Breast Cancer (Riley)

table of tx for reference

Recommended treatment plan for ER/PR+, HER2+ breast cancer: neoadjuvant (2)

1. TCHP

2. ddACTHP - trastuzumab ± pertuzumab to complete in 1 year

Recommended treatment plan for ER/PR-, HER2- breast cancer: neoadjuvant (2)

1. ddACT ± carboplatin
2. Taxol/carboplatin/pembrolizumab followed by AC/pembrolizumab

Recommended treatment plan for ER/PR-, HER2- breast cancer: adjuvant

ddACT ± carboplatin

Recommended treatment plan for ER/PR+, HER2- breast cancer: neoadjuvant/adjuvant (2)

1. Docetaxel + cyclophosphamide

2. ddACT

Recommended treatment plan for ER/PR-, HER2+ breast cancer: neoadjuvant (2)

1. TCHP

2. ddACTHP - trastuzumab ± pertuzumab to complete in 1 year

Recommended treatment plan for ER/PR-, HER2+ breast cancer: adjuvant

Paclitaxel + trastuzumab

Recommended treatment plan for ER/PR+, HER2+ breast cancer: adjuvant

Paclitaxel + trastuzumab

Recommended treatment for breast cancer with BRCA1/2 mutation

Olaparib

Recommended treatment for breast cancer with PIK3CA mutation (3)

1. Capivasertib

2. Alpelisib

3. Inavolisib

Recommended treatment for breast cancer with MSI-H/dMMR

Pembrolizumab

Recommended treatment for breast cancer with CDK4/6 over-expression (2)

1. Abemaciclib

2. Ribociclib

What is the most common dose-limiting side effect with the combination of trastuzumab + pertuzumab?

diarrhea

What drugs are specifically used in ER+/PR+ breast cancer?

endocrine therapy, should be initiated AFTER chemotherapy (adjuvant)

Unique adverse effects for Tamoxifen (SERM) (3)

1. Hot flashes

2. DVT and PE risk

3. Increased risk of endometrial cancer

Unique adverse effects for aromatase inhibitors (ex. anastrozole, letrozole) (3)

1. Hot flashes

2. Arthralgias

3. Osteopenia and osteoporosisis

Why are GNRH inhibitors used with aromatase inhibitors in premenopausal patients and not (usually) in post-menopausal patients? (2)

1. In premenopausal women, aromatase inhibitors (AIs) must be combined with a GnRH agonist to suppress ovarian function (estrogen production), rendering the patient functionally postmenopausal so the AI can effectively lower systemic estrogen levels.

2. After menopause, the ovaries no longer produce significant estrogen. Therefore, AIs are effective as monotherapy in postmenopausal women, with no need for additional ovarian suppression

What is the likely dose limiting adverse effect for the breast cancer drug ribociclib used for CDK4/6 over-expression?

neutropenia

How is the mucositis associated with everolimus mitigated for breast cancer treatment?

swishing with dexamethasone oral solution

What screening modalities are available for breast cancer?

• Brest Self Examination (BSE) 

  • generally not recommended d/t false positives 

• Clnical Breast Exam (CBE) 

  • not uniformly recommended 

• Mammography 

  • Starting at age 40 yearly (American cancer society) or q2 years (USPTF) 

Breast MRI → adjunct to mammogram in high-risk patients (ex: BRCA mutation carrier)

What are the risk factors for developing breast cancer?

Age 

Family history of breast cancer 

Endogenous Estrogen Exposure 

Exogenous Estrogen Exposure 

Benign Breast Disease/Dense Breast Tissue on mammogram 

Radiation exposure to the breast or chest 

Obesity and BMI 

Physical activity 

Alcohol intake 

Which mutations are common in breast cancer?

HER2 (20-30%)

Which molecular tests are routinely obtained for breast cancer?

Hormone Receptor Status (ER/PR)	HER2	TNBC
-Used to predict response to endocrine therapy  - Presence of estrogen receptors (ER) or progesterone receptors (PR) occur in 60-75% of breast cancers  - Positive test common in post-menopausal women → higher response to endocrine therapy and longer disease free survival	- overexpression of HER2 associated with transmission of cancer growth signals  - occurs in 20-30% of breast cancers  - higher mortality rates	15% of cancers

What is the difference in meaning between neoadjuvant treatment vs adjuvant treatment?

Neoadjuvant treatment - preoperative, treatment given BEFORE surgery to shrink tumor

Adjuvant - postoperative, treatment given AFTER surgery to prevent recurrence

 in early breast cancer, pembrolizumab is only indicated in ________

triple negative

How does the mechanism of action of tamoxifen differ from that of the aromatase inhibitors?

Aromatase Inhibitor	MOA
Anastrozole	Decreases estrogen biosynthesis by selective inhibition of aromatase (estrogen synthase)
Exemestane	Irreversible steroidal aromatase inactivator, decreases estrogen biosynthesis in peripheral tissues
Letrozole	Decreases estrogen biosynthesis by selective competitive inhibition of aromotase in peripheral tissues (estrogen synthetase)  Inhibition of aromotase reduced conversion of adrenal androgens (testosterone + androtenedione) to estradiol/estrone

What are the typical side effects of tamoxifen, the aromatase inhibitors, and the GNRH inhbitors?

Tamoxifen	BBW:  → increased risk of uterine malignancies  → thromboembolic events: DVT + Stroke & PE
Aromatase inhibitors	Hot flashes
GNRH inhibitors	Tumor flare (temporary worsening of sx)

How is the mucositis associated with everolimus mitigated?

Stomatitis - risk for mouth sores,

SWISH Trial: Preventative Dexamethasone rinse