PHRM 542 Breast Cancer Curative Intent Treatment

What is the goal of stage 0/I/II breast cancer?

CURATIVE INTENT

Describe surgical options used for stage 0/I/II breast cancer

Surgery can cure almost all in situ cases

Breast-conserving surgery (BCS)

Total mastectomy

Describe the use of radiation therapy in stage 0/I/II breast cancer

Required with BCS

Post-mastectomy radiation considered if lymph nodes are positive or surgical margins are close or positive

What stages are considered early stage breast cancer?

Stage I and II

What systemic adjuvant treatments are used for early stage breast cancer?

Endocrine therapy

Chemotherapy

Biologics (HER2 targeted therapy)

What stage is considered early stage locally advanced breast cancer?

Stage III

What systemic adjuvant treatments are used for locally advanced breast cancer?

Endocrine therapy

Chemotherapy

Neoadjuvant chemotherapy

Dual-HER2 targeted therapy

What are the strongest prognostic factors for predicting future recurrence or death from breast cancer?

Patient age, comorbidity, tumor size, tumor grade, number of involved LNs, possibility HER2 tumor status

What is the general treatment for HR positive HER2 positive breast cancer?

Chemotherapy + trastuzumab + endocrine therapy

What is the general treatment for HR positive HER2 negative breast cancer?

Endocrine therapy +/- chemotherapy

What is the general treatment for HR negative HER2 positive breast cancer?

Chemotherapy + trastuzumab

What is the general treatment for HR negative HER2 negative breast cancer?

Chemotherapy

What are curative intent adjuvant endocrine therapy choices?

Tamoxifen

Ovarian ablation or suppression

Aromatase inhibitors

What are curative intent adjuvant chemotherapy choices?

Anthracycline-containing regimens

Taxane-containing regimens

What are curative intent adjuvant biological therapies?

Trastuzumab

Pertuzumab

What is a curative intent adjuvant immunotherapy?

Pembrolizumab

What are the two examples of adjuvant endocrine therapy for HR positive breast cancer in premenopausal women?

1. Tamoxifen for 5 years

2. Tamoxifen or AI + ovarian suppression for 5 years

When should an additional 5 years of tamoxifen be considered?

If the patient is still pre-menopausal at year 5 consider an additional 5 years of therapy for a total of 10

What are examples of ovarian suppression?

1. Bilateral Salpingo-oopherctomy

2. Lutenizing Hormone Receptor Agonists

What are the four examples of adjuvant endocrine therapy for HR positive breast cancer in postmenopausal women?

1. AI (preferred) for 5-10 years

2. Tamoxifen for 2-3 years followed by AI to complete 5 years or for an additional 5 years

3. AI for 2-3 years followed by tamoxifen to complete 5 years

4. Women with C/I to AI or who decline AI = tamoxifen x 5-10 years

What is the benefit of adjuvant endocrine therapy in HR positive breast cancer in pre and post menopausal women?

NO survival benefit

The benefit shown has been decreased risk of recurrence

What are the core components of any adjuvant treatment regimen for breast cancer?

ANTHRACYCLINES AND TAXANES

This is the standard of care!!!

What are the benefits of adjuvant therapy in breast cancer?

Reduction in odds of recurrence

Reduction in the odds of death

What are examples of adjuvant chemotherapy for node negative breast cancer?

Anthracycline-containing regimen +/- concurrent or sequential taxane

Non-anthracycline-containing regimen

What is an example of adjuvant chemotherapy for node positive breast cancer?

Anthracycline-containing regimen WITH concurrent or sequential taxane

What are the four mechanisms of trastuzumab?

Blocks cleavage

Blocks dimerization

Endocytosis leading to HER2 degradation

Activation of antibody-dependent cell-mediated cytotoxicity (tumor-cell lysis)

When is trastuzumab indicated?

Adjuvant/neoadjuvant, HER2 positive

Metastatic, HER2 positive

What are black box warnings of trastuzumab?

CARDIOTOXICITY

Infusion reactions

Pregnancy

How should trastuzumab be monitored?

LVEF at baseline and every 12 weeks during treatment

S/sx of infusion or pulmonary toxicity

When is pertuzumab indicated?

Adjuvant/neoadjuvant, HER2 positive; in combination with trastuzumab; Add when T > 2 cm OR N1 or greater

Metastatic HER2 positive

What are black box warnings of pertuzumab?

CARDIOTOXICITY

Pregnancy

How should pertuzumab be monitored?

LVEF at baseline and every 12 weeks during treatment

Monitor for infusion reaction, diarrhea, and hypersensitivity

What should anti-HER2 agents not be used concomitantly with?

NEVER give anti-HER2 agents with anthracyclines (increased cardiotoxicity risk)

What biological agent should never be used as monotherapy for HER2+ breast cancer?

Pertuzumab

Define neoadjuvant chemotherapy

Systemic treatment PRIOR to definitive surgical therapy

What are the benefits of giving chemotherapy +/- HER2?

Downstage the tumor

Higher rates of clinical response BUT not shown to improve disease free or overall survival

May be able to qualify for breast conservation

Describe triple negative breast cancer (TNBC)

Lack expression of the ER/PR and HER2

Tends to be more aggressive

Describe the treatment of TNBC

NO HER2 or endocrine therapy

Chemotherapy and/or checkpoint inhibitors

What is the indication for olaparib (PARP inhibitor)?

Early, high-risk, HER2-negative, germline BRCA-mutated for adjuvant therapy

What are example regimens of olaparib for BRCA1 or 2 breast cancer?

Standard chemotherapy (adjuvant or neoadjuvant) THEN 1 year of olaparib

Long term maintenance

What is the MOA of PARP inhibitors?

Blocks PARP enzymes that normally repair single-strand DNA breaks, leading to damage accumulation and cell death

Lethal for cancer cells with BRCA mutations as now there is no back up method for DNA repair to fix downstream double-strand breaks