Breast cancer

Question 1

Non-genetic risk factors for breast cancer

Answer 1

Female sex
Older age
Younger age at menarche or older age at menopause
Atypical ductal hyperplasia
LCIS
Chest radiation

Question 2

Use/effectiveness of tamoxifen chemoprevention for breast cancer

Answer 2

Reduces incidence of invasive BC but no effect on breast-cancer specific or all cause mortality
Can use in pre or post menopausal
Increased risk of endometrial CA and VTE

Question 3

Use/effectiveness of raloxifene chemoprevention for breast cancer

Answer 3

Reduced incidence of invasive breast cancer but no effect on overall mortality
Postmenopausal only
Not associated with endometrial cancer
Does have VTE risk

Question 4

Her2 positive definition

Answer 4

IHC 3+

Her2/Cep17 ratio >= 2 and average Her2 copy number >= 4

Question 5

Oncotype Dx recurrence score patient inclusion criteria and cut points

Answer 5

HR+, Her2-, LN neg breast CA
> 25 -> adjuvant chemo + endocrine tx
In women 50 or younger, >=16 benefits from chemo

Question 6

DCIS treatment

Answer 6

Breast conserving surgery with 2mm margins + radiation
ER+ give adjuvant tamoxifen/anastrozole x 5 years
Adjuvant endocrine tx reduces risk of local recurrence or contralateral disease but no established OS benefit

Question 7

Stage I-III breast CA definition of adequate surgical margins

Answer 7

No tumor present at inked margin

Question 8

Stage I-III breast CA axilla management, clinically node negative

Answer 8

SLN biopsy at surgery

Question 9

Management of positive SLN

Answer 9

Micromets only -> no ALND
1-2 positive nodes + T1-T2 + lumpectomy planning for RT + no neoadjuv therapy -> no ALND
Otherwise -> ALND

Question 10

Regional nodal radiation indication

Answer 10

After BCS or mastectomy with more than 3 involved nodes

Can consider in patients with 1-3 nodes

Question 11

Post-mastectomy RT indications

Answer 11

Tumor > 5cm
T4 disease
Positive margins
Consider for LVI

Question 12

Post-BCS radiation recommendations

Answer 12

Hypofractionated whole breast RT over 3 weeks equivalent to RT over 5-6 weeks
Women > 65 or 70 with small, node neg, ER positive tumors who are going to get endocrine therapy can omit RT

Question 13

LCIS management

Answer 13

Now classified as a benign entity
Don’t need to remove but does increase risk of cancer in both breasts
Can use tamoxifen- lowers risk of invasive BC

Question 14

Invasive tubular carcinoma management

Answer 14

Excellent prognosis

Generally treat the same as IDC but typically don’t need chemo

Question 15

Inflammatory breast cancer management

Answer 15

Neoadjuvant chemotherapy ->
Mastectomy + ALND ->
Radiation

Avoid immediate reconstruction d/t high risk of local recurrence

Question 16

Phyllodes tumor characteristics and management

Answer 16

US suggestive of fibroadenoma but tumor is big and rapidly growing
Can be benign, borderline, or malignant
Benign -> observe
Borderline/malignant -> wide excision

Question 17

Paget disease characteristics and work up

Answer 17

Nipple/areolar eczema, ulceration, bleeding, itching
Often have underlying invasive BCa
Need full-thickness skin biopsy of nipple-areolar complex + core biopsy of any breast lesion

Question 18

Paget disease management

Answer 18

Paget only (w/o invasive BCa) -> lumpectomy including nipple-areolar complex + RT or mastectomy
Paget + invasive BCa -> follow invasive disease management

Question 19

Intraductal papilloma management

Answer 19

Can present with bloody nipple discharge
Benign but can harbor areas of atypia or DCIS
Excise if evidence of atypia on biopsy

Question 20

Indications for genetic testing

Answer 20

45 or younger at BCa diagnosis
TNBC and 60 or younger
Family hx of BCa and pt <50
Male breast cancer at any age

Question 21

(Neo)adjuvant chemo regimens for HR+/Her2 neg

Answer 21

Generally don’t give chemo if tumor <0.5cm and pN0
Adjuvant chemo recommended for recurrence score > 25 (or > 16 and pt under 50 years)

Docetaxel + cyclophosphamide x4 for node neg

ddAC (doxorubicin, cyclophosphamide) x4 followed by weekly paclitaxel x12 better if 4+ nodes involved

Give chemo before giving endocrine tx

Question 22

Endocrine therapy choices

Answer 22

Premenopausal and under 35 -> ovarian suppression (OS) + AI
Premenopausal with indication for chemo -> OS + AI
Premenopausal, over 35, no chemo indication -> tamoxifen with transition to AI when post-menopausal
Postmenopausal -> AI
Men -> tamoxifen

Give ET for 5-10 years

Question 23

Management of TNBC with residual disease after neoadjuvant therapy

Answer 23

OS benefit with adjuvant capecitabine x6-8 cycles

Question 24

Management of Her2+ with residual disease after neoadjuvant therapy

Answer 24

Switch to TDM-1 to complete 1 year

Question 25

Her2+ chemo regimens and timing for early BCa

Answer 25

<2cm and node neg –> surgery then adjuvant paclitaxel + trastuzumab
>2cm and/or node+ –> neoadjuvant TCHP x6 (docetaxel, carbo, trastuzumab, pertuzumab if N+)
Always complete 1 year of Her2 directed therapy

If also ER+, add endocrine therapy during maintenance Her2 tx

Question 26

Early TNBC chemo regimens and timing

Answer 26

ddAC-T typically given neoadjuvantly for all

AC-T = doxorubicin, cyclophosphamide, paclitaxel

Question 27

Management of HR+/Her2- with residual disease after neoadjuvant therapy

Answer 27

Adjuvant endocrine therapy (which they would get anyway)

Question 28

Management of bone mets

Answer 28

Denosumab > zoledronic acid for all patients with bone mets

Increases time to skeletal-related event

Question 29

Endocrine resistant metastatic disease definition

Answer 29

Progression while receiving or within 12 months of receiving an AI

Question 30

1st line HR+/Her2- treatment for endocrine sensitive and endocrine resistant metastatic disease

Answer 30

ET sensitive- AI or fulvestrant + CDK4/6i

ET resistant- fulvestrant + CDK4/6i

Question 31

2nd line or later HR+/Her2-metastatic treatment options

Answer 31

Exemestane/fulvestrant + everolimus
Monotherapy with exemestane, fulvestrant, AI, tamoxifen, megestrol
Chemotherapy

BRCA1/2 germline mutation: Olaparib or talazoparib
PIK3CA mutation: Fulvestrant + alpelisib
Abemaciclib has single agent activity but unclear use after progression on other CDK4/6i

Question 32

1st line HR+/Her2+ metastatic treatment options

Answer 32

AI + trastuzumab +/- pertuzumab

Docetaxel + trastuzumab + pertuzumab with endocrine therapy added when chemo discontinued

Question 33

1st line HR-/Her2+ metastatic treatment

Answer 33

Docetaxel/paclitaxel + trastuzumab + pertuzumab

Generally continue chemo for 4-6 months and continue Her2 therapy until progression

Question 34

2nd line Her2+ metastatic treatment

Answer 34

Ado-trastuzumab emtansine (TDM-1)

Question 35

3rd line or later Her2+ metastatic treatment

Answer 35

Tucatinib + capecitabine + trastuzumab
Trastuzumab deruxtecan
Trastuzumab + chemo (docetaxel, paclitaxel, vinorelbine)
Trastuzumab + lapatinib
Neratinib + capecitabine
Margetuximab + chemo
Lapatinib + capecitabine

Typically continue trastuzumab beyond progression but switch what it’s given with

Tucatinib has most evidence for CNS efficacy

Question 36

1st line metastatic TNBC treatment

Answer 36

PD-L1 >= 1%: Nab-paclitaxel + atezo
Germline BRCA 1/2 mutation: olaparib or talazoparib
Single agent chemo (taxane, anthracycline, capecitabine, vinorelbine, carbo/cisplatin)

Question 37

2nd line or later metastatic TNBC treatment

Answer 37

Chemotherapy (taxane, anthracycline, capecitabine, vinorelbine, carbo/cisplatin, etc)
Sacituzumab govitecan (3rd line or later)

Question 38

Positive ipsilateral supraclavicular node staging

Answer 38

N3 , stage IIIC

Question 39

Trastuzumab deruxtecan AEs

Answer 39

Neutropenia, anemia
Nausea
Interstitial lung disease

Question 40

Chemotherapy and radiation during pregnancy

Answer 40

No chemo in 1st trimester
No her2 therapy at any time
Doxorubicin, cyclophos, and fluorouracil generally used

No RT at any time