1. Breast cancer and antieoplastic agents

Lobular v Ductal Carcinoma

Risk factors for breast cancer

Screening and Prevention

• age ___ y/o annual ____ screening

• age ___ y/o clinical encounter every 1-3 years for what 3 risk groups

Classification (4)

Classification and Treatment: ER+/PR+ Hormone Receptor Positivity BC

• The cancer cells have estrogen receptors (ER) and/or progesterone receptors (PR).

• These hormones help the cancer grow.

Treatment:

• Block estrogen or reduce estrogen levels:

  • Antiestrogens (e.g., Tamoxifen)

  • Aromatase inhibitors (e.g., Anastrozole)

  • ± CDK4/6 inhibitors (e.g., Palbociclib) to improve effectiveness

Simple idea:

• Cancer grows because of hormones, so treatment blocks hormones.

Classification and Treatment: Her2/neu (Her2) + BC

• The cancer cells make too much HER2 (Human Epidermal Growth Factor Receptor 2).

• HER2 is a growth signal receptor that causes cancer cells to grow rapidly.

Treatment:

• HER2-targeting agents or Her2 targeting agent-containing regimens:

  • Trastuzumab

  • Pertuzumab

  • Lapatinib

Simple idea:

• Cancer grows because HER2 is overactive, so treatment blocks HER2.

Classification and Treatment: Triple Negative Breast Cancer (TNBC)

The cancer is:

• ER negative

• PR negative

• HER2 negative

Therefore:

• Hormone therapy won't work.

• HER2-targeted drugs won't work.

Treatment:

• Traditional chemotherapy

• Other targeted therapies such as:

  • Sacituzumab govitecan

  • Datopotamab deruxtecan

    • ± Pembrolizumab

• Worst Prognosis of BC

Simple idea:

• Cancer lacks the common targets (ER, PR, HER2), so treatment relies on chemotherapy, immunotherapy, or newer targeted drugs.

Gene Testing for Check-point Inhibitors

• which genetic/biomarker tests can predict whether a patient will respond to immune checkpoint inhibitors

• Why do we test?

  • Checkpoint inhibitors work by taking the brakes off the immune system, allowing T-cells to attack cancer. Some tumors are much more likely to respond than others.

• PD-L1 expression testing +: Check point inhibitors

  • PD-L1 CPS

    • Combined positive score >/= 10

    • Higher PD-L1 expression → better chance of responding to checkpoint inhibitors.

• MSI-H or dMMR (VS MSI-L or pMMR): Check-point inhibitors

Gene expression assays (Oncotype DX)

• Oncotype DX®, a genetic test used in certain breast cancer patients to help decide whether chemotherapy is needed after surgery.

• Recurrence Score (RS)

• The test gives a Recurrence Score (RS) from 0 to 100

  • Low score → Low risk of recurrence

  • High score → Higher risk of recurrence

ER+ and/or PR+ Endocrine Therapy

• Aromatase inhibitors

• post menopausal woman

• pre-menopausal women with ovarian ablation/suppression

• anastazole/letrozole/exemestane

ER+ and/or PR+ Endocrine Therapy

• Antiestrogens

• selective ER modulator (or SERM): Tamoxifen

ER+ and/or PR+ Endocrine Therapy:

• SERD (Selective estrogen receptor degrader)

• Fulvestrant

• Elacestrant

• Imlunestrant

ER+ and/or PR+ Endocrine Therapy

• GnRH agonists

• only for premenopausal ovarian ablation and suppression

  • used to protect against ovarian function in premenopausal women receiving chemotherapy for fertility preservation

  • Leupolide

  • Goserelin

ER+ and/or PR+ Endocrine Therapy:

• CDK4/6 Inhibitor

• In combination with endocrine therapy (aromatase-i or tamoxifen)

• Use with GnRH inhibitor if combining with aromatase inhibitor in premenopausal women

• Abemaciclib

• Ribociclib

Definition of pre- and post-menopause

Treatment: ER+ and/or PR+ recurrent unresectable or M1 (metastatic 1)

• recurrent - cancer cam back after treatment

• unresectable - cancer cannot be removed surgically

• M1 - cancer spread to distant organs

• Treatment

  • 

Tamoxifen

• Class

• MOA

• Indication (4 subtypes of BC)

• Route of admin

• Admin schedule

• Dose

• DDI (3)

• Adverse effects (5)

  • BBW (2)

• Monitoring Plan and Consultation (6)

• Clinical pearls (2)

Fluvestrant

• Class

• Indication

• Route of admin

• Admin schedule

Raloxifene

• Class

• Indication (3)

• Route of admin

Anastrozole (Arimidex)

• Class

• MOA

• Indication (2)

• Route

• Schedule

• ADRs (3)

• DDI

• Monitoring and Plan

• Clinical pearls (2)

• Similar drugs (2)

Letrozole

• Class

• Indication (2)

• Route

• Schedule

• ADR (2)

Exemestane

• Class

• Indication (2)

• Route

• Schedule

• ADR

• DDI

Leuprolide

• CLass

• MOA

  • Males

  • Females

• Indication (3)

• Route

• Schedule

• ADR (7)

• DDI

• Monitoring and Plan (5)

• Clinical pearl

• Similar drugs (class)

Palbociclib (Ibrance)

• Class

• MOA

• Indication

• Route

• Schedule

• ADRs (2)

• DDI

Abemaciclib

• Class

• Indication

• Route

• Schedule

• ADR

• DDI

Ricbocicclib

• Class

• Indication

• Route

• ADR

• DDI

Her2+ Adjunct Chemotherapy

• Her2 Targeting Monoclonal Antibodies (3)

• Her2-Targeting TKIs (3)

Her2+ recurrent unresectable or M1 Treatment (3)

Trastuzumab (Herceptin)

• Class

• MOA

• Indication

• Admin schedules

• Dose

• ADR

  • BBW (3)

• DDI

• Monitoring Plan and Consultation (2)

• Clinical Pearls (2)

Pertuzumab (Perjeta)

• Class

• Indication

• Regimens

• ADRs

Similar drugs to Trastuzumab (Herceptin)

• Monoclonal antibody agents (-mabs) (3)

Antibody-drug conjugates

• Administration

• Agents (2)

  • Class

  • Indication

  • ADRs (3)

Tyrosine Kinase Inhibitors targeting Her2

• route of admin

• Agent (3)

  • Indication

  • ADRs (3)

Her-2 Negative Adjuvant Therapy

Therapy: TNBC (ER -, PR -, HER2-) recurrent unresectable or M1

Pembrolizumab (Keytruda)

• Class

• MOA

• Indication and Placement of Therpay

• Route of admin

• Schedule

• Dose

• ADRs

• Monitoring and Plan

Olaparib

• Class

• MOA

• Indication and Placement of therapy

• Route

• ADRs

• DDI

• Monitoring Plan

• Similar drugs (3)

Sacituzumab govitecan

Paclitaxel (Taxol)

• Class

• MOA

• Indication

• Route

• Dose

• ADR

• Monitoring Plan

• Clinical pearls

Similar drugs to paclitaxel (Taxol) (2)

Docetaxel (Taxotere)

• Class

• MOA

• Indication

• Route

• Dose

• ADR

• DDI

• Monitoring Plan

• Clinical Pearl

• Similar Drugs

Compare Docetaxel vs Paclitaxel

• Vehicle

• Extravasation

• PCV Bag Compatible?

• Hypersensitivity

• Filtration

• Premedication

• Cumulative fluids retention

• Neutropenia (dose limiting)

• Neurotoxicity

Cisplatin (Platinol)

• Class

• Route

• Admin Schedules

• DDI (3)

• Monitoring Plan

• Clinical pearls

Carboplatin (Paraplatin)

• Cross resistance with ___

• ____ better than carboplatin for certain cancers

• Dose Admin (3)

Calvert Equation for Carboplatin

Compare Cisplatin vs Carboplatin vs Oxaliplatin

• GI

• Neuro and Neuroendocrine

• Hematologic

• Nephrotoxicity

• Hypersensitivity

• Interaction with aluminum needles

• Compatibility with other solutions

Doxorubicin (Adriamycin)

• Class

• MOA

• Indication

• Admin schedules

• Dose

• ADRs

• DDIs

• Monitoring Plan

Similar drugs to doxorubicin

Cycliphosphamide

• Class

• MOA

• Indication

• ADR

• DDI

• Monitoring

Similar drugs to cyclophosphamide

Methotrexate (MTX)

• Class

• MOA

• Indication

• Dose

• ADRs

• Monitoring

• Clinical pearls

• Similar drugs

Fluorouracil (5-FU)

• Class

• MOA

• ADRs

• DDIs

• Monitoring

• Clinical pearls

HFS Grading

• Grade 1

• Grade 2

• Grade 3

Capecitabine (Xeloda)

• MOA

• Kinetics

• Interactions

• ADRs

Fertility and Birth Control

Chemoprevention (Risk Reduction Therapy)