Lec 4: Breast Cancer

Question 1

Epidemiology of breast cancer

Answer 1

• The most common cancer in women
• Second cause of death in women (after lung cancer)
• Breast cancer death rates have been decreasing since 1989… overall decline of 43% through 2020. Due to increased in awareness, and increased/ earlier screening

Question 2

Classifications of breast cancer and Stages of breast cancer

Answer 2

Classifications of breast cancer
1.) Non-invasive: Ductal Carcinoma In Situ (DCIS) - won’t go over this
2.) Invasive (~90% of breast cancer patient)
—- Non-metastatic (M0)- Stage I-III
—-Metastatic (M1)- Stage IV or recurrent
.
Stages of breast cancer
— Early Stage (Stage I and II)
— Locally Advanced (Stage III)
— Metastatic (Stage IV)

Question 3

Treatment options (general) in early stage (I and II) and locally advanced (III)? what’s the goal?…talk about the Localized treatment options ?

Answer 3

-Goal for earlier stages/ locally advance?: CURE
.
Treatment options? surgery, radiation, systemic treatment
.
Localized options (surgery and radition!)
1.) Surgery
- Lumpectomy/Breast-conserving therapy (BCT)
- Mastectomy
2.) Radiation
- Required with Lumpectomy/BCT
- Post‐mastectomy radiation only considered if LN-positive or surgical margins are close or positive

Question 4

Considerations for systemic therapy?

Answer 4

Question 5

Systemic therapy options: neoadjuvant/adjuvant (treatment algorithm)

Answer 5

Question 6

Endocrine therapy for breast cancer . . .for premeno? postmeno women?

Answer 6

Question 7

Chemotherapy for breast cancer? what are the preferred regimens and what does the letters stand for?

Answer 7

Question 8

HER2 targeted agents (monoclonal antibody) for breast cancer?

Answer 8

Question 9

Dosing and principles of trastuzumab and pertuzumab
Both: loading dose followed by maintenance

Answer 9

1.) Trastuzumab (Herceptin) IV
- 7- or 21-day cycle ( patient might be doing weekly chemo, so would make sense to give them a 7 day cycle to also admin with chemo!)
- Need to re-load if the maintenance dose missed by > 1 week
- Note: many biosimilars available (-4 letter work)
.
2.) Pertuzumab (Perjeta) IV
- 21-day cycle
- Need to re-load if it has been ≥ 6 weeks since last dose
- Hazardous agent (not a chemo.. but is it still hazardous)
.
3.) Also available as SubQ combination product: Phesgo

Question 10

Additional HER2 targeted agents: ADCs … what’s an ADC? What’s the medication name/ info?

Answer 10

Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV every 21 days x 14 cycles
- Monoclonal antibody: trastuzumab
- Chemotherapy: emtansine (MOA: microtubule inhibitor)
- Used in the adjuvant setting for patients who have residual disease following neoadjuvant therapy (used in a very specific patient population)
- no need for a loading dose!

Question 11

HH is a 45-year-old premenopausal female with Stage I HR+, HER2- breast cancer. She is status post mastectomy with the pathology report showing clean margins with
no lymph node involvement. Based on her results of the OncotypeDX test she does meet criteria for chemotherapy to be indicated. Her oncologist wants to start her on adjuvant endocrine therapy. Which agent would be an appropriate option?
A. Exemestane 25 mg PO daily for 5 years
B. Anastrozole 1 mg PO daily for 10 years
C. Tamoxifen 20 mg PO daily for 5 years
D. Tamoxifen 20 mg PO daily and letrozole 2.5 mg PO daily for 5 years

Answer 11

Question 12

What is your assessment of this patient’s therapy orders?
A. Looks good, patient is good to start treatment
B. Need to contact provider about holding or delaying chemotherapy until ANC recovery
C. Need to contact provider and recommend re-loading the pertuzumab
D. Need to contact the provider and recommend re-loading the trastuzumab-dkst

Answer 12

Question 13

Treatment options/ goals in the metastatic setting for breast cancer (general guide)

Answer 13

Goal: Palliation, prolong survival and improving quality of life
.
For HR+ patient (without symptomatic visceral metastases): generally, prefer endocrine therapy without chemotherapy
.
HR+, HER2- patients: consider CDK 4/6 inhibitors
.
Germline BRCA 1/2 mutation: consider PARP inhibitors
.
Pembrolizumab + chemo for select triple negative patients (mTNBC)

Question 14

Treatment options in the metastatic setting (Treatment Algorithm)

Answer 14

Question 15

Chemotherapy in the metastatic setting for breast cancer? Consideration? Regimens? Duration?

Answer 15

Considered the first line treatment option for:
—- ER/PR negative tumors
—- Symptomatic/visceral metastases
.
Selection of regimen:
— Single agent generally preferred for lower toxicity profile
—- Combination regimens could be considered in patient who require a rapid response
.
Duration: Until progression or unacceptable toxicity (can switch regimens)

Question 16

Immune-checkpoint inhibitor use in metastatic breast cancer

Answer 16

Pembrolizumab (Keytruda) can be considered in select mTNBC patients (added to chemotherapy- not used as monotherapy)
.
Need to test for PD-L1 expression first
— Testing for combined positive score (CPS)
— Cut off for using pembrolizumab: CPS ≥ 10 (CPS must be 10 or greater to use pembro)

Question 17

CDK 4/6 inhibitors for metastatic breast cancer

Answer 17

1.) Palbociblib (Ibrance)
2.) Ribociclib (Verzenio)
3.) Abemeciclib (Kisqali)
.
- Primary use in HR+, HER2- metastatic disease, used in combination with AIs
- Oral chemotherapeutic agents (hazardous)
- Risk of interstitial lung disease (ILD) and pneumonitis
- Substrates of CYP3A4

Question 18

PARP inhibitors for metastatic breast cancer

Answer 18

Question 19

Which of the follow is NOT an appropriate
agent for the situation stated?

A. Chemotherapy with weekly paclitaxel for a patient with metastatic HR+, HER2- breast cancer with symptomatic visceral metastases
B. Ibrance in combination with letrozole for a patient with metastatic HR+, HER2- disease without symptomatic visceral metastases
C. Olaparib for a patient with recurrence of HR+, HER2+ stage IV breast cancer with a BRCA1/2 germline mutation
D. Pembrolizumab added to chemotherapy for a patient with metastatic HR+ and HER2- breast cancer with symptomatic visceral metastases

Answer 19

D. Pembro only for triple negative