1. Epidemiology & Risk Reduction
   • Risk factors (genetic: BRCA1/2, lifestyle, hormonal).
   • Chemoprevention (tamoxifen, raloxifene, aromatase inhibitors).
   • Screening guidelines (mammography, MRI, age to start).
2. Pathophysiology & Molecular Subtypes
   • Hormone receptor–positive (ER/PR+).
   • HER2-positive.
   • Triple-negative breast cancer (TNBC).
   • Role of Ki-67, PIK3CA mutations, PD-L1 testing.
3. Treatment by Stage
   • Early-stage: surgery (lumpectomy, mastectomy, sentinel lymph node biopsy), adjuvant radiation, systemic therapy.
   • Locally advanced: neoadjuvant chemotherapy ± HER2-targeted therapy.
   • Metastatic: endocrine therapy, HER2 therapy, CDK4/6 inhibitors, immunotherapy (atezolizumab, pembrolizumab).
4. Systemic Therapy
   • Chemotherapy regimens: AC-T (doxorubicin + cyclophosphamide → paclitaxel), TC (docetaxel + cyclophosphamide).
   • Endocrine therapy: tamoxifen, aromatase inhibitors (letrozole, anastrozole, exemestane), fulvestrant.
   • HER2-targeted therapy: trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), trastuzumab deruxtecan, lapatinib, tucatinib.
   • CDK4/6 inhibitors: palbociclib, ribociclib, abemaciclib.
   • PARP inhibitors: olaparib, talazoparib (for BRCA+).
   • Immunotherapy: pembrolizumab for TNBC with PD-L1+.
5. Adverse Effects & Monitoring
   • Trastuzumab/pertuzumab → cardiotoxicity.
   • Anthracyclines → cumulative cardiotoxicity.
   • Tamoxifen → VTE, endometrial cancer risk.
   • Aromatase inhibitors → osteoporosis, arthralgias.
   • CDK4/6 inhibitors → neutropenia, diarrhea (abemaciclib).
   • PARP inhibitors → myelosuppression, fatigue.
6. Supportive Care
   • Bone health (zoledronic acid, denosumab).
   • Menopausal symptom management.
   • Fertility preservation.
   • Managing chemotherapy-induced toxicities.

BCOP Breast Cancer Study Sheet

Early-Stage / Adjuvant Breast Cancer

Locally Advanced / Neoadjuvant Breast Cancer

Metastatic / Advanced Breast Cancer

Supportive Care in Breast Cancer

Drug Treatment

• Patients with high RS should receive chemotherapy followed by endocrine therapy
• Patients with an RS < 26, low or intermediate score, endocrine therapy such as tamoxifen +/- OAS (such as goserelin) would be an appropriate option
• Patients aged ≤ 50 and RS 16-25 should receive chemotherapy
• A combination of AI and OAS, such as goserelin, is only recommended for premenopausal patients
• Docetaxel + trastuzumab + pertuzumab is recommended for metastatic breast cancer not as neoadjuvant therapy.

Prognostic Factors

Risk factors of breast cancer:

1. Age 
2. Female gender
3. History
   1. personal history
      1. Benign breast cancer
      2. Early thoracic Rth
   2. Family history: 1 first-degree relative < 50 years, or ≥ 2 at any age
4. Diet: Obesity, alcohol
5. Genetics
   1. BRCA1/2, CHECK 2, or ATM mutations
   2. Genetic syndromes or family history
6. Breast density
7. Estrogen exposure
   1. Endogenous
      1. Early age of menarche ≤ 12 years old
      2. Late age of natural menopause ≥ 55 years old
      3. Age at birth of first child ≥ 30 years old or nulliparity
      4. Early induced menopause (BSO) before 50 years old (decreases risk)
   2. Exogenous
      1. Oral Contraceptives

Drug Treatment

• Anastrazole: aromatase inhibitors are only indicated in postmenopausal women.
• Goserelin: not appropriate as a risk reduction strategy, used only for premenopausal women.
• Raloxifen: only indicated in postmenopausal women
• Tamoxifen is indicated for premenopausal women or postmenopausal women with an intolerance or contraindication to an aromatase inhibitor.
•  Trastuzumab should not be given concurrently with an anthracycline-containing regimen due to the increased risk for cardiotoxicity
•  Paclitaxel is not recommended in the adjuvant setting
•  Carboplatin is not recommended in the adjuvant setting

BREAST CANCER HORMONAL AGENTS

Mock High-Yield Breast Cancer Questions for BCOP

Treatment Duration in Early Breast Cancer

• Premenopausal: Tamoxifen ± OFS for 5 years; may extend to 10 years based on risk
• Postmenopausal: AI for 5 years, or AI for 2–3 years followed by tamoxifen to complete 5 years; extended therapy up to 10 years for high-risk
• Switching strategies: Tamoxifen → AI or AI → Tamoxifen, depending on tolerance, menopausal status

Pharmacist Monitoring & Counseling

• VTE risk: Tamoxifen — counsel on leg swelling, SOB, chest pain
• Bone health: AIs & OFS — baseline and periodic DEXA scans; recommend calcium + vitamin D, weight-bearing exercise
• Hot flashes: Avoid CYP2D6 inhibitors if on tamoxifen; use venlafaxine or gabapentin if needed
• Adherence: Stress long-term adherence for recurrence risk reduction
• Drug interactions: Especially with tamoxifen (CYP2D6), exemestane (CYP3A4)

Types of Breast Cancer

Additional Pharmacist Notes:

• Hormonal agents (tamoxifen, aromatase inhibitors) require counseling on side effects and adherence; watch for VTE and bone health.
• HER2-targeted therapy demands baseline and ongoing cardiac monitoring.
• Chemotherapy toxicity management is essential (myelosuppression, nausea, neuropathy).
• Immunotherapy requires vigilance for immune-related adverse events.
• Support patients through complex regimens and educate on symptom management.

1. “Triple-negative”

• The tumor does not express:
  • Estrogen receptor (ER)
  • Progesterone receptor (PR)
  • HER2 (human epidermal growth factor receptor 2)
• Because it lacks these targets, endocrine therapy (like tamoxifen) and HER2-targeted drugs (like trastuzumab) are ineffective.
• Treatment relies mainly on surgery ± chemotherapy, sometimes followed by radiation, depending on surgical margins and lymph node involvement.

2. “Stage IA” (AJCC 8th edition)

• T1 (tumor ≤ 2 cm)
• N0 (no regional lymph node metastasis)
• M0 (no distant metastasis)
• Also includes T1mi/T1a/T1b/T1c subcategories depending on tumor size:
  • T1a: >0.1 cm to ≤0.5 cm
  • T1b: >0.5 cm to ≤1 cm
  • T1c: >1 cm to ≤2 cm

3. Prognosis

• TNBC tends to be more aggressive biologically compared to hormone-positive cancers, but early-stage (IA) disease still has a favorable prognosis if treated appropriately.
• Five-year overall survival can exceed 90% for stage IA with optimal therapy.

4. Typical management for Stage IA TNBC

• Surgery: Lumpectomy (breast-conserving) or mastectomy.
• Adjuvant chemotherapy is generally considered for tumors >0.5 cm or with high-risk features (e.g., high grade, lymphovascular invasion), since TNBC lacks targeted options.
  • Common regimens: dose-dense AC→T, TC × 4, or weekly paclitaxel for smaller tumors.
• Radiation therapy: After lumpectomy, whole-breast irradiation is standard; after mastectomy, considered only for higher-risk features.

5. Key considerations for pharmacists

• No role for tamoxifen or aromatase inhibitors.
• HER2-directed therapy not used.
• Focus on chemotherapy toxicity management (e.g., myelosuppression, neuropathy).
• Monitor for recurrence—TNBC tends to recur earlier (first 3–5 years).

Agents Used in Chemoprevention

1. SERMs (Selective Estrogen Receptor Modulators)

• Tamoxifen
  • Only agent approved for both premenopausal and postmenopausal women.
  • Reduces risk of ER+ breast cancer by ~50%.
  • Dose: 20 mg orally daily × 5 years.
  • Side effects: hot flashes, DVT/PE, endometrial cancer risk, cataracts.
• Raloxifene
  • Approved for postmenopausal women only.
  • Equally effective as tamoxifen in invasive breast cancer prevention, but less effective in DCIS.
  • Lower risk of endometrial cancer and thromboembolic events vs tamoxifen.
  • Often chosen in postmenopausal women with osteoporosis (dual benefit).

2. Aromatase Inhibitors (AIs)

• Exemestane (25 mg daily)
• Anastrozole (1 mg daily)
• For postmenopausal high-risk women only.
• Both shown to reduce breast cancer incidence by ~50–65% in clinical trials (MAP.3, IBIS-II).
• Side effects: bone loss, arthralgias, hot flashes, cardiovascular risk.
• Need bone protection (calcium, vitamin D, bisphosphonates/denosumab if needed).

Not Used for Prevention

• Chemotherapy (anthracyclines, taxanes, etc.) → not preventive.
• Immunotherapy or HER2-targeted therapy → only for established disease.

Summary Table: Breast Cancer Chemoprevention

Key Clinical Note:

• SERMs are best for younger/premenopausal women (tamoxifen).
• AIs are best for postmenopausal high-risk women with no osteoporosis.
• Duration is usually 5 years.

Who qualifies? (High-Risk Women)

• Women with ≥1.7% 5-year risk (by Gail model) or strong family history.
• BRCA1/2 mutation carriers (though surgery is more effective for them).
• History of LCIS (lobular carcinoma in situ) or atypical hyperplasia.
• Women ≥35 years at increased lifetime risk.