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Inflammatory breast cancer (IBC) is characterized by a peculiar geographic distribution in incidence, being described as more common in Tunisia and the region of North Africa. The authors performed a systematic review of published literature on rapidly progressing breast cancer and IBC in Tunisia and analyzed the evolution in epidemiology, clinical presentation, treatment, and therapeutic results. They collected, analyzed, and compared all the indexed Tunisian articles about rapidly progressing breast cancer and IBC since the 1970s opening of the Institut Salah Azaiz Institute in Tunis. In the 1970s, rapidly progressing breast cancer diagnosis was based on the Poussee Evolutive classification (1-3). Since the 1990s, IBC diagnosis has been based on the American Joint Committee on Cancer Poussee Evolutive 3/T4d staging. The authors compared the historical data to the most recent publications in terms of epidemiology, clinical features, treatment, and therapeutic results. The most important historical report of rapidly progressing breast cancer concerned 340 patients, representing 58.5% of a cohort of 581 breast cancer patients collected from 1969 to 1974, including 320 (55.2%) with inflammatory signs, 37(6.5%) with Poussee Evolutive 2, and 283 (48.7%) with Poussee Evolutive 3. Subsequent papers have documented a steady decrease in incidence to the current 5% to 7% T4d/IBC. Since the 1970s, Poussee Evolutive in premenopausal woman has increased from 52.5% to 75%; rural predominance has persisted. The 5-year overall survival reached 28% by the year 2000. The authors' analysis demonstrated a trend of decreasing incidence of IBC diagnoses from 50% to presently

BACKGROUND An early immunologic study suggesting that a virus similar to the mouse mammary tumor virus (MMTV) was associated highly with breast carcinoma in Tunisian patients, compared with patients in the United States, led the authors to examine different breast carcinoma populations by using more current molecular techniques. METHODS Thirty-nine paraffin blocks were selected for sequencing of the 250-base pair segment of the MMTV from patients with breast carcinoma who were seen and treated at the Institut Salah Azaiz in Tunisia. Fifteen of those blocks were examined under code by a second laboratory, which used a different methodology and was blinded to the results of the first laboratory, and 14 blocks were analyzed successfully. RESULTS The comparison of Tunisian patients and patients from other countries clearly showed a significantly higher proportion of tumors with MMTV-like sequences in the Tunisian series of patients. There was complete reproducibility of data between the two laboratories. Using the results from the first laboratory and similar studies from the literature, detection of the MMTV-like env gene sequence showed an important geographic pattern with a significantly higher percentage of positive patients with breast carcinoma in Tunisia (74%) compared with patients with breast carcinoma in the United States (36%), Italy (38%), Australia (42%), Argentina (31%), and Vietnam (0.8%) CONCLUSIONS The findings provided increased evidence for a human breast carcinoma virus with geographic differences in prevalence. The geographic differences were compatible with studies of MMTV in wild mice; thus, the data were plausible biologically. Cancer 2004. © 2004 American Cancer Society.

A form of breast cancer characterized by rapid disease progression, inflammation, and edema is found in approximately 55% of the breast cancer patients presenting at the Institute Salah Azaiz, Tunis (Tunisia). In 581 patients seen between January 1, 1969, and December 31, 1974, we examined age, place of residence, reproductive history, delay in seeking treatment, and blood gropu as potential risk factors to determine the distinction between the rapidly progressing disease and the less aggressive form. Rural residence, blood type A, and recent pregnancy are risk factors among premenopausal women, but older age, rural residence, blood type A, late menarche, and delay in diagnosis are associated with postmenopausal rapidly progressing breast cancer. The most significant risk factors were rural residence and blood type A. Rapidly progressing breast cancer was diagnosed in two of every three breast cancer patients coming from a rural environment. Forty-three percent of 203 patients with rapid disease progression were blood type A, a significantly higher percentage than the 33% found in the general Tunisian population and the breast cancer patients without evidence of rapidly progressive disease. We observed that the risk factors for disease progression were quite different from those reported to influence the incidence of breast cancer.

Based on two pretreatment evaluations, doubling time (DT) was calculated in 75 cases of invasive breast cancer (BC). The cases studied were more or less equally distributed between three DT groups: fast-growing tumors (DT less than 90 days), intermediate cases (DT between 90 and 180 days), and slow-growing tumors (DT greater than 180 days. A correlation was found to exist between DT and patient age and, to an even greater extent, between DT and pathologic prognostic indicators such as histologic grading and nuclear grade. Inflammatory symptoms were not associated with DT, but were closely related to the size of the tumor and regional lymph node involvement. The date of detection of distant metastases depended heavily on the DT of the BC:BC with shorter DT = earlier metastatic spread. The presence of inflammatory signs was also decisive: within each DT category, inflammatory BC metastases were both more frequent and precocious.

Biopsy specimens from 85 Tunisian breast cancer patients were compared with those of 95 American breast cancer patients for estrogen receptor (ER) and progesterone receptor (PR) levels. Tunisian patients with rapidly progressing breast cancer (RPBC) had lower ER levels than American patients or Tunisian patients without evidence of RPBC. Lower ER levels in the earliest stage of RPBC, which presents without inflammatory signs, supported epidemiologic and pathologic studies indicating that rapid growth as reported by the patient is an important aspect of RPBC. Low ER levels were generally found in young, premenopausal Tunisian women with advanced RPBC; multivariate analyses suggest that age was the most important correlating factor. In the Tunisian patients, ER levels showed a direct correlation with response to therapy. No consistent relationship between American and Tunisian patients or subgroups was observed for PR levels. These results indicate the need for reevaluating the routine use of oophorectomy in RPBC.

Nine cases of Mediterranean lymphoma with alpha heavy chain disease are described. All patients were young, aged between 11 and 22 years. Neither sex predominated in the series. The clinical presentation of the disease was either gastrointestinal, with chronic diarrhea and malabsorption, or neoplastic, with tumors frequently associated with either obstructive or perforative complications. Finger clubbing and retardation of physical growth (height and weight) and secondary sexual maturation were usually evident. The laboratory manifestations of the malabsorption syndrome were scant and generally not specific. The intestinal lesions predominated in the beginning of the small bowel, and their gross appearance varied from one case to another: diffuse thickening of the intestinal wall, alone or associated with tumors, or isolated segmentary tumors. Massive mesenteric lymph node enlargement was present in all cases; in some cases hepatic, splenic, or extra-abdominal lymph node spread was noted. Histologically, these lesions demonstrated a varied cellular morphology, but seemed to belong constantly to the B-lymphocytic line. The secretion and excretion by these cells of an abnormal IgA (devoid of light chains), which was revealed by immunoelectrophorectic study of the patients' sera, was the main biochemical abnormality of the disease. This disease presents several problems: 1) its relationship with other intestinal lymphomas; 2) the nature and the degree of malignancy of the intestinal cellular infiltrates; and 3) its identification as a clinicopathologic entity, with the possibility that infectious and genetic factors are significant in its etiology and pathogenesis.

Clinical and radiographic examination of 581 patients with histologically veri-fied breast cancer has permitted us to define a subgroup having a significantly poorer prognosis than other patients. Their condition, called “poussee evolu-tive” (rapidly progressing), is characterized by rapid tumor growth and/or inflammation adjacent to the tumor. Statistical analysis of the survival of Mo patients (412 of the 581) shows that the diagnosis of “poussee evolutive” provides prognostic information beyond that given by T and N classifications and after delay between initial symptoms and diagnosis has been considered. Six years of clinical experience with this condition are discussed. Cancer 40:376–382, 1977.