Radiation Oncology/Breast/Pagets

Paget's Disease of the Breast

Overview

• Historical description:

"[the nipple and areola have the] appearance of a florid intensely red raw surface; very finely granular, as if the whole thickness of the epidermis were removed; like the surface of very acute diffuse eczema … (with) cancer of the mammary gland (following) within at the most two years and usually within one year …"

Sir James Paget
"On disease of the mammary areola preceding cancer of the mammary gland."
St. Bartholomew's Hosp Rep 1874; 10: 87-9.

• Clinical presentation of crusting, mild scaling, itching, and redness of the nipple skin. These can progress to more destructive stage, with burning, eczema, and nipple discharge, followed by ulceration and bleeding
• Association with underlying breast cancer reported in 1874 by Sir James Paget
  • >95% of patients with Paget's Disease have underlying breast cancer (~10% DCIS, ~90% invasive)
  • However, <5% of all breast cancer patients present with Paget's Disease symptoms
• Underlying breast cancer
  • If palpable or mammographic mass, >90% will be invasive carcinoma, and >50% may have LN+
  • If non-palpable, 60-80% will be DCIS
• Work-Up
  • Bilateral breast examination
  • Mammogram
  • Biopsy

Pathophysiology

• Malignant epithelial (Paget) cells infiltrate and proliferate in the epidermis, causing thickening of the nipple and the areolar skin
• This is believed to be from retrograde extension of underlying intraductal carcinoma into the overlying epidermis through mammary duct epithelium
• Derived from luminal lactiferous ductal epithelium of the breast tissue

Staging

• Stage 0 - no associated DCIS or invasive disease
• Stage I - associated with DCIS underneath the nipple
• Stage II - associated with extensive DCIS
• Stage III - associated with invasive ductal carcinoma

Treatment Overview

• Treatment strategy is typically dependent on the underlying malignancy (DCIS vs. IDC)
• Mastectomy was the historical treatment, but breast conservation therapy appears to be increasing
• Conservative surgery alone appears inadequate, with recurrence rates 20-40%
• BCS + lymph node assessment and adjuvant RT is likely a reasonable strategy for appropriately selected patients

• US Multi-Institutional (1980-2000)
  • 2003 PMID 12712465 -- "Conservative management of Paget disease of the breast with radiotherapy: 10- and 15-year results." (Marshall JK, Cancer. 2003 May 1;97(9):2142-9.)
    • Retrospective. 7 institutions, 36 patients without palpable mass or mammographic density. Complete/partial nipple-areolar complex excision in 94%, 100% whole breast RT 50 Gy, 97% boost to remaining nipple/tumor bed (median total dose 61.5 Gy). Median F/U 9.4 years
    • Outcome: LR 16% (50% DCIS, 50% IDC); 5-year LC 91%, 10-year LC 83%, 15-year LC 76%; DFS 93%, 90%, 90%
    • Conclusion: Excellent rate of LC, DFS and OS at 10 and 15 years following BCS and RT
  • 1997 PMID 9305706 -- "The conservative management of Paget's disease of the breast with radiotherapy." (Pierce LJ, Cancer. 1997 Sep 15;80(6):1065-72.)

• EORTC 10873; 2001 (1987-1998) PMID 11169928 -- "Breast-conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients." (Bijker N, Cancer. 2001 Feb 1;91(3):472-7.)
  • Registry study. 61 patients. 97% presented without associated palpable mass, 93% had underlying DCIS, 7% had no associated disease. Treatment was complete excision of nipple-areolar complex, SM-, followed by whole breast RT 50/25. Median F/U 6.4 years
  • Outcome: Absolute LR 7% (2% DCIS and 5% IDC); 5-year LR 5%
  • Conclusion: BCT is a feasible alternative for patients with Paget's and limited extent DCIS