Breast Cancer

Question 1

Epidemiology

• Most ___ malignancy in women in US
• 2nd most common cause of cancer related ___ in women
• Lifetime risk of developing breast cancer is 1 in __ women (risk increases with age)

Answer 1

• common
• death
• 8

Question 2

T or F: increased HRT could contribute to the decreased in mortality based on results from the WHI study.

Answer 2

FALSE
- decreased HRT

decreased mortality is believed to be due to better treatments for both early and advanced breast cancer as well as screening

Question 3

Risk Factors

More than 60% of patients will not have any risk factors
- increasing age
- Family history - relatives with disease increases risk
- Radiation
- ___ exposure endogenous - Early menarche late menopause
- Exogenous ___ OC/HRT
- alcohol - decreases hepatic ___ of estrogen
- Prior breast ___ with proliferative histology
- ___ or age > 30 years old before first birth
- Elevated BMI/Diet

Answer 3

• estrogen
• estrogen
• metabolism
• biopsies
• nulliparity

Question 4

Genetics

Only ~ 5-10% of breast cancers are familial

Tumor Suppressor Genes
BRCA-1
- increased risk of ___ cancer (up to 40% lifetime risk) and ___ cancers (up to 60%)
- High prevalence of variants in Ashkenazi Jews

BRCA-2
- Greater risk for breast cancer (~50%), lower risk for ovarian (~20%)
- Greater incidence in male breast cancer

Answer 4

• ovarian
• breast

Question 5

Types: Invasive Breast Cancer

Invasive carcinoma -invaded beyond the basement membrane of the duct or lobule
1. Invasive ___ carcinoma (IDC) – Most common accounting for 70% of all breast cancers
2. Invasive ___ carcinoma (ILC) – Second most common type ~ 15% of breast cancers

Answer 5

• ductal
• lobular

Question 6

Types: Non-Invasive Breast Cancer

Ductal carcinoma in situ (DCIS) –
- Normal cells have undergone pre-malignant genetic transformation
- Typically seen as microcalcifications on a ___

Lobular carcinoma in situ (LCIS)
- Has not invaded beyond the ___ basement membrane
- Usually, an incidental finding on biopsy specimen obtained because of symptoms or mammographic findings consistent with benign lesions

Answer 6

• mammogram
• lobule

Question 7

Types of Breast Cancer

Inflammatory:
- ___ form of breast cancer with rapid onset and poor prognosis
- The onset is typically days and weeks
- peau d’ ___
- delayed in diagnosis because most often thought of as cellulitis, so typically treated with multiple antibiotics before the diagnosis is made

Answer 7

• aggressive
• orange

Question 8

FISH Testing

Can test for HER2 status in 2 different ways:
1. Immunohistochemistry (IHC): Detects ___ overexpression (1+, 2+, 3+)
2. Fluorescence In-Situ Hybridization (FISH): Detects gene ___ (if gene: chromosome copies are ≥ 2 considered positive)

Answer 8

• protein
• amplification

Question 9

Oncotype DX

• Genetic test for expression of 21 genes which gives a recurrence score
• Can determine the likelihood that the breast cancer will ___ and whether the patient is likely to benefit from ___

Multi-gene assay validated for use in:
- ___ diagnosed breast cancer
- Stage __ or __
- Lymph node negative and positive (1-3 nodes)
- ER positive
- HER2 negative

Answer 9

• return
• chemo
• newly
• I, II

Question 10

Oncotype DX: TAILORx

Low risk (< 26) = ___ therapy only

High risk (≥ 26) = ___ and
___ therapy
- the medium score group did not benefit from chemo (score of 16 to 25)
- women < ___ years of age and score of 16-25 did have a benefit from chemo

Demonstrates ~ 85% of people can be spared chemo

Answer 10

• hormone
• chemo, hormone
• 50

Question 11

Natural History of Breast Cancer

T or F: Breast cancer can metastasize anywhere

Answer 11

T
- Malignant progression involves early changes in proliferation by systemic hormones
- Sites of metastasis: Bone, liver, lungs, brain, distant lymph nodes and/or skin

Question 12

Adjuvant: ___ surgery
Neoadjuvant: ___ surgery

Answer 12

• after
• before

Question 13

Stages I, II, and IIIA-C
- Goal is ___
- Lumpectomy + XRT
- Mastectomy + XRT

stage II and IIIA patients may have
___ chemo
- Most women will receive adjuvant therapy

Stage IV
- Treatment is ___
- primarily consists of chemo, hormonal therapy, +/- biologics, +/- immunotherapy
– radiation may be used to palliate symptoms
– Surgery only used for ___ relief

Answer 13

• cure
• neoadjuvant
• palliative
• symptomatic

Question 14

T or F: radiation is an example of a neoadjuvant therapy

Answer 14

FALSE:
can only use XRT after surgery

Question 15

Neoadjuvant therapy

Stage I, IIA, IIB, III disease

Goal: cure
- For patients with ___ tumors (> __ cm)

Benefits of neoadjuvant chemotherapy:
» 1. Allows less extensive ___
» 2. Allows you to see ___ to chemo while the tumor is still intact

Answer 15

• larger
• 1
• surgery
• response

Question 16

Systemic Adjuvant Therapy

Answer 16

Question 17

Adjuvant Hormonal Therapy

Surgical ablation:
– Oopherectomy: Removes the largest source of ___

Selective Estrogen Receptor Modulators (SERMs) - ___ (Nolvadex)
- Anti-estrogenic effects in breast but estrogenic properties in
other tissues (bones, lipids)
- Reduces risk of developing contralateral breast cancer
* Dosage: 20 mg daily
* Major toxicities – ___ , endometrial cancer and DVT (uncommon)

Answer 17

• estrogen
• tamoxifen
• hot flashes

Question 18

Adjuvant Hormonal Therapy

LHRH Analogs
- ___ (Lupron): Monthly or Q 3 months
- ___ (Zoladex implant): Monthly or Q 3 months
- Flare: Initially causes increased release of ___ and ___
- Long-term, sustained exposure inhibits ___ production by the ovaries
- Estrogen and progesterone levels fall to ___ status after 2 - 4 weeks

Answer 18

• leuprolide
• goserelin
• FDH, LH
• estrogen
• post-menopausal

Question 19

Aromatase Inhibitors (AI)

• Use only in ___ patients
• Will need to use ___ suppression if in a premenopausal woman
• Fewer adverse effects: No DVT/endometrial cancer, no protective effect on ___ (like tamoxifen)
• Osteoporosis, hot flashes, muscle aches, and pains

anastrozole, letrozole, exemestane
- used for ___ years and then reevaluated

Answer 19

• postmenopausal
• ovarian
• bone
• 5 years

Question 20

T or F: Durations longer than 3 to 6 months of adjuvant chemotherapy improve survival

Answer 20

FALSE
- do not appear to improve survival

Question 21

Most common chemotherapeutic agents: (8)

Answer 21

• doxorubicin
• epirubicin
• cyclophosphamide
• methotrexate
• fluorouracil
• carboplatin
• paclitaxel
• docetaxel

Question 22

Chemotherapy Regimens

Standard chemotherapy consists of __ - __ cycles given every __ - __weeks

Answer 22

• 4-6
• 3-4

Question 23

Adjuvant Chemotherapy Regimens

HER 2 negative disease (2)

Dose Dense ___→ ___ (NCCN preferred)
- ___ and ___
- repeat every ___ days
- must give ___
- followed by ___

___ (NCCN preferred)
- ___ and ___

Answer 23

• AC, Paclitaxel
• doxorubicin, cyclophosphamide
• 14
• growth factors
• paclitaxel
• TC
• docetaxel, cyclophosphamide

Question 24

Dose Dense Anthracyclines

CALBG trial
- Evaluated dose density and sequential versus combination chemotherapy questions
- Group 4 = (every __ weeks plus ___ ) = Concurrent doxorubicin and cyclophosphamide x 4 followed by paclitaxel x 4
- Sequential therapy was found to be less ___
- Patients got same amount of chemo but in ___ time (hence, dose dense)

Answer 24

• 2, filgrastim
• toxic
• less

Question 25

If cardiac problems, can consider ___ chemo regimen to avoid anthracyclines

Answer 25

TC - docetaxel, cyclophosphamide

Question 26

# Adjuvant HER2 (+) Regimens 3 regimens 1. A**PT** 2. TCH 3. TCH + ___

Answer 26

1. APT = paclitaxel and trastuzumab 2. TCH = docetaxel, carboplatin, trastuzumab 3. TCH + pertuzumab

Question 27

# Duration of Therapy HERA (Herceptin Adjuvant Trial) - standard of care is to complete ___ year of adjuvant trastuzumab therapy - Now with pertuzumab, will complete ___ year of combined trastuzumab and pertuzumab

Answer 27

- one - one

Question 28

# Residual Disease Therapy Katherine Trial: HER2 (+), with residual disease found on pathology after surgery - Received ≥ 6 cycles of ___ (TDM-1) or trastuzumab IV every 3 weeks x 14 cycles - ___ = Risk of recurrence or death was 50% lower compared to trastuzumab alone - New standard of care - If no residual disease, continue trastuzumab +/- pertuzumab x total of ___ year

Answer 28

- ado-trastuzumab emtansine - TDM-1 - 1

Question 29

# TNBC: Triple Negative Breast Cancer: Standard of Care Immunotherapy now is incorporated into chemo regimen for TNBC - improved OS with addition of ___ to standard chemotherapy - should be added into chemo regimen and continued for __

Answer 29

- pembrolizumab - 1

Question 30

# Adjuvant Chemotherapy Regimens Triple negative disease (1) ___ + chemo - ___ + ___ + Pembrolizumab - Repeat every 21 days x 4, then followed by: - ___ + ___ + Pembrolizumab - Repeat every 21 days x 4, then followed by: - Pembrolizumab to complete __ year of therapy

Answer 30

pembrolizumab - paclitaxel, carboplatin - doxorubicin, cyclophosphamide - 1

Question 31

# Metastatic Disease Goal of therapy is ___ - Median survival is ~ 3 years - Bone and soft tissue metastases tend to have a better prognosis and respond to ___ therapy - Symptomatic disease: ___ * ___(+) tumors tend to be more indolent

Answer 31

- palliation - hormonal - chemo - ER/PR

Question 32

# How to Decide What to Give Hormonal Therapy - ER/PR+ - ___ disease free survival - prior response to therapy - ___ only disease Chemo - ER/PR - disease - ___ disease free interval - ___ progressing disease - Disease ___ to hormonal therapy

Answer 32

- long - bone - short - rapidly - refractive

Question 33

HER2+ metastatic disease: First line ___ + ___ + ___

Answer 33

trastuzumab pertuzumab docetaxel

Question 34

___ is now considered 2nd line after failure of trastuzumab / pertuzumab and a taxane - also now an option in those with HER2 ___ disease

Answer 34

Fam-trastuzumab deruxtecan - low

Question 35

# Triple Negative Breast Cancer (TNBC) ___ agents have shown benefit (2)

Answer 35

platinum - carboplatin - cisplatin

Question 36

# Triple Negative Breast Cancer (TNBC) ___ + chemotherapy is better than chemo alone in patients with a combined positive score of ≥ 10 - if no positivity, the platinum-based chemo is preferred | combined positive score: number of PD-L1 staining cells

Answer 36

pembrolizumab

Question 37

# Hormonal Therapy: Metastatic Common to use sequential endocrine therapies in the metastatic setting - If a patient responds to one endocrine therapy, it is ___ they will respond to another agent - As the response time shortens with each line of therapy, it is likely that the patient will no longer respond to endocrine therapy and then ___ should be initiated

Answer 37

- likely - chemo

Question 38

# Hormonal Therapy: Metastatic 1st Line - ___ inhibitor + ___ inhibitor (abemaciclib, palbociclib, or ribociclib) 2nd Line - ___ + CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) if not used before - ___ + endocrine therapy (exemestane, Fulvestrant, or tamoxifen)

Answer 38

- aromatase, CDK4/6 - fulvestrant, everolimus

Question 39

# Breast Cancer Prevention Trials Three agents have been studied in the preventative setting

Answer 39

- tamoxifen - raloxifene - exemestane

Question 40

# Prevention Tamoxifen and Raloxifene are effective - both drugs reduce breast cancer by 50% - Raloxifene did not reduce the risk of ___ or ___ like tamoxifen

Answer 40

- LCIS, DCIS