Description

• Rare disease of the nipple-areola complex (NAC) typically associated with underlying in situ or invasive carcinoma
• Characterized by eczematous changes of the nipple, erythema, ulceration, crusting, bleeding, and/or itching
• Divided into three categories (1)
  • Paget disease of the nipple without ductal carcinoma in situ (DCIS)
  • Paget disease of the nipple with associated DCIS in the underlying lactiferous ducts of the NAC
  • Paget disease of the nipple with associated DCIS in the underlying lactiferous ducts of the NAC and associated DCIS or invasive breast cancer elsewhere in the breast at least 2 cm from the NAC
• System(s) affected: skin/exocrine

Epidemiology

Incidence

• 1–3% of breast cancers in females (2)
• 0.4% of invasive female breast cancer (3)
• Incidence of Paget disease of the breast has been decreasing since 1988, despite an increased incidence of breast cancer (4,5).
• Median age at diagnosis = 64 years (5)
• Extremely uncommon in males but prognosis is worse in men (6)

Prevalence
<1% of population

Etiology and Pathophysiology

• Cause is unknown, but risk factors for Paget disease are similar to those for developing breast cancer in general (see below).
• Epidermotropic theory
  • Ductal carcinoma cells migrate from underlying mammary ducts to epidermis of the nipple to become Paget cells (4,6,7).
• Transformation theory (not favored)
  • Epidermal cells of nipple/areola transform into Paget cells that can invade the basement membrane into the dermis (4,6,7).

Genetics

Risk Factors

• Same risk factors apply as for noninherited breast cancers.
• Female gender
• Age >40 years
• Previous breast cancer
• Benign breast disease (atypical ductal/lobular hyperplasia, fibroadenoma, sclerosing adenosis, intraductal papilloma)
• First-degree relative with history of breast cancer
• Caucasian
• Menarche <12 years of age
• Menopause >50 years of age
• Nulliparity or first child after age 34 years
• History of ionizing radiation exposure
• History of alcohol abuse
• Hormone replacement
• Excess weight gain

Commonly Associated Conditions

• Largest study, using surveillance, epidemiology, and end results (SEER) data representing 1,763 women with confirmed Paget disease, reports an underlying in situ or invasive breast cancer in 87% of patients, although there is often no associated breast mass or mammographic abnormality (5).
• The underlying carcinomas are multifocal/multicentric in 32–41% of patients (2)[B].