Breast cancer

Breast cancer is a malignant tumor arising from the epithelial tissues of the breast and is the most common cancer among women worldwide. Although the exact etiology remains unknown, several genetic, hormonal, reproductive, and environmental factors have been associated with an increased risk of developing the disease. Early detection through screening and prompt treatment significantly improve survival and treatment outcomes.

Management of breast cancer requires a multidisciplinary approach involving breast surgeons, clinical oncologists, radiologists, pathologists, radiation oncologists, and specialized nursing staff.

Epidemiology

Breast cancer is the most common malignancy affecting women globally and is a leading cause of cancer-related mortality. The incidence increases with age and is influenced by reproductive, genetic, hormonal, and lifestyle factors.

Both early-stage and advanced-stage disease occur, although outcomes are significantly better when the disease is detected before regional or distant spread.

Risk factors

Risk factors associated with breast cancer include:

• Increasing age.

• Nulliparity.

• Not breastfeeding.

• First pregnancy after 35 years of age.

• Previous radiation exposure.

• Family history of breast cancer.

• Smoking.

• Alcohol consumption.

Pathophysiology

Breast cancer develops from malignant transformation of epithelial cells within the breast ducts or lobules. Progressive genetic alterations result in uncontrolled cellular proliferation, local invasion, lymphatic spread, and distant metastasis.

Common sites of metastasis include:

• Bone.

• Lung.

• Liver.

• Brain.

Tumor biology is influenced by hormone receptor status and HER2 expression, which guide treatment selection and prognosis.

Clinical presentation

Breast cancer may present as a breast lump, breast skin changes, nipple abnormalities, regional lymphadenopathy, or symptoms related to metastatic disease.

Some patients are diagnosed through screening before symptoms develop.

Symptoms

Local disease

• Breast lump.

• Breast swelling.

• Breast discomfort or pain.

• Nipple retraction.

• Nipple abnormalities.

• Breast ulceration.

• Changes in breast shape or size.

Regional disease

• Axillary swelling.

• Symptoms related to regional lymph node involvement.

Metastatic disease

• Persistent cough.

• Bone pain.

• Pathological fractures.

• Neurological symptoms.

• Symptoms related to liver involvement.

• Generalized weight loss.

Clinical signs

• Solitary hard breast lump or mass.

• Skin dimpling.

• Skin thickening.

• Breast ulceration.

• Nipple retraction.

• Axillary lymphadenopathy.

• Supraclavicular lymphadenopathy.

• Fixation to chest wall muscles.

• Fungating breast lesion in advanced disease.

• Signs of metastatic disease.

Differential diagnosis

Conditions that may mimic breast cancer include:

• Fibroadenoma.

• Fibrocystic breast disease.

• Breast cyst.

• Mastitis.

• Breast abscess.

• Fat necrosis.

• Duct ectasia.

• Intraductal papilloma.

• Phyllodes tumor.

• Tuberculosis of the breast.

• Metastatic lesions involving the breast.

Diagnostic criteria

Breast cancer should be suspected in patients presenting with:

• A hard breast lump or mass.

• Nipple retraction.

• Breast skin changes.

• Breast ulceration.

• Axillary lymphadenopathy.

• Fixed breast mass.

• Suspicious findings on breast imaging.

Diagnosis is confirmed through histopathological examination of breast tissue.

Screening

Breast cancer screening includes:

Breast self-examination (BSE)

Women should be educated on regular breast self-examination and encouraged to report suspicious findings promptly.

Clinical breast examination (CBE)

Clinical examination by a trained healthcare provider.

Breast imaging

• Mammography.

• Breast ultrasonography.

• Breast MRI where indicated.

All patients with clinically suspicious lesions should undergo appropriate imaging as part of early detection and diagnosis.

Investigations

Laboratory investigations

• Full blood count (FBC).

• Liver function tests (LFTs).

• Renal function tests (RFTs).

• Urea.

• Creatinine.

Cardiac assessment

• Echocardiography (ECHO).

• Multigated acquisition scan (MUGA).

These are required for baseline ejection fraction assessment and treatment monitoring.

Imaging investigations

• Bilateral mammography.

• Breast ultrasound where indicated.

• Chest X-ray (CXR).

• Abdominal and pelvic ultrasound.

• Bone scan.

• CT scan where indicated.

• PET/CT where indicated.

• Breast MRI in selected patients with equivocal mammographic or ultrasound findings.

Histopathological investigations

• Core needle biopsy (preferred).

• Ultrasound-guided core needle biopsy.

• Stereotactic-guided core needle biopsy.

• Open biopsy where indicated.

Immunohistochemistry (IHC)

Assessment of:

• Estrogen receptor (ER).

• Progesterone receptor (PR).

• Human epidermal growth factor receptor 2 (HER2).

Molecular confirmation

For equivocal HER2 results:

• Fluorescence in situ hybridization (FISH).

• Chromogenic in situ hybridization (CISH).

Diagnostic staging

Breast cancer should be staged using:

• TNM staging system.

Management

Management may include:

• Surgery.

• Chemotherapy.

• Radiotherapy.

• Endocrine therapy.

• Targeted therapy.

Optimal treatment requires multidisciplinary evaluation involving a breast surgeon and clinical oncologist.

Non-pharmacological treatment

Surgical management

Breast-conserving surgery (BCS)

Options include:

• Lumpectomy.

• Quadrantectomy.

Breast-conserving surgery should only be performed when postoperative radiotherapy is available.

Modified radical mastectomy

Modified radical mastectomy is the preferred surgical option when access to radiotherapy is limited.

Toilet mastectomy

May be considered in selected advanced cases for symptom control.

Axillary staging

All surgical procedures should include:

• Axillary lymph node dissection.

• Level I and II nodal clearance.

• More than 10 lymph nodes should be sampled where feasible.

Radiotherapy

Radiotherapy is strongly indicated in:

• Patients following breast-conserving surgery.

• T3–T4 tumors.

• Positive surgical margins.

• Four or more positive lymph nodes.

• Palliation of:

  • Fungating tumors.

  • Bleeding tumors.

  • Bone metastases.

  • Brain metastases.

Radical radiotherapy dose

• 50 Gy in 25 fractions over 5 weeks.

Or

• Hypofractionated radiotherapy:

  • 40.05 Gy in 15 fractions.

Palliative radiotherapy dose

• 30 Gy in 10 fractions over 2 weeks.

Pharmacological treatment

General principles

Chemotherapy may be used as:

• Neoadjuvant therapy.

• Adjuvant therapy.

• Palliative therapy.

Patients with tumors ≥ T3 should receive neoadjuvant chemotherapy before surgery.

HER2-negative disease

Regimen 1: Dose-dense AC followed by weekly paclitaxel

Doxorubicin

• 60 mg/m² intravenously over 30 minutes on Day 1.

AND

Cyclophosphamide

• 600 mg/m² intravenously over 1 hour on Day 1.

Repeat every 14 days for 4 cycles.

Followed by:

Paclitaxel

• 80 mg/m² intravenously over 1 hour weekly for 12 weeks.

Regimen 2: AC followed by 3-weekly taxane

Doxorubicin

• 60 mg/m² intravenously over 30 minutes on Day 1.

PLUS

Cyclophosphamide

• 600 mg/m² intravenously over 1 hour on Day 1.

Repeat every 21 days for 4 cycles.

Followed by either:

Paclitaxel

• 175 mg/m² intravenously over 3 hours on Day 1 every 21 days for 4 cycles.

OR

Docetaxel

• 100 mg/m² intravenously over 3 hours on Day 1 every 21 days for 4 cycles.

Regimen 3: TAC regimen

Docetaxel

• 75 mg/m² intravenously over 3 hours on Day 1.

AND

Doxorubicin

• 50 mg/m² intravenously over 30 minutes on Day 1.

AND

Cyclophosphamide

• 500 mg/m² intravenously over 1 hour on Day 1.

Repeat every 21 days for 6 cycles.

HER2-positive disease

Trastuzumab-containing regimen

Doxorubicin

• 60 mg/m² intravenously over 30 minutes on Day 1.

AND

Cyclophosphamide

• 600 mg/m² intravenously over 1 hour on Day 1.

Repeat every 21 days for 4 cycles.

Followed by:

Paclitaxel

• 80 mg/m² intravenously over 1 hour weekly for 12 weeks.

AND

Trastuzumab

• 4 mg/kg intravenously with the first dose of paclitaxel.

Then:

Trastuzumab

• 2 mg/kg intravenously weekly to complete one year of treatment.

Alternative trastuzumab schedule

Following completion of paclitaxel:

Trastuzumab

• 6 mg/kg intravenously every 21 days.

Continue until one year of trastuzumab treatment is completed.

Other chemotherapy regimens

• CAF (Cyclophosphamide, Adriamycin, 5-Fluorouracil).

• CEF (Cyclophosphamide, Epirubicin, 5-Fluorouracil).

• CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil).

CMF may be considered in elderly patients (>65 years) with poor cardiac function.

Metastatic breast cancer (Stage IV)

Combination regimens include:

• CAF.

• CEF.

• Gemcitabine plus paclitaxel.

• Trastuzumab plus paclitaxel/carboplatin.

• Trastuzumab plus paclitaxel.

• Trastuzumab plus docetaxel.

• Trastuzumab plus capecitabine.

Single-agent therapy options include:

• Trastuzumab.

• Taxane.

• Capecitabine.

• Gemcitabine.

Endocrine therapy

Premenopausal ER/PR-positive disease

Tamoxifen

• 20 mg orally once daily for 5 years.

Postmenopausal ER/PR-positive disease

Anastrozole

• 1 mg orally once daily for 5 years.

OR

Tamoxifen

• 20 mg orally once daily for 2 years.

Followed by:

Anastrozole

• 1 mg orally once daily for 3 years.

Monitoring during treatment

• Full blood count (FBC) before each cycle.

• Renal function tests before each cycle.

• Liver function tests before each cycle.

• Cardiac monitoring at baseline, 3 months, 6 months, and 9 months.

• Myeloid growth factor support for chemotherapy cycles.

Management according to underlying disease subtype

HER2-negative disease

• Anthracycline-based chemotherapy.

• Taxane-containing chemotherapy regimens.

HER2-positive disease

• Chemotherapy combined with trastuzumab.

ER/PR-positive disease

• Endocrine therapy according to menopausal status.

Metastatic disease

• Palliative chemotherapy.

• Endocrine therapy where appropriate.

• Targeted therapy where indicated.

• Palliative radiotherapy for symptom control.

Referral

All patients with suspected or confirmed breast cancer should be referred urgently to a specialized oncology center for definitive evaluation and management.

Referral should include:

• Histopathological diagnosis.

• Imaging results.

• Staging information.

• Receptor status (ER, PR, HER2).

Complications

• Local recurrence.

• Regional lymph node recurrence.

• Bone metastases.

• Lung metastases.

• Liver metastases.

• Brain metastases.

• Pathological fractures.

• Malignant pleural effusion.

• Treatment-related complications.

• Death.

Prognosis

Prognosis depends on:

• Stage at diagnosis.

• Tumor size.

• Lymph node involvement.

• Histological grade.

• ER, PR, and HER2 status.

• Response to treatment.

Early-stage disease has a favorable prognosis, whereas advanced metastatic disease is associated with lower survival despite modern therapies.

Prevention

• Breast cancer awareness and education.

• Breast self-examination.

• Regular clinical breast examination.

• Mammographic screening where available.

• Reduction of modifiable risk factors such as smoking and alcohol use.

• Early evaluation of suspicious breast symptoms.

• Timely referral of patients with suspicious breast lesions.

Follow-up

Patients should undergo regular follow-up for:

• Detection of recurrence.

• Monitoring of treatment toxicity.

• Assessment of treatment response.

• Surveillance for metastatic disease.

• Long-term monitoring of cardiac function in patients receiving trastuzumab or anthracycline-based therapy.