Paget's Disease of the Nipple

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Paget's Disease of the Nipple is an uncommon breast disease and traditionally was treated with mastectomy.

See approach to nipple discharge from the NCCN here and here, and read the reviews on  Paget's from Harris Textbook and E-Medicine. There may be a role for conservative surgery followed by radiation as the studies below suggest:

Cancer 2001 Feb 1;91(3):472-477

Breast-conserving therapy for paget disease of the nipple.

Bijker N, Rutgers EJ, Duchateau L, Peterse JL, Julien JP, Cataliotti L

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

BACKGROUND: The purpose of the current study was to assess the outcome of breast-conserving therapy by means of a cone excision and radiotherapy in patients with Paget disease of the nipple without associated invasive breast carcinoma. METHODS: Between 1987 and 1998, 61 eligible patients were registered in the European Organization for Research and Treatment of Cancer Study 10873. The majority of patients (97%) presented without an associated palpable mass. At histologic examination, the majority (93%%) of patients had an underlying ductal carcinoma in situ (DCIS); in the remaining 7%, only Paget disease was found. Treatment was comprised of a complete excision of the nipple-areolar complex including the underlying breast tissue with tumor free margins, followed by external irradiation to the whole breast (50 gray in 25 fractions). The primary endpoint was local recurrence. RESULTS: At a median follow-up of 6.4 years, 4 of the 61 patients developed a recurrence in the treated breast (1 patient with DCIS and 3 patients with invasive disease). One patient with an invasive local recurrence died of disseminated breast carcinoma. The 5-year local recurrence rate was 5.2% (95% confidence interval, 1.8-14.1%). CONCLUSIONS: Breast-conserving therapy is a feasible alternative for patients with Paget disease and a limited extent of underlying DCIS. To achieve good local control, treatment should be comprised of a complete excision of the nipple-areolar complex including the underlying disease, followed by irradiation to the whole breast.

Cancer 1997 Sep 15;80(6):1065-72

The conservative management of Paget's disease of the breast with radiotherapy.

Pierce LJ, Haffty BG, Solin LJ, McCormick B, Vicini FA, Wazer DE, Recht A, Strawderman M, Lichter AS

Department of Radiation Oncology, University of Michigan School of Medicine

The purpose of this study was to evaluate the feasibility of breast-conserving therapy involving limited surgery and definitive radiotherapy as a treatment for Paget's disease, and to determine the disease free and overall survival associated with this approach. The authors retrospectively reviewed the charts of all patients treated during the period 1980-1994 for Paget's disease of the breast who did not present with a palpable mass or mammographic density. Through a collaborative review, 30 cases were identified. A biopsy confirming the presence of typical Paget's cells was performed on all patients. All patients received external beam radiotherapy to the breast, with a median dose of 50 gray (Gy). Ninety-seven percent received a boost to the remaining nipple or tumor bed, with a median dose to the tumor bed of 61.5 Gy. Three patients (10%) developed a recurrence in the breast as the only site of first failure, and 2 additional patients (7%) experienced failure in the breast as a component of first failure. The median time to local failure was 69 months. The 5- and 8-year actuarial estimates of local failure as the only site of first failure were 9% (95% confidence interval [CI], 0-20%) and 16% (95% CI, 0-31%), respectively. Of the 5 patients with local failures, 3 were among 22 patients (14%) who underwent complete resection of the nipple or nipple-areola complex, compared with 2 failures among 6 patients (33%) after partial resection (P = 0.29). There were no failures among 2 patients who had a biopsy only. Four of 5 local failures were salvaged by mastectomy, and 3 of these patients were free of disease after a median follow-up of 52 months. The 5- and 8-year estimates of disease free survival for the overall series were both 95% (95% CI, 87-100%); cause specific overall survival was 100% at 8 years. CONCLUSIONS: Breast-conserving therapy involving complete resection of the nipple-areola complex followed by definitive radiotherapy is a viable alternative to mastectomy in the treatment of Paget's disease. High rates of disease free and cause specific survival, in addition to adequate local control, justify consideration of a conservative approach.

Radiother Oncol 1990 Apr;17(4):305-9

Breast conserving treatment of Paget's disease.

Bulens P, Vanuytsel L, Rijnders A, van der Schueren E

Department of Radiotherapy, University Hospital, St. Rafael, Leuven, Belgium.

Between 1971 and 1984, 13 patients with histologically proven Paget's disease were treated conservatively with radiotherapy only. The disease was clinically confined to the nipple or surrounding skin, without signs of an underlying tumor. With a mean follow-up of 58.6 months (ranging between 15 and 118 months), and a median follow up of 52 months, no recurrences locally or at distance were seen. Therefore in these selected cases a mastectomy could be avoided. The results with this breast conserving management suggest a place for radiotherapy in the treatment of Paget's disease limited to the nipple.

J Gynecol Obstet Biol Reprod (Paris) 1987;16(8):1069-73

Paget's disease of the nipple without any associated mammary tumor clinically or radiologically detectable. Apropos of 51 cases treated at the Curie Institute.

Campana F, Vielh P, Fourquet A, Schlienger P, Jullien D, Durand JC, Salmon R, Vilcoq JR

Departement de Radiotherapie, Institut Curie, Paris.

Between 1960 and 1984, 51 patients with Paget's disease of the nipple, with no concomitant palpable or radiological breast tumour, were treated at the Institut Curie. The diagnosis was made in all cases through a simple biopsy of the nipple and/or the areola. All slides were reviewed for the present study. 20/51 patients were treated conservatively, with external radiotherapy alone (17/20 pts), or limited surgery and radiotherapy (3/20 pts). The mean age was 54 years (range 40 to 80). The median follow-up was 7.5 years. No patients died of breast disease. Three local recurrences occurred and were treated by mastectomy. All were located in the nipple or areola and were Paget's disease without intraduct or invasive carcinoma. The actuarial probability of living 4.5 years free of disease when the breast is preserved with a good cosmetic result is 81%. 31/51 patients underwent mastectomy; 30 a modified mastectomy, 1 a simple mastectomy. The mean age was 66 years (range 55 to 90). Associated intraduct carcinoma was found in 30/31 microscopic examinations. No axillary node invasion was found after dissection of the axilla. In the group treated by surgery, the median follow-up was 5 years. No patient died of breast disease. No chest wall recurrence occurred. The 5 years disease-free survival rate was 87%. This retrospective non randomized study of 51 patients treated for Paget's disease of the nipple suggests that radiotherapy is a valuable alternative to mastectomy.

Lancet 1989 Sep 16;2(8664):664-6

Radiotherapy for Paget's disease of the nipple: a conservative alternative.

Stockdale AD, Brierley JD, White WF, Folkes A, Rostom AY

Regional Centre for Radiotherapy and Oncology, St Luke's Hospital, Guildford, Surrey.

The case records of 28 patients with Paget's disease of the nipple treated by radio-therapy alone were reviewed retrospectively. 16 of 19 patients who had no palpable underlying tumour and who were mammographically normal at the time of original treatment remain free of disease with a median follow-up of 5 years 3 months. In this selected group, radical radiotherapy with small fields localised to the involved skin is an effective alternative to mastectomy.

S Afr Med J 1988 Jan 23;73(2):95-7

Paget's disease of the breast.

du Toit RS, van Rensburg PS, Goedhals L

Department of Surgery, University of the Orange Free State, Bloemfontein.

Twenty patients with histologically proven Paget's disease of the breast are reviewed. They represent an incidence of 1.06% of all breast carcinomas seen over a 12-year period in the Bloemfontein academic hospitals. All cases had ductal carcinoma. Clinically, 20% presented with a mass only, 20% with nipple disease only and 60% with both lesions. More patients with a mass compared with patients with only nipple disease had positive axillary lymph nodes--68.7% v. 25%. Cumulative 5-year survival rates showed a 100% survival rate for patients with only nipple disease, and an 83% survival rate for stage I and II disease. All the patients with stage III and IV disease died within the 4-year follow-up period. Nipple (skin) involvement per se did not worsen the prognosis of patients presenting with both a mass and nipple disease. The main predictors of prognosis were tumour size and lymph node involvement. It is suggested that patients presenting with nipple involvement only and/or small T1 lesions close to the nipple could be treated with wide local excision and axillary dissection in discontinuity followed by radiotherapy to the rest of the breast.

Tumori 1976 Sep-Oct;62(5):529-35

Analysis of 100 cases of Paget's disease of the breast.

Salvadori B, Fariselli G, Saccozzi R

Of 100 cases of Paget's disease of the breast admitted to the National Career Institute of Milan from 1940 to 1974, 91 were statistically evaluated. They were divided in two groups according to presence or absence of a palpable nodule. The results of surgical treatment in terms of 5 and 10 year survival rates were 59 and 44%, respectively, with a median survival of 9 years. For the two separate subgroups, those with a palpable nodule were 38 and 22% for 5 and 10 years, respectively, while those without a palpable nodule were 92 and 82% for 5 and 10 years, respectively. For the two groups the median survival was 3.6 and 16.4 years, respectively. The extent of surgery should be dependent on the presence of absence of palpable nodules under the nipple. For the two groups (with and without) extended radical mastectomy and the Patey-Dawson mastectomy are recommended.

Cancer 1981 Aug 1;48(3):825-9

Pathogenesis and treatment of Paget's disease of the breast.

Paone JF, Baker RR

Fifty cases of Paget's disease of the breast treated surgically at The Johns Hopkins Hospital during the past 30 years were studied. Nineteen patients had Paget's disease confined to the nipple and 31 had an associated palpable tumor. An underlying intraductal or infiltrating duct carcinoma of the breast was present in each case. In six cases, the underlying tumor was 2 cm or more from the nipple with no apparent anatomic connection to the Paget lesion, and one case was encountered in whom intradermal Paget's disease develop in the area of a congenitally absent nipple. These findings support the theory of an intradermal origin for the Paget cell. Survival rates of patients with Paget's disease and a palpable breast mass were similar to those of patients with infiltrating duct carcinoma, the presence of axillary node metastases being the most important prognostic factor. Actuarial five- and ten-year survival rates were 22% and 9.9% for patients with positive nodes. The modified radical mastectomy is recommended as primary therapy for this group of patients. In contrast, none of the patients with Paget's disease of the nipple and no evidence of a palpable breast mass developed recurrent carcinoma. A total mastectomy without an axillary node dissection is the treatment of choice in this type of patient.

Cancer 1984 Aug 1;54(3):545-51

Paget's disease of the nipple. Alternative management in cases without or with minimal extent of underlying breast carcinoma.

Lagios MD, Westdahl PR, Rose MR, Concannon S

Six cases of Paget's disease of the nipple without clinical or mammographic evidence of a breast mass are described, two without underlying carcinoma of duct origin, and four with very limited duct carcinoma in situ of the most distal lactiferous ducts. Ultrastructural and immunohistochemical studies on these cases demonstrate that Paget cells arise in situ and invalidate the prevalent "epidermotropic" theory of histogenesis. Paget's disease of the nipple is considered to be an independent in situ carcinoma and part of the general phenomenon of multicentricity in breast cancer. A therapeutic option of conservative surgical intervention and follow-up is described for five of these select patients, all of whom are presently without evidence of disease with an average follow-up of 50 months (range, 30-69 months).

J Am Coll Surg 1998 Aug;187(2):171-7

Paget's disease of the breast: a 33-year experience.

Kollmorgen DR, Varanasi JS, Edge SB, Carson WE

Division of Surgical Oncology, Roswell Park Cancer Institute, State University of New York at Buffalo, USA.

Paget's disease (PD) of the breast is an uncommon condition traditionally treated with mastectomy. To assess the natural history and treatment options in PD we have reviewed the experience at the Roswell Park Cancer Institute (RPCI). The medical records of patients treated for PD at RPCI between 1963 and 1996 were reviewed. RESULTS: Eighty patients were treated in the period reviewed. The median follow up was 61 months. Sixty-eight of 80 patients had nipple changes consistent with PD including 30 who had an associated breast mass (group 1), and 38 who had no associated mass (group 2). Of the 68 patients with clinical PD, 58 (85%) were treated with mastectomy while the remainder were treated with some form of breast conserving therapy. Breast cancer (BC) was found in 56 of 68 patients (82%) with clinical PD, including 28 of 30 patients (93%) in group 1 and 28 of 38 patients (74%) in group 2. Breast cancer was centrally located (within 2 cm of the areolar margin) in 61% of patients, including 71% in group 1 and 50% in group 2. Of the 28 patients with an associated BC in group 1, 21 (75%) had invasive cancer, 6 (21%) had ductal carcinoma in situ (DCIS), and 16 (57%) had pathologic axillary nodes. Of the 28 patients with an associated BC in group 2, 10 (36%) had invasive cancer, 18 (64%) had DCIS, and 6 (21%) had positive axillary nodes. The median survival was significantly shorter for group 1 (42 months) than for group 2 (126 months; p = 0.007). CONCLUSION: Most patients with PD have an associated BC (82%) that was centrally located (61%). In those patients without an associated mass, a significant number (26% in this series) may not have an underlying BC and may be overtreated with mastectomy. On the other hand, a significant number of patients with PD and no associated breast mass will be found to have a peripherally located tumor (29% in this series). These non-central BC masses could potentially be missed by a wide local excision that includes the areolar complex.

J Surg Oncol 1977;9(1):93-8

Paget's disease of the breast.

Freund H, Maydovnik M, Laufer N, Durst AL

Twenty-nine histologically verified cases of Paget's disease of the breast treated at the Hadassah University Hospital in the years 1949-1972 were followed up and analyzed. Dividing this material into two groups according to the presence or absence of a palpable breast tumor revealed significant difference in behavior and survival. Patients with a breast mass (34%) had a 50% axillary lymph node involvement and behaved as with any other ordinary breast cancer, with a 5-year survival rate of 40% and a 10-year survival rate of 33%. Patients with no palpable breast mass (66%) had only a 10.5% lymph node involvement, the 5-year survival rate being 94% and the 10-year survival rate being 91%. Delay in diagnosis seems to play no significant factor in survival rates and outcome. We believe radical mastectomy to be the treatment of choice in all cases of Paget's disease of the breast.

Zhonghua Zhong Liu Za Zhi 1989 May;11(3):216-8

Paget's disease of the nipple

Zhang BN

Cancer Hospital, Chinese Academy of Medical Sciences, Beijing.

Fifty-five female patients with Paget's disease of the nipple treated in our Hospital from 1958 to 1987 are reported. It comprised 1.1% of all the breast carcinomas. The lesions was on the left side in 27 and on the right side in 28. The average age was 48 years. The primary lesion was in breast ducts and then invaded the nipple, areola superficially and deeper breast tissue. Dermal manifestation of Paget's disease is easily confused with chronic dermopathy. In this series, four patients (7.2%) did not have the typical symptoms so pathologic or cytologic examination was relied upon for correct diagnosis. Thirty-one patients were treated by radical mastectomy giving a 3-year disease-free rate of 70.9%. It seems that radical mastectomy is more superior to the other surgical procedures. The 3-year recurrent rate was 38% for patients with Paget's disease of the nipple coexisting with breast carcinoma, but no recurrence was found in patients with simple Paget's disease of the nipple. The 3-year survival rate was 46.4% in patients with axillary lymph node metastasis, 85.2% in patients without, 54.3% in patients with palpable masses in the breast and 85.0% in patients without. Paget's disease of the nipple coexisting with breast carcinoma, axillary lymph node metastasis, palpable breast masses has poor prognosis.

Ann Surg Oncol 1997 Jun;4(4):287-92

Underlying pathology in mammary Paget's disease.

Yim JH, Wick MR, Philpott GW, Norton JA, Doherty GM

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

BACKGROUND: Management of patients with mammary Paget's disease is controversial; recent recommendations range from primary radiotherapy to modified radical mastectomy. This review correlates associated breast findings with disease stage and outcome to help guide evaluation and treatment. METHODS: Retrospective review of clinical, mammographic and pathologic data from 38 women with mammary Paget's disease treated between 1979 and 1995 was performed. Mastectomies were performed on all but two patients with the entire breast and lymph nodes evaluated for histopathologic evidence of carcinoma. RESULTS: Underlying carcinoma (ductal carcinoma in situ and/or invasive ductal cancer) was found in most patients (92%) even when no palpable mass was evident (85%); this carcinoma is often multifocal (73%). Mammography fails to identify the underlying disease in many patients with no palpable mass and multifocal underlying disease (64%). Patients with Paget's disease and a palpable mass have a much greater incidence of invasive cancer, multifocal lesions, and positive lymph nodes, and have worse survival. CONCLUSIONS: Although some patients with Paget's disease might be well treated by breast conservation therapy, many patients have underlying multifocal carcinoma (including invasive cancer), which can be inapparent by examination and mammography. Selecting candidates with disease amenable to complete excision without mastectomy is problematic.

J Gynecol Obstet Biol Reprod (Paris) 2000 Nov;29(7):655-61

Is mammography useful in Paget's disease of the breast?

Le Pennec A, Lacroix J, Fournier LS, Schmutz GR, Boute V, Crouet H, Denoux Y

Service de Radiologie Generale, C.H. Argentan, Service IRM, C.H.U Caen.

PURPOSE: Interest of the mammogram in Paget's disease of the breast, especially for a therapeutic decision in otherwise asymptomatic women with Paget's disease, who would be candidates for conservative treatment. Materials and methods. 61 women with histological Paget's disease of the nipple, treated by mastectomy, were retrospectively analyzed with clinical, radiological and pathological correlations. RESULTS: An underlying carcinoma was found in 60 cases (98.4%), atypical epithelial hyperplasia in one. In the 24 women without breast palpable mass, 17 (71%) had a normal mammogram, 12 (50%) had carcinoma with an invasive component, 14 (58%) had a cancer at a distance from the nipple, 17 (71%) had a multifocal carcinoma. All 37 women with a palpable mass had a pathological mammogram, 36 of them had carcinoma with an invasive component, 35 (95%) a cancer at a distance from the nipple, 31 (84%) a multifocal carcinoma. CONCLUSION: Mammogram is of limited value in management of Paget's disease of the breast for women without breast palpable mass; it can not predict the site of malignancy, nor the invasive component.