Ten-year results utilizing chemotherapy as primary treatment in nonmetastatic, rapidly progressing breast cancer.

Eighty-three patients with rapidly progressing breast cancer (RPBC) were entered into a study of primary chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and subsequent randomization to surgery or radiotherapy for control of local/regional disease. Eighty-three of these patients with redness, warmth, and edema compatible with clinical "inflammatory breast cancer" served as the focus for our analysis of factors associated with improved survival. The stage-specific disease-free intervals (DFI) of 36 and 21 months were substantially longer than in the earlier series (26 and 16 months) from the same institution. The evaluation of individual prognostic indicators revealed that the initial tumor size and the initial response to chemotherapy were the two independent factors most important in predicting the DFI. The continuing unmaintained 1-year remission in at least 12 patients supports the rationale for aggressive therapy in RPBC or "inflammatory breast cancer."

Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution.

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.

Immunoproliferative small intestinal disease without alpha-chain disease: a pathological study.

Biopsy specimens taken during exploratory laparotomy provided the material for a pathological study of 23 cases of nonsecreting immunoproliferative small intestinal disease (Mediterranean lymphomas without alpha-chain disease). The distinctive pathological feature of immunoproliferative small intestinal disease, i.e., a diffuse lymphoid infiltration, was present in the mucosa and submucosa of all or a major part of the small intestine. It was composed of a low- or intermediate-grade malignant lymphoid proliferation associated in 19 of 23 cases with benign-appearing follicular lymphoid structures. These follicular figures were surrounded and partially destroyed by the lymphoma cells. This association strongly resembles the newly described non-Hodgkin's lymphoma entities of perifollicular or parafollicular cell origin. Gross tumors of the small intestine were found in association with the diffuse lymphoid infiltration in 10 cases. They often constituted foci of lymphoma with a higher grade of malignancy. Mesenteric lymph node involvement was frequent and generally in direct ratio to the severity of intestinal involvement. A comprehensive study of the lesions observed in these cases led to the hypothesis that nonsecreting immunoproliferative small intestinal disease could result from the malignant change of perifollicular B cells; during an initial period the tumoral cells retain circulating and homing properties that explain their infiltrative and extensive method of spreading. The possible subsequent emergence of more aggressive subclones of noncirculating malignant cells could then explain the associated inconstant fungating tumor foci. Further studies using more sophisticated immunohistochemical techniques are necessary to establish the meaning of the hyperplastic lymphoid follicles, the possible etiologic role of benign nodular hyperplasia, the exact identification of the tumor cells, and the relationship of nonsecreting immunoproliferative small intestinal disease to closely related alpha-chain disease.

Results of laparotomy in immunoproliferative small intestinal disease.

Immunoproliferative small intestinal diseases (IPSID), previously known as Mediterranean Lymphomas, constitute more than 60% of the non-Burkitt's small intestinal lymphomas in Tunisia. A multidisciplinary study of IPSID was undertaken by the Tunisian/French Lymphoma Study Group in 1980 to reach a better understanding of the two subgroups of the disease: secreting IPSID (essentially alpha-chain disease [ACD]); and nonsecreting IPSID (NS-IPSID) (extensive small intestinal lymphomas without gammopathy). The results of initial exploratory laparotomy performed in 38 cases of IPSID (17 ACD and 21 NS-IPSID) are described here, and show notable similarities between the two groups: the extensive pattern of the abnormal cell infiltrate along the major part of the small intestine; frequent and extensive involvement of the mesenteric lymph nodes; the existence of several degrees of severity in small intestinal mesenteric lymph nodes; and other intraabdominal organ involvement. Certain differences also were observed: the relatively high degree of tropism of the NS-IPSID towards the gastric mucosa which was absent in the ACD of this series; and the more frequent involvement of the entire length of the small bowel in ACD. In spite of these discrete differences, the IPSID form a homogeneous group which is definitely distinguishable from the segmentary small intestinal lymphomas known as Western-type, and which account for approximately one third of our non-Burkitt's small bowel lymphomas.

[Cancer of the cervix uteri in Tunisia. Clinical presentation and development over a 10-year period]. / Le cancer du col utérin en Tunisie. Présentation clinique et évolution au cours d'une période de 10 ans.

Carcinoma of the cervix is still common in Tunisia, where it occupies second place among malignant diseases in women. Accounting for 17% of the female population of the National Cancer Institute of Tunis, it is preceded only by breast cancer (27%). Study of the factors concurrent with the origin of carcinoma of the uterine cervix seems to indicate that its decrease is secondary to the lowered average age at marriage, to the fall in the reproduction rate among the population at large, and to improved socio-economic conditions among the poorer classes. Study of clinical features observed during two separate periods of 10 years shows a modification in the physiognomy of this cancer, with, notably, a larger frequence of lower stages (45% of stage II in 1984 vs 20% in 1974) and a slight tendancy towards the discovery of smaller non - or early - infiltrating tumors (4% in 1984 vs 0% in 1974). Efforts must continue to be made in the domaine of early detection, especially among the "high risk" population.

[Juvenile secretory carcinoma of the breast. Apropos of a case in a 4-year-old girl]. / Carcinome sécrétant juvénile du sein. A propos d'une observation chez une fille de 4 ans.

The authors report the case of a juvenile secretory carcinoma of the breast in a 4 year old girl. The study of the first local excision leads to the thought of a "duct ectasia with a luminal benign papilloma". At the age of 6 years, there is a local relapse. A second local excision is performed and connected with simple mastectomy and an axillary node sampling. The pathological examination shows the aspect of a multifocal secretory juvenile carcinoma of the breast without lymph node axillary metastase. The authors emphasize the cystic appearance of the first tumor and the distinctive histologic pattern of this particular breast carcinoma.

Breast cancer in women under 30 years of age.

Conflicting opinions exist concerning clinical and pathological presentation, as well as evolution and prognosis, of breast cancer in young women. The roles of associated pregnancy and lactation on these parameters is also unclear. These two conditions are studied in the present work through the comparison of two breast cancer patient age groups: patients under the age of 30 (Group A) and premenopausal patients aged 45-49 (Group B). Rapidly growing and/or inflammatory breast cancer (rapidly progressing breast cancer: RPBC)--a special form of Breast Cancer with a poor prognosis very frequent in the Tunisian breast cancer population--was more often present among Group A patients. This difference is a consequence of the more frequent association of this breast cancer group with pregnancy or lactation; nearly all the cases of breast cancer associated with pregnancy or lactation are RPBC. For breast cancer without the pregnancy/lactation association, the younger group generally shows poorer histological grading and more severe evolution. The number of patients in our study is not really sufficient to allow statistically significant conclusions, but it does seem clear that young age and associated pregnancy/lactation are aggravating factors in Tunisian breast cancer patients.

Hormone receptors in rapidly progressing breast cancer.

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.

Increased incidence of mouse mammary tumor virus-related antigen in Tunisian patients with breast cancer.

Biopsies obtained from 74 Tunisian women with breast cancer (33 cases), benign breast disease (17 cases), and cervical cancer (24 cases) were assayed for the presence of an antigen cross-reacting with gp52 of the mouse mammary tumor virus (MMTV) in order to determine the frequency and possible prognostic significance of this antigen in a form of rapidly progressing breast cancer designated poussée évolutive or PEV. Antigen was detected in 23/33 breast carcinomas (70%) but in none of the 41 control specimens. An evaluation of reactivity according to tumor aggressiveness and survival could be performed in retrospect on 29 of the breast cancer patients with a follow-up of up to 11 years. The frequency of gp52-related antigen was similar in the patients with the most aggressive form of PEV with inflammatory signs (8/12 or 67% positive) and those breast cancer patients without PEV (12/17 or 71% positive). Within each of the two groups, PEV+ and PEV 0, no correlation was observed between the presence or absence of antigen and the disease-free interval or survival. We conclude that the identification of gp52-related antigens in the breast cancer biopsies from North African women has implications different from those observed in other populations. While thus far not indicative of disease aggressiveness and prognosis, the higher frequency of detectable antigen in comparison to biopsies obtained from patients born in the United States and Europe may have relevance to the etiology and pathogenesis of the disease.

Histopathological features of rapidly progressing breast carcinoma in Tunisia: a study of 94 cases.

The histological features of 94 cases of carcinoma of the breast seen in Tunisia were recorded and subsequently correlated with the clinical classification of the patients in terms of poussée évolutive (PEV) categories. Histological features analyzed in the breast tissues and skin included tumor type, nuclear grade, number of mitoses, involvement of the dermis, cutaneous inflammatory infiltrate and edema. Twenty-eight percent of the cases in which the skin was examined showed tumor emboli in the lymphatics of the dermis. The frequency of cutaneous permeation correlated with the PEV categories. The percentage of cases with nuclear grade 3 was higher for the group with rapid progression of the disease (PEV 1,2,3) than for the cases belonging to the PEV-0 category (90% versus 64.2%). The present study demonstrates that a large proportion of breast carcinoma patients in Tunisia suffer from "inflammatory carcinoma of the breast".

Preliminary results of primary systemic chemotherapy in association with surgery or radiotherapy in rapidly progressing breast cancer.

112 Tunisian patients with rapidly progressing breast cancer (RPBC) were entered into a clinical trial evaluating combination chemotherapy as a primary form of treatment before surgery or radiotherapy. Three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) were administered at monthly intervals; patients were then randomized to surgery or radiotherapy to control the primary tumour, and 12 more cycles of CMF followed local/regional therapy. RPBC was sensitive to CMF; after only 3 cycles, 11% of evaluable patients showed complete remission and 78% had at least 25% diminution in tumour size. The disease-free interval (DFI) was substantially greater in this series than in a previously reported series treated by surgery and/or radiotherapy alone. No difference in DFI was found between patients randomized to receive surgery and those randomized to receive radiotherapy. Postmenopausal patients responded to CMF as well as premenopausal patients. Combination chemotherapy appears to play an important role in the control of RPBC, an aggressive malignancy often resembling inflammatory breast cancer.

Studies on the role of cellular immunity and genetics in the etiology of rapidly progressing breast cancer in Tunisia.

It has been suggested that poussée évolutive (PEV) or rapidly progressing breast cancer (RPBC) represents a failure in the host immune system to control the proliferation of breast cancer cells. To evaluate this possibility, we have performed in vivo and in vitro assays of cellular immunity in Tunisian patients with breast cancer. Studies of delayed hypersensitivity using microbial antigens and in vitro including lymphocyte transformation tests and measurements of B and T cells indicated that RPBC patients had an immune response comparable to that of breast cancer patients without evidence of rapid progression. Normal Tunisians were more immunocompetent, however, an appeared to have a higher level of immune activity than normal individuals in the United States. In a second, independent series, an increased frequency of blood group A was found in RPBC patients, suggesting a genetic predisposition to this form of breast cancer. However HLA typing for A, B and DRW antigens revealed no specific RPBC-associated HLA antigen. Our studies clearly demonstrate that RPBC, or PEV, is not a reflection of immunodeficiency.

Epidemiologic features of rapidly progressing breast cancer in Tunisia.

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.

Clinical and prognostic features of a rapidly progressing breast cancer in Tunisia.

Clinical and radiographic examination of 581 patients with histologically verified breast cancer has permitted us to define a subgroup having a significantly poorer prognosis than other patients. Their condition, called "poussée évolutive" (rapidly progressing), is characterized by rapid tumor growth and/or inflammation adjacent to the tumor. Statistical analysis of the survival of M0 patients (412 of the 581) shows that the diagnosis of "poussée évolutive" provides prognostic information beyond that given by T and N classifications and after delay between initial symptoms and diagnosis have been considered. Six years of clinical experience with this condition are discussed.