Breast cancer
# ⭐ **BREAST CANCER — COMPLETE DETAILED MEDICAL NOTE**
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# 1. **Definition**
Breast cancer is a **malignant proliferation of epithelial cells of ducts or lobules** of the breast, most commonly **invasive ductal carcinoma (IDC)**. It is the **most common cancer in women worldwide** and a leading cause of cancer mortality.
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# 2. **Pathophysiology (Stepwise)**
1. **Genetic mutations** → BRCA1/BRCA2, TP53, PTEN, HER2 amplification.
2. **Hormonal influence** → Lifetime estrogen exposure stimulates proliferation of breast epithelium.
3. **DNA damage accumulation** → loss of apoptosis, uncontrolled proliferation.
4. **Tumor microenvironment changes** → angiogenesis, immune evasion.
5. **Local invasion** → ducts → stroma → lymphatics.
6. **Metastasis** → axillary nodes → bone, lung, liver, brain.
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# 3. **Etiology / Risk Factors**
### **A. High-risk**
* BRCA1/BRCA2 mutation
* Strong family history
* Previous chest radiation (Hodgkin therapy)
* Atypical ductal hyperplasia, LCIS
### **B. Moderate/General**
* Early menarche, late menopause
* Nulliparity or late first pregnancy
* Hormone replacement therapy
* Obesity, sedentary lifestyle
* Alcohol, smoking
* Dense breasts
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# 4. **Clinical Features**
### **Breast symptoms**
* Painless **hard irregular mass** (upper outer quadrant common)
* Nipple retraction
* Nipple discharge (bloody/serous)
* Skin changes: **peau d’orange**, ulceration, dimpling
* Axillary lump
### **Advanced**
* Bone pain, dyspnea, jaundice, neurological deficits (metastasis).
### **Special types**
* **Inflammatory breast cancer:** rapid onset redness, edema, peau d’orange; aggressive.
* **Paget disease of nipple:** eczematous nipple lesion.
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# 5. **Investigations / Diagnosis**
### **Initial**
1. **Clinical breast exam**
2. **Imaging**
* **<30 yrs:** Ultrasound
* **>30 yrs:** Mammography (BI-RADS scoring)
* MRI breast in high-risk (BRCA, dense breasts)
### **Definitive**
3. **Core needle biopsy** (gold standard)
* Histology type
* **Receptor status:** ER, PR, HER2
* Ki-67 proliferation index
### **Staging**
4. **TNM staging**
5. **Metastatic workup**
* CT chest/abdomen/pelvis
* Bone scan / PET-CT
### **Genetic testing**
* BRCA1, BRCA2, TP53 (Li-Fraumeni), PTEN (Cowden), PALB2.
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# 6. **Differential Diagnoses**
* Fibroadenoma
* Fibrocystic disease
* Fat necrosis
* Phyllodes tumor
* Mastitis / breast abscess
* Papilloma
* Duct ectasia
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# 7. **Stepwise Management**
Management depends on **stage**, **receptor status**, **age**, **menopausal status**.
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## **A. Localized Early-Stage Cancer (I–II)**
### 1. **Surgery**
* **Breast-conserving surgery (lumpectomy)** + **Radiation**
* **Modified radical mastectomy** (if large tumor or patient preference)
### 2. **Sentinel lymph node biopsy**
### 3. **Radiation therapy**
After lumpectomy: mandatory
After mastectomy: if T3/T4 or >4 LN positive
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## **B. Systemic Therapy (Based on Receptor Status)**
### 1. **Hormone-Receptor Positive (ER/PR +)**
→ **Endocrine therapy**
#### **a. Premenopausal**
* **Tamoxifen** 20 mg/day × 5–10 years
* * Ovarian suppression (GnRH analogs)
#### **b. Postmenopausal**
* **Aromatase inhibitors (AIs)**
* Letrozole 2.5 mg/day
* Anastrozole 1 mg/day
* Exemestane 25 mg/day
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### 2. **HER2-Positive Tumors**
→ **Anti-HER2 therapy**
* **Trastuzumab** IV every 3 weeks × 1 year
* **Pertuzumab** may be added
* Avoid with **LVEF <55%**
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### 3. **Triple-Negative Breast Cancer (TNBC)**
→ No ER/PR/HER2
* **Chemotherapy is primary therapy**
* Anthracycline + taxane
* Platinum agents in BRCA mutation
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### 4. **Chemotherapy (Standard Regimens)**
* **AC → T regimen**:
* Doxorubicin (Adriamycin) 60 mg/m²
* Cyclophosphamide 600 mg/m²
* Followed by Paclitaxel 80 mg/m² weekly
* **CMF regimen**: Cyclophosphamide + Methotrexate + 5-FU
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## **C. Metastatic Breast Cancer (Stage IV)**
* **HR+** → Endocrine therapy + CDK4/6 inhibitor (Palbociclib)
* **HER2+** → Trastuzumab + pertuzumab + docetaxel
* **TNBC** → Immunotherapy (Pembrolizumab) + chemo
* Bone mets → **Zoledronic acid** or **Denosumab**
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# 8. **Drug Details (Mechanism, Dose, AE, Contra, Monitoring, Counselling)**
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## ⭐ **Tamoxifen**
**Indication:** ER+ breast cancer (pre/postmenopausal).
**MOA:** SERM — antagonist in breast, agonist in bone & uterus.
**Dose:** 20 mg orally daily.
**Adverse effects:** Hot flashes, DVT/PE, endometrial carcinoma, cataracts.
**Contra:** Hx of DVT/PE, pregnancy.
**Interactions:** Warfarin increases bleeding.
**Monitoring:** Annual pelvic exam, coagulation risk, LFTs.
**Counselling:** Report vaginal bleeding, leg swelling.
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## ⭐ **Aromatase inhibitors (Letrozole/Anastrozole/Exemestane)**
**Indication:** Postmenopausal ER+ cancer.
**MOA:** Block conversion of androgens → estrogen.
**Dose:** Letrozole 2.5 mg/day; Anastrozole 1 mg/day.
**AE:** Osteoporosis, arthralgia, hot flashes.
**Contra:** Premenopausal (unless ovarian suppression).
**Monitoring:** DEXA scans, bone health.
**Counselling:** Calcium/Vitamin D, exercise.
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## ⭐ **Trastuzumab**
**Indication:** HER2+ breast cancer.
**MOA:** Monoclonal antibody against HER2 receptor.
**Dose:** IV every 3 weeks × 1 year.
**AE:** **Cardiotoxicity** (reversible), infusion reactions.
**Contra:** LVEF <55%
**Monitoring:** Baseline and 3-monthly echocardiography.
**Counselling:** Report dyspnea, fatigue.
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## ⭐ **Doxorubicin (Anthracycline)**
**MOA:** Intercalates DNA, inhibits topoisomerase II, generates free radicals.
**Dose:** 60 mg/m².
**AE:** **Cardiotoxicity (dose-dependent)**, myelosuppression, alopecia, mucositis, red urine.
**Monitoring:** LVEF, CBC, LFTs.
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## ⭐ **Paclitaxel (Taxane)**
**MOA:** Stabilizes microtubules → inhibits mitosis.
**AE:** Peripheral neuropathy, myelosuppression, hypersensitivity.
**Monitoring:** CBC, neuropathy assessment.
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## ⭐ **GnRH analogs (Leuprolide)**
**Indication:** Ovarian suppression in premenopausal ER+ cancer.
**AE:** Hot flashes, osteoporosis.
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## ⭐ **CDK4/6 inhibitors (Palbociclib)**
**MOA:** Blocks cell cycle progression via CDK4/6 inhibition.
**AE:** Neutropenia.
**Monitoring:** CBC weekly initially.
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## ⭐ **Bisphosphonates (Zoledronic acid)**
**Indication:** Bone metastasis.
**AE:** Osteonecrosis of jaw.
**Counselling:** Dental exam before therapy.
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# 9. **Non-Pharmacologic Measures**
* Weight control
* Exercise
* Avoid alcohol
* Breastfeeding reduces risk
* Screening mammography from age 40–50 onward
* Genetic counselling for BRCA families
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# 10. **Prevention**
### **Primary**
* Prophylactic mastectomy for BRCA
* Prophylactic oophorectomy
* Tamoxifen prophylaxis in high-risk women
### **Secondary (Screening)**
* Mammography every 1–2 years >40 yrs
* MRI for BRCA mutation carriers
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# 11. **Staging Overview**
* **Stage I:** Localized small tumor
* **Stage II:** Local tumor + limited lymph nodes
* **Stage III:** Locally advanced
* **Stage IV:** Distant metastasis
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