinib + trastuzumab + capecitabine
targeted therapies in BC
HR +, her2 -: PIK3CA: inavolisib + palbociclib + fulvestrant
alpelisib + fulvestrant
ESR 1 mutations
Elacestrant
RET fusion
selpercatinib
NTRK fusion
larotrectinib
entractenib
chemo for visceral crisis
anthracyclines
taxanes
anti metabolites
