Clinicopathological features of mammary Paget's disease: a single-center experience in Turkey

Background/aim: Paget's disease (PD) of the breast is a very rare presentation of breast malignancy, accounting for 1%­3% of all primary breast tumors. We aimed to evaluate and compare the clinicopathological features and clinical outcome of PD accompanied by in situ carcinoma and invasive cancer. Materials and methods: We used the archive of our pathology laboratory retrospectively for age, sex, history of surgery, histopathological findings, treatment modalities, and follow-up information. We used the Kaplan­Meier method for survival analysis. Results: There were 46 female patients diagnosed with PD. In 39 (84.7%) patients, invasive carcinoma accompanied PD, while 7 (15.3%) patients had ductal carcinoma in situ. The median age at diagnosis was 53.5 years. The median follow-up period was 47 months. Of the 39 invasive carcinoma, 10 (25.6%) died during the follow-up period. Invasive ductal carcinoma group had a mean overall survival of rate of 57.8 ± 6.6 months. According to univariate analysis, only the tumor type was found to impact overall survival (p < 0.001). Conclusions: The current study displayed the tumor type as the only parameter affecting overall survival in the invasive carcinoma group. Although it was not statistically significant, breast cancers accompanied by PD were found to be predominantly advanced stage tumors, high grade, hormone receptor negative, and HER2 positive.

Prevalence of mammary Paget's disease in urban China in 2016.

No national data have been available on descriptive epidemiology of mammary Paget's disease (MPD) in China. This population-based study aimed to estimate the prevalence of MPD and its pattens by sex, age and area in China. We conducted a population-based study using data in 2016 from China's Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion residents. MPD cases were identified based on the diagnostic names and codes in claim data. A total of 825 patients of confirmed diagnosis of MPD were found during the study period. The prevalence of MPD in 2016 was 0.42 per 100,000 population (95% CI 0.19 to 0.73), with marked female predominance. The prevalence rates peaked at 40-59 years and ≥ 80 years in females and males, respectively. The prevalence rates varied among different regions, ranging from 0.06 (95% CI 0.00 to 0.23) in Northeast China to 1.21 (95% CI 0.07 to 3.72) in Northwest China. MPD showed marked female predominance in China. Chinese female patients were much younger, with lower prevalence than that in the United States. Obvious sex difference in the age pattern of MPD prevalence was also observed in China.

Paget disease of the breast: A national retrospective analysis of the US population.

BACKGROUND: Paget's disease of the breast is rare. The National Cancer Database (NCDB) is one of the largest tumor databases in the United States. METHODS: We queried the NCDB to identify male and female patients with Paget's disease of the breast who were treated from January 1, 2004, through December 31, 2015. No age limitations were applied. Descriptive statistical analysis and survival analysis were performed. RESULTS: We analyzed the demographic, disease, and treatment characteristics of 7,191 patients with Paget's disease of the breast. The median (range) age was 64 (20-90) years. Only 2.1% of patients were men, and 85.4% were white. The most common treatment was complete mastectomy (65.3%), followed by partial mastectomy (30.3%). Tumor destruction was performed in 0.1% of patients, and 4.3% of patients did not undergo any surgery. We examined survival in the subset of 6,864 patients who were treated surgically with complete mastectomy or partial mastectomy. The 5-year survival rate after surgery was 82.5% (95% CI, 81.1%-83.9%). Factors associated with shorter survival were older age, black race/ethnicity, higher tumor grade, regional lymph node metastasis, higher cancer stage, metastatic cancer, and larger tumor size. CONCLUSIONS: Paget's disease of the breast usually affects patients older than 60 years, and the most common treatment is complete mastectomy. The 5-year overall survival rate of patients with Paget's disease of the breast is greater than 80% but is lower among older and black people.

Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.

BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD. RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS. CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.

Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011.

BACKGROUND: Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level. METHODS: The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study. RESULTS: Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P < .001). Compared with Her2 negative tumors, Her2 positive tumors were larger (2.6 vs 2.2 cm, P < .001), more likely to have positive nodes (39% vs 31% P < .001), have lymphovascular invasion (30% vs 20%, P < .001), and be high grade (56% vs 29%, P < .001). There were also differences by histology: invasive ductal 16.4%, invasive lobular 5.5%, tubular 2.3%, inflammatory 36%, and Paget's with invasion 59%. When adjusted for age, race, tumor size, and nodal status Her2 positive tumors were much more likely to receive chemotherapy (odds ratio = 5.5, confidence interval = 5.2 to 6.0) and somewhat less likely to undergo breast preservation (odds ratio = .78, confidence interval = .76 to .80). CONCLUSIONS: Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics.

[Diagnosis and treatment for Paget's breast cancer: state of the art].

Breast cancer is the most common cancer in women. According to WHO experts in the world each year there are revealed from 800,000 up to 1 million new cases of breast cancer. In the structure of malignant tumors morbidity among female population, in Russia in 2012 breast cancer ranked the first place (20.7%) and remained the leading malignant pathology in women. Paget's breast cancer is a rare form of breast cancer that occurs in the mouth of the excretory ducts of the nipple, which characterized by lesion of the nipple and large ducts, often with the formation of tumor in the breast. This rare abnormality occurs in 0.5-5% of all cases of breast cancer.

Histopathological features of breast cancer in Al-Madinah region of Saudi Arabia.

OBJECTIVES: To observe the frequency of breast cancer among Saudi patients and to highlight the age variations and features of advanced cancer. METHODS: A retrospective study of breast cancer biopsies from all Saudi patients performed between January 2006 and December 2013 in King Fahad Hospital, Al-Madinah, Kingdom of Saudi Arabia. All the available demographic and tumor related data was analyzed. RESULTS: Of 1005 breast tissues reviewed, 982 specimens were from female, and 23 from male patients. In females, 398 specimens (40.5%) were diagnosed as malignant. Invasive ductal carcinoma (IDC) (85.2%) was most common, followed by ductal carcinoma in situ (8%), and invasive lobular carcinoma (2.7%). The mean age of Saudi females with IDC was 46.9 years. Approximately 48.7% IDC were Grade III tumors. A tumor size >2.5 cm  was found in 61.1% patients, whereas axillary nodal metastasis was present in 57.1% and lympho-vascular invasion in 64.1% who underwent axillary nodal dissection. In males, 4 specimens (17.4%) were malignant (all IDC). CONCLUSION: Our finding are consistent with previous reports of breast cancer being diagnosed in younger age group, in advanced stages, and with features of aggressive behavior; which signals the urgency for implementation of breast screening programs. 

Paget's disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis.

BACKGROUND: Paget's disease is a rare clinical and histological type of local recurrence (LR) after breast cancer treatment both in case of conservative surgery or nipple-sparing mastectomy (NSM) with or without intraoperative radiation. METHODS: We performed an analysis of 861 NSM with electron beam intraoperative radiotherapy (ELIOT) patients treated at the European Institute of Oncology from 2002 to 2008, focused on Paget's disease local recurrence. RESULTS: In 861 patients (713 invasive carcinoma and 148 intraepithelial neoplasia), there were 36 local recurrences (4.18%), and among these were 7 Paget's disease local recurrences (0.8%). Median follow-up was 50 months. Four cases presented with nipple areola complex (NAC) erosions, two crusted lesions, and one ulcerated NAC. The average latency period from the NSM to Paget's disease local recurrence is 32 months (range, 12-49). Complete NAC removal was performed in all seven recurrences. The average follow-up after NAC removal was 47.4 months (range, 20-78). We found neither locoregional relapse nor metastatic event in this group. All patients were alive without disease. CONCLUSIONS: Paget's disease local recurrence can be found in a significant proportion after NSM. Any suspicious lesion on NAC requires prompt pathological confirmation. Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormonal receptor, high pathological grade, overexpression of HER2/neu, and "HER2 positive (nonluminal)" subtype tend to be significantly associated with more Paget's disease local recurrence and should be followed carefully.

Paget's disease of the breast: the experience of the European Institute of Oncology and review of the literature.

BACKGROUND: Paget's disease of the breast is an uncommon presentation of breast malignancy, accounting for 1-3% of all the breast tumors and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma, or without any underlying neoplasia. In the literature, different methods are used for the treatment. Mastectomy with or without axillary dissection has been considered as the standard treatment procedure for many years. Several studies have already shown that breast conservation with radiation therapy is an oncologically safe option. Regarding the axillary approach, several studies have documented the presence of positive sentinel lymph node even in Paget's disease alone. The objective of this study was to retrospectively analyze outcome of patients affected by Paget's breast disease and to define our institutional experience. PATIENTS AND METHODS: Between May 1996 and February 2003, 114 patients with confirmed Paget's disease of the breast were retrieved and underwent surgery at the European Institute of Oncology of Milan, Italy. The median age of the patients was 54 years at the time of the diagnosis. In our study, the histopathological examination of the operated specimen revealed one hundred seven patients with Paget's disease associated with an underlying invasive or non invasive carcinoma, and seven patients without underlying carcinoma. Patients underwent either conservative breast surgery or mastectomy, with or without sentinel lymph node biopsy and/or axillary surgery. Each patient was evaluated after surgery at a multidisciplinary meeting to selecting systemic therapy. RESULTS: Seven patients had "pure" Paget's disease of the breast and one hundred seven had the disease associated with an underlying carcinoma. As surgical techniques 71 mastectomies and 43 breast conserving surgeries have been performed. Complete axillary dissection was done in patients with clinically positive lymph node and/or sentinel lymph node biopsy positive. Sentinel lymph node biopsy was performed in nineteen patients with invasive component and five were positive and underwent axillary dissection. Eleven sentinel lymph node biopsies were done in patients with non invasive component and none of them was positive. Adjuvant systemic therapies were based on the final tumor, node and metastasis stage: thirty patients received adjuvant chemotherapy alone, fourteen received endocrine treatment alone, twenty-six patients were evaluated to receive both chemo and endocrine therapy. The median duration of follow up was 73 months and was updated in the last 6 months. Five patients developed local recurrence, one had regional recurrence, another two had loco-regional recurrences and fourteen had distant metastasis as a first event. Malignancy-related deaths were censored in the statistical analyses cancer for and due to another tumor in eleven patients. Additionally, deaths were not related to malignancy totally in thirteen patients. CONCLUSIONS: Screening examination and imaging techniques are fundamental. Breast conserving surgery combined with breast irradiation for patients with invasive and non invasive breast carcinoma has become the treatment of first choice. All surgical conservative approaches should include the complete nipple-areolar complex and margins of resected specimen free of tumor. Thanks to the evolution of the conservative approach, good cosmetic result can be obtained. To be informed about the axillary lymph node status and to avoid the patient to have a second surgical approach, sentinel lymph node biopsy should be performed.

Mammary and extramammary Paget's disease.

Paget's disease is an intra-epidermal adenocarcinoma seen over the nipple/areola (mammary Paget's disease) or in extramammary body zones, such as the anogenital and perineal skin and the axilla. Mammary and extramammary Paget's disease share many common clinicopathological features but also show several differences, namely, with regard to pathogenesis and association with underlying malignancies. Indeed, mammary Paget's disease is as a rule associated with an underlying breast carcinoma whereas association of extramammary Paget's disease with underlying (skin or visceral) malignancies occurs much less frequently. We review here the main clinicopathological and therapeutic features of mammary and extramammary Paget's disease.

Paget disease of the breast: changing patterns of incidence, clinical presentation, and treatment in the U.S.

BACKGROUND: Paget disease is an uncommon presentation of breast cancer that increased in incidence in the U.S. between 1973 and 1987. Characterized by malignant crusting or ulceration of the nipple, Paget disease can present in 1 of 3 ways: 1) in conjunction with an underlying invasive cancer, 2) in conjunction with underlying ductal carcinoma in situ (DCIS), or 3) alone without any underlying invasive breast carcinoma or DCIS. Paget disease can be treated with breast conservation by undergoing central lumpectomy. The objective of this study was to determine how the incidence, presentation, biomarkers, operative approach, and outcome of Paget disease have evolved in the U.S. since 1988. METHODS: Between 1988 and 2002, 1738 women who were diagnosed with Paget disease were reported in the 9 registries of the Surveillance, Epidemiology, and End Results Program. To the authors' knowledge, the current study on tumor characteristics, surgical intervention, and survival represented the largest series of Paget disease ever reported. RESULTS: Although the overall incidence of breast cancer increased between 1988 and 2002, the incidence of Paget disease concomitantly decreased by 45% (95% confidence interval, from -35% to -53%). This decreasing incidence was greatest for Paget disease associated with invasive cancer or DCIS. Invasive cancer associated with Paget disease more commonly was estrogen receptor negative, progesterone receptor negative, and of high histologic grade. Even when 60% of the disease was located centrally, only 293 of 1642 patients with Paget disease (18%) who were treated surgically underwent central lumpectomy. Patients with Paget disease who underwent breast conservation had outcomes equivalent to the outcomes among patients who underwent mastectomy. CONCLUSIONS: The incidence of Paget disease associated with underlying invasive cancer or DCIS decreased since 1988. Patients who underwent central lumpectomy and patients who underwent mastectomy for Paget disease had similar outcomes; nonetheless, most patients who were candidates for preservation underwent mastectomy.

[Paget's disease of the breast].

Paget's disease of the breast is a rare malignancy of the nipple-areola complex, comprising 0.5-4% of all breast cancers which is often associated with an underlying in-situ or invasive carcinoma in the breast parenchyma. It is manifested by progressive eczematoid changes of the areola with persistent soreness or itching. Due to the seemingly benign appearance, diagnosis is often delayed by more than six months. There are two main theories regarding the histogenesis of the disease: the epidermotropic and the in-situ transformation. The first suggests that Paget cells are ductal cells that have migrated from an underlying carcinoma of the breast parenchyma to the epidermis of the nipple. The second postulates that nipple keratinocytes undergo transformation into malignant cells independent from any pathology within the breast parenchyma. Prognosis is determined by the nature of the concurrent tumor in the breast. In 50% of cases a palpable mass is evident and it usually represents an infiltrating carcinoma with involved axillary lymph nodes. In the absence of a mass the prognosis is invariably better as it usually reflects a noninvasive tumor (DCIS). The standard treatment has been mastectomy. However in an era when breast conserving surgery is implemented even for advanced infiltrating breast tumors, there might be a role for such a treatment for selected patients with Paget's disease.

Morphological types of breast cancer in family members and multiple primary tumours: is morphology genetically determined?

BACKGROUND: We conducted the present study to determine whether breast cancer morphology is genetically determined. METHODS: Using the nationwide Swedish Family Cancer Database, which includes data on 10.2 million individuals and over 25,000 morphology-specific breast cancers, we followed morphological types in familial cancers between mothers and daughters and between sisters. Additionally, we recorded morphological data in women who presented with two primary breast cancers and in those who presented with an invasive and in situ breast cancer. We used kappa statistics to examine the association between genetics and morphology. A kappa value of 0 indicates that the process is random and a value of 1 indicates that it is completely determined (i.e. genetic); values between 0.40 and 0.60 are considered to indicate a moderately determined process. RESULTS: The study sample included a total of 25,730 first and 3394 second invasive breast cancers, and 2990 in situ breast cancers. Ductal, lobular, tubuloductal and comedo were the most common invasive types. We identified 164 mother-daughter pairs with breast cancer of a defined morphology, yielding a low kappa value of 0.08. Among 100 sister pairs the kappa value was 0.002. In individuals with two primary breast cancers the kappa values were 0.22 and 0.01 for two invasive and in situ-invasive pairs, respectively. However, for a tumour with a subsequent tumour detected in the contralateral breast less than 1 year later the kappa value was 0.47. CONCLUSION: The data suggest that breast cancer morphology is not genetically determined. However, because of mixed morphologies and the overwhelming prevalence of ductal morphology, the results for rare morphologies should be interpreted with caution.

Identification of women at high genetic risk of breast cancer through the National Health Service Breast Screening Programme (NHSBSP).

Breast cancer is a multifactorial disease with an inherited predisposition being implicated in around 5% of all cases. Using previous epidemiological data assessing risks for the relatives of women with breast cancer, we have identified 154 women (from a screened population of 35,505) and 289 of their relatives between 50 and 64 years who have more than twice the age related risk of developing breast cancer. This constitutes 1.24% of the breast screening population attending the North East Scotland NHSBSP. For each woman identified to be at high risk, we have found 1.87 female relatives between 50 and 64 years and 1.85 relatives under 50 years also to be at high risk. Around 78% of the women identified with a significant family history of breast or other cancer have attended for counselling about their risks. The breast screening programme can be used to identify women at high risk of breast cancer in order to offer them (and their relatives) access to genetic counselling and appropriate screening.

Paget's disease of the breast.

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.

Breast cancer in Nigeria.

Breast cancer as seen in 116 Nigerian women over a 5-year period, 1974 to 1979, at the University of Benin Teaching Hospital, Benin, Nigeria, is presented. The disease occurs one decade earlier in Nigerians and is mainly a disease of premenopausal and perimenopausal women. Reflecting their relative youthfulness, more than 10% of them are pregnant or lactating on presentation. The most common histologic finding is anaplasia with very unfavorable histological grade. Breast cancer does not seem to have a different biologic behaviour in Nigerians, but it carries a truly bleak prognosis because many of the patients present with incurable disease that is close to its end stages.

Paget's disease of the male breast.

Paget's disease of the breast is a malignant lesion consisting of Paget cells in the epidermis and an underlying ductal carcinoma of the breast tissue. It is estimated that perhaps 3% of female breast carcinoma cases are Paget's disease. If one estimates male breast carcinoma to be approximately 1% of the rate in the female population, then Paget's disease in men is clearly a rare clinical event. Although Paget's disease has an epidermal component, little attention has been given to this entity in the dermatologic literature. We present a case report of this disease in an elderly male patient and comment on the clinical features which should alert the physician to the presence of the malignancy.

Prognosis of mammary carcinoma in young women.

One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.