What is the treatment for Paget's disease?

Treatment of Paget's Disease

For Paget's disease of bone, the recommended treatment is alendronate 40 mg once daily for six months, which effectively normalizes serum alkaline phosphatase in approximately 85% of patients. 1

Paget's Disease of Bone

Diagnosis

• Typically diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase
• Symptomatic patients present with bone pain, fractures, arthritis, and features of compression neuropathy 2
• Diagnosis is confirmed by typical radiological features on plain films
• Radionuclide bone scan may be used to assess the extent of disease

Treatment Algorithm

1. First-line treatment: Bisphosphonate therapy

   • Alendronate 40 mg once daily for six months 1
   • Zoledronic acid is the most effective agent, with a single infusion leading to sustained reduction in bone pain and markers of bone turnover 2

2. Administration instructions:

   • Take alendronate at least 30 minutes before the first food, beverage, or medication of the day
   • Take with plain water only (6-8 oz)
   • Remain upright for at least 30 minutes after taking the medication
   • Do not take at bedtime or before arising for the day 1

3. Supplementation:

   • Calcium supplementation if dietary intake is inadequate
   • Vitamin D supplementation, especially for patients over 70 years, nursing home-bound, or chronically ill 1

4. Re-treatment considerations:

   • Re-treatment may be considered following a six-month post-treatment evaluation period
   • Indicated for patients who have relapsed based on increases in serum alkaline phosphatase
   • Also consider for those who failed to normalize their serum alkaline phosphatase 1

Important Considerations

• Bisphosphonates should be reserved for symptomatic patients, as treatment has been associated with increased fracture rates in asymptomatic patients 2
• Response to treatment is defined as either normalization of serum alkaline phosphatase or decrease from baseline greater than or equal to 60% 1
• Alendronate is effective regardless of age, gender, race, prior use of other bisphosphonates, or baseline alkaline phosphatase levels 1

Paget's Disease of the Breast

Paget's disease of the breast is a rare manifestation of breast cancer characterized by neoplastic cells in the epidermis of the nipple-areolar complex, presenting with eczema, bleeding, ulceration, and itching of the nipple 3.

Diagnosis

• Clinical presentation: Nipple or areolar eczema, ulceration, bleeding, itching 3
• Diagnostic workup:
  • Clinical breast exam
  • Diagnostic bilateral mammogram, ultrasound as necessary
  • Full-thickness skin biopsy of involved nipple-areolar complex
  • Consider MRI to assess extent of disease 3

Treatment Options

1. Mastectomy with or without axillary staging:

   • Traditional standard treatment
   • Always an option with any manifestation of Paget's disease 3
   • Appropriate for extensive disease

2. Breast-conserving surgery with radiation therapy:

   • Excision of nipple-areolar complex with negative margins
   • Whole-breast radiation with boost to nipple-areolar complex site
   • Equivalent outcomes to mastectomy in appropriate candidates 4

3. Axillary management:

   • Sentinel lymph node biopsy should be performed in cases with invasive component 5
   • Consider axillary staging for patients with DCIS undergoing mastectomy 3

4. Adjuvant therapy:

   • For Paget's disease without associated cancer or with DCIS: Consider tamoxifen 20 mg daily for 5 years 3
   • For associated invasive cancer: Appropriate systemic adjuvant therapy based on tumor characteristics 3

Treatment Algorithm Based on Presentation

1. Paget's disease alone (no underlying cancer):

   • Excision of nipple-areolar complex with whole-breast radiation, or
   • Mastectomy with consideration of axillary staging 3

2. Paget's disease with DCIS:

   • Mastectomy with consideration of axillary staging, or
   • Excision of breast tumor and nipple-areolar complex with whole-breast radiation 3

3. Paget's disease with invasive cancer:

   • Mastectomy with axillary staging, or
   • Excision of breast tumor and nipple-areolar complex with axillary staging and whole-breast radiation 3

Despite the availability of breast-conserving options with equivalent outcomes, studies show that only about 18% of eligible patients undergo central lumpectomy, with most still receiving mastectomy 4. Patients should be informed that breast conservation is an oncologically safe option with appropriate case selection 5.