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Breast cancer is 100 times less frequent in males than in femalees. In this series the predominant histological form clearly was adenocarcinoma, present in 69 out of 73 patients. The patients' age varied from 7 to 82 years. In 91% of the cases, the malignancy presented as a painless, isolated tumour, often associated with retraction of the nipple. After 5 years 68% of patients operated upon immediately after diagnosis and 35% of those initially treated by radiations were still alive, as were 72% of patients with less than 7 cm tumours and 44.8% of those with larger tumours. It appears that breast cancer in males is less aggressive than is usually believed. Its histological features and its treatment are comparable to those of femal breast cancer.

The breast pathology files at the Institut Gustave-Russy in Villejuif, France, were searched for papillary cystadenomas and papillary carcinomas diagnosed between January 1, 1960, and December 31, 1974. A total of 158 cases were selected for this study; they were subclassified into 74 papillary cystadenomas, 63 papillary carcinomas, and 21 multiple papillomas. Spontaneous nipple discharge was the primary reason for consultation in 88% of solitary cystadenoma patients, 48% of multiple papilloma patients, and 23% of the carcinoma patients. The data support the benign nature of papillary cystadenoma inasmuch as none of the 73 patients treated with local excision developed cancer of the same breast, with only one patient having recurrence of the lesion. In contrast, multiple papilloma was associated with a high recurrence rate and malignant transformation. According to Scarff and Bloom's grading system, papillary carcinoma was found to be of low grade malignancy with a five-year survival rate of over 90%.

At the conclusion of this study based on 327 cases of breast cancer T1, T2 T3 (less than 7 cm) No, N1, Mo Pev O, treated by mastectomy and axillary dissection without previous treatment, it appears that the microscopic dissemination to the nipple has a pejorative prognosis value. The 5 years is 84 p. 100 when there is no nipple dissemination, 74 p. 100 when there is an intraductal nipple dissemination, and 57 p. 100 when there is lymphatic or interstitial nipple dissemination. These differences have a statistical value. This value does not seem connected with other pathological prognosis factors: tumors size, Bloom histopronostic grading, and the number of nodes invaded. The intra-mammary spread without nipple involvment has no prognostical value.

The prognostic implications of small emboli of carcinoma cells in the sinus margins of axillary lymph nodes ('clandestine' metastases) discovered by serial node sectioning at 2 mm intervals was analysed. All patients, previously untreated, were admitted between 1967 and 1978 and underwent mastectomy and axillary node dissection. Our study examined the risk of distant metastases of 1153 patients with from 0 to 3 involved axillary lymph nodes. A Cox multivariate analysis was performed, taking into account the classical prognostic factors (menopausal status, histoprognostic grade, and anatomic tumor size), and for nodal status including the notion of clandestine (CM) or parenchymal metastases (PM). Compared to patients without axillary metastases, patients with one node involved with CM had a relative risk of distant metastases of 1.7, identical to the risk for patients with one node with PM; and patients with one node containing PM and a second CM, had a relative risk of 2.2. Serial node sectioning discovers nodal metastases that would otherwise not be detected. These CM have important clinical implications and should be taken into account when considering adjuvant manipulations.

Between April and September 1986, 60 patients with osteosarcoma have been treated according to the T10 protocol in the Pediatrics Department of the Gustave Roussy Institute in Villejuif, France. Limb sparing could be achieved in 49 patients and amputation was necessary in 11. The necrosis of the primary tumor was total or subtotal in 33 cases and incomplete in the 27 others. With a median follow-up of 28 months, the actuarial survival is 85% at 48 months and the actuarial disease-free survival is 58%; the disease-free survival of "good responders" is 75% and 32% for "bad responders".

A retrospective study of 84 patients with liposarcoma treated at the Gustave Roussy Institute between 1956 and 1978 has elicited a number of factors which influence the prognosis, namely: (1) the site of the initial tumour: patients with liposarcoma of the head, trunk and extremities have a better survival rate than those with retroperitoneal tumours or tumours of the pelvic and pectoral girdles; (2) the histological type: differentiated forms have a brighter prognosis than undifferentiated forms; (3) the size of the tumour: tumours of less than 10 cm in diameter have a more favourable prognosis than larger tumours; and (4) the patient's age, which in fact correlates with the histological type. Local recurrences are common but do not seem to worsen the prognosis. The only curative treatment is surgery, but radiotherapy reduces the risk of local recurrences and chemotherapy may be considered in cases with poor prognosis.

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

We studied first the long term results in a series of 1 139 immediately operable breast cancers, treated by a protocol which gave an important role to extended radical mastectomy (radical mastectomy with internal mammary node dissection). No difference in survival was noted according to the surgical procedure used, and the extended mastectomy does not seem to have demonstrated its superiority. Its value could be judged in a more rigorous manner thanks to the results of an international therapeutic trial, comparing radical mastectomy with extended radical mastectomy. Results were improved by the extended procedure in only one sub-group of patients, whose tumours was located in central or inner quadrants, T1 or T2, with positive axillary nodes: these patients represents 13 per cent of patients with immediately operable tumors. Taking these results into account a new protocol has been adopted at the Institut Gustave-Roussy: T1 cancers will be the object of a therapeutic trial between conservative treatment and modified radical mastectomy. T2 (internal or central) cancers, with axillary nodal involvement will be treated by extended radical mastectomy. T2 tumors (external) and all T3 tumors will be treated by a modified radical mastectomy.

Evidence that supports the use of systemic, presurgical induction chemotherapy to render soft tissue sarcomas resectable or to minimize the extent of surgical excision is presented. Induction chemotherapy was administered in 34 cases of nonmetastatic soft tissue sarcomas. All patients had large tumors for which only mutilating surgery, if any, was possible. In 21 patients, a combination of Adriamycin (doxorubicin), cyclophosphamide, cisplatin, vindesine, and DTIC (DCPAV) produced two complete remissions (CR) and 6 partial remissions (PR). A combination of cyclophosphamide, vincristine, Adriamycin, and DTIC (CYVADIC) produced three PR in eight patients, and a combination of Adriamycin and ifosfamide (AI) produced two PR in five patients. After two to seven cycles of chemotherapy, 24 patients underwent surgery. In 19, gross tumor excision was performed; 12 proved to be microscopically fully resected. Disease in two patients entered CR with chemotherapy alone, but surgery was performed in both patients as well. Irradiation was administered in ten patients to produce or insure CR (eight cases of residual disease postoperatively), and in two patients with unresectable disease. Four patients with disease in CR after surgery also received radiation due to the initial massive tumor size. The Kaplan-Meier survival curves at 2 years showed 18% total survival in the patients in whom CR of disease was not achieved, and 80% survival in patients with disease in CR. Of the 22 patients with disease in CR (by all means), disease-free survival was 1 to 44 months (mean, 13.7). Disease currently remains in CR in ten patients with a mean follow-up of 13.6 months (3 to 34 months from end of therapy). Ten patients had a local recurrence following a CR after 3 to 44 months (mean, 15.3 months).

Abnormal nipple discharge is rare, constituting only 3-5% of mammary consultation. In the present paper 267 patients with primary nipple discharge operated on at Institut Gustave-Roussay (IGR) in Villejuif, France, between January 1, 1960 and December, 1974 were evaluated. In all cases, the nipple discharge was symptomatic, spontaneous, and represented the primary reason for the patient's consultation. During the same period 1,145 cases of nipple discharge were treated at IGR. Of the 1,145 cases with symptomatic nipple discharge, 267 patients (23%) required surgical intervention. Among these, fibrocystic disease and duct ectasia were the leading causes of nipple discharge occurring in 42% of surgical specimens. Twenty one per cent of the patients had carcinoma and 35% were found to have intraductal papilloma. The overall incidence of malignancy, however, was 4.8% among the 1,145 women with nipple discharge. On the average, patients with nipple discharge due to malignancy were ten years older than those with benign lesions (Table 2). Approximately 25% of patients with malignant discharge and 5% with benign discharge have associated tumor. Over 60% of the patients with both discharge and a mass had malignancy.

Between June 1970 and April 1982, 592 patients with unilateral T1 and small T2 breast cancers were managed conservatively at the Institut Gustave-Roussy. The treatment policy for the axilla was to perform a lower axillary dissection and to proceed to axillary clearance ( +/- radiotherapy) in patients with axillary invasion by tumor (N+). Some N+ patients had only lower axillary dissection and radiotherapy. Five hundred fifty-eight patients underwent axillary surgery which was a lower axillary dissection in 374 patients (67%) and axillary clearance in 184 patients (33%). There was axillary invasion in 198 cases (36%). Only five patients relapsed in the axilla and the probability of axillary relapse at 5 years was 1.2%. There were no axillary relapses in N+ patients who had had an axillary clearance whether irradiated or not. The incidence of upper limb complications was significantly greater in patients undergoing axillary surgery and radiotherapy compared with axillary surgery alone (p less than 0.0001). It is concluded that a lower axillary dissection accurately identifies N-patients and an axillary clearance in N+ patients ensures good local control and avoids the morbidity associated with axillary irradiation.

From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).

In a series of 94 human mammary carcinomas, the determination of total estrogen (ER) and progesterone (PR) receptors by a single saturating dose method (5 nM for ER, 10 nM for PR) using dextran-coated charcoal was compared to an immunohistochemical method utilizing ER monoclonal antibody (ER-ICA test). There was a good correlation expressed in positive terms between the ER-ICA test and the biochemical determination of ER (94% of concordance) with a statistical value of P less than 0.01 being found between the concentration of ER (biochemical) and the percentage of labeled cells (ER-ICA). The ER-ICA test complements the ER and PR (biochemical) and is particularly useful for ER determinations on small tumor specimens as no additional tissue other than that from the biopsy is required.

The extent of osteogenic sarcoma has been measured in 30 bones obtained after local resection and compared with pre-operative evaluation. In only one case was the articular cartilage involved and the whole joint was resected. Other cases with a metaphyseal localisation were treated by disarticulation. Articular cartilage appears to provide good protection against local extension. In contrast, the growth cartilage, which was present in 11 cases, was crossed by tumour on three occasions. In only one case of diaphyseal localisation was a resection made across the tumour which had been previously rendered necrotic by chemotherapy. In most of the diaphyseal localisations, the post-operative study revealed that the resection had been over-extensive. Tomodensitometry is not very reliable in the precise evaluation of the extent of diaphyseal involvement.

The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.

We report 7 cases of unusual fibroadenomas of the breast. They are characterized by an exuberant cellular proliferation within the ductal lumens. They appear in young women from 20 to 40 years old. These lesions are histologically identical to those described by Azzopardi (1979) under the name of "Argyrophilic cells in fibroadenomas" and by Eusebi and Azzopardi (1980) and by Govoni (1981) and called "Lobular endocrine neoplasia in fibroadenoma of the Breast". An immunohistochemical study reveals a major positivity of these cells, in all cases, with Antikeratin Antibody (anti Kl1) and with Epithelial Membrane Antigen (anti EMA) proving the epithelial origin of these cells. There cells cannot yet be regarded as belonging to the neuro-endocrine group, because of the negativity, in all cases of Grimelius and Bodian stains, and of the very heterogeneous positivity observed with Neuron-Specific Enolase antibody (anti NSE) and with anti Human Natural Killer antibody (anti HNK). These cellular proliferations seem to us, on the microscopical point of view related to the atypical epithelial hyperplasias of the breast, and different from the in situ lobular carcinoma. Thus we propose to call these lesions "variant of the breast fibroadenoma" characterized by an atypical epithelial clear cell hyperplasia. The treatment of these lesions merely consists of a lumpectomy. Only one case is associated with an eleven years free of disease follow-up: a follow-up comprised between on to fifteen months is observed in the others cases. The knowledge of these benign lesions appears to us very important, to avoid improper treatment caused by an erroneous diagnosis of carcinoma developing in a breast fibroadenoma.

We have previously described a secreted glycoprotein of mol. wt 52,000 (52-kDa protein) which is induced by estrogen in some human breast cancer cell lines. This protein has been identified as the proenzyme of a lysosomal cathepsin-D-like protease which is secreted in large proportions in breast cancer cells. To determine which information may be generated by this marker when detected in mammary tumors, in comparison with hormone receptors, we used monoclonal antibodies interacting specifically with the 52-kDa protein and its related cellular processed products (mols. wts 48 and 34 kDa). A high concentration of this protein has been shown in proliferative ductal mastopathies and cysts, suggesting its value in detecting high-risk mastopathies. We now present the immunoperoxidase distribution of this protein in breast carcinoma compared to the cytosolic hormone receptors assayed in parallel. In 232 breast cancers, no correlation was found between the cellular 52-kDa protein content and cytosolic estrogen or progesterone receptor concentrations. This absence of correlation was also shown by the constitutive production of this protein by estrogen-receptor-negative breast cancer cell lines and confirmed by double immunostaining of breast cancer cell aspirates showing a dissociation between the cytoplasmic staining of this 52-kDa lysosomal protease and the nuclear staining of the estrogen receptor. These clinical results, associated with the in vitro mitogenic and proteolytic activities of this protein, strongly suggest that the 52-kDa protein staining in tissue is associated with tumor proliferation and/or invasion, rather than with hormone responsiveness.