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This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5μm thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P=6.3×10−5) and histologic grade (P=4.9×10−7). Statistically significant correlations were found with OS (P=4.6×10−5) and MFI (P=6.4×10−9). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P=7.7×10−7) before tumour size and grade, and was second after tumour grade for OS (P=0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

Metastases to axillary lymph nodes is an important factor in predicting prognosis and survival in primary operable carcinoma of the breast. A series of post mastectomy lymph nodes (150 cases) was selected in this retrospective study, in which the initial diagnosis had been no metastases by light microscopy and in which a long follow-up was available (average 10 years). The original H&E sections from these cases were immunostained to detect metastases which might not have been previously appreciated. The study was performed using a cocktail of 5 monoclonal antibodies directed against epithelial antigens. The object was to explore the possibility of detection of occult micrometastases by immunohistochemistry and to evaluate their prognostic significance. Micrometastases with individual cells and cell clusters were readily detected by this technique in 14% of all cases. It also became apparent towards the end of the study that micrometastases could be detected with equal sensitivity by any one of the 5 monoclonal antibodies. Positive staining of malignant cells was found to be more frequent in invasive lobular carcinoma (ILC) than in invasive ductal carcinoma (IDC). However, for the IDC group a striking association was found between micrometastases and both recurrence and survival rate. The ILC sample was considered too small for meaningful interpretation. We recommend the use of immunohistochemical techniques using monoclonal antibodies for the detection of occult metastases in lymph nodes to improve the prediction of recurrence and survival in invasive ductal carcinoma of the breast.

From 1972 to 1976, 95 patients with clinical stages I-IIIA Hodgkin's disease were treated by chemotherapy with cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP) before and after extended field radiotherapy. The CVPP schedule gave: (1) a constant drug dosage for each patient independent of body surface or weight; and (2) a total drug dosage dependent on haematological tolerance, since the treatment was given for 21 days or until the leukocyte count dropped to 2 x 10(9) l-1. The drug dosage per unit body surface (or 'dose density') significantly correlates with the drop in leukocyte count (P less than 0.001) and the tumour regression at the end of the induction course (P = 0.020). Disease-free survival is significantly related to dose density (P = 0.050) but not to dose intensity calculated on the duration of treatment (P = 0.240). However, after exclusion of three marginal recurrences due to border-line radiotherapy, the dose intensity significantly correlates with the disease-free survival (P = 0.031) and with the duration of complete remission (r = 0.870).

Fourty-one patients underwent breast reconstruction after mastectomy for cancer and reduction plasty of the second breast, over a 36-month period. These plasties were performed only for reasons of asymmetry, in the absence of any positive preoperative finding. Histologic examination using semiserial sectioning of the whole excised sample detected a high frequency of unsuspected cancer 14/41 (34%). There was a strong predominance of in situ carcinomas 11/41 (27%) over invasive carcinomas 3/41 (7%). These results were compared with those of other bilateral cancer series. When such cancers were detected by random biopsies or mastectomies, the rate of in situ carcinomas was much greater than in cancers detected only by physical and mammographic examination.

From 1980 to 1984, we observed 144 undifferentiated cancers, of which 116 (0.9% of all cancers treated during this period) were treated in our center. Immunohistochemical study classified 130 tumors (90%), which comprised 82 non-Hodgkin's lymphomas (57%), 32 carcinomas (22%), 7 melanomas (5%), 7 sarcomas (5%) and 2 others (1%). Sixty-nine patients, with the diagnostic problem of non-Hodgkin's lymphoma versus carcinoma, which was solved by immunohistology, were followed up for 44 ± 20 months. Lymphomas (57 cases) had a better clinical course than carcinomas (11 cases), and a clinical course similar to high-grade lymphomas identified by conventional histology. For 66 patients with the same problem, the treatment was started before the immunohistochemical diagnosis. This treatment was inappropriate in the light of the correct diagnosis in 16 of 66 cases (24% of all cases).

Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mib1 (antiKi-67), pS2, GST pi, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P = 0.001). A high percentage of Mib1-positive tumour cells (> 40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P = 0.009 and P = 0.03). By multivariate analysis IHC-ER, Mib1 and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P = 0.0006), disease-free interval (DFI) (P = 0.03) and metastasis-free interval (MFI) (P = 0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.

Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node-negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH micrometastases had no prognostic value (median follow-up: 9.3 years). In the IDC group, IH micrometastases were correlated with recurrences (P = 0.01) and were the most significant predicting factor, but were less correlated with survival (median follow-up: 15.6 years). Three main points emerge from this study: (1) SMS micrometastases have a prognostic significance and macroscopic sectioning is recommended as a routine technique not requiring excessive work. (2) IH micrometastases in infiltrating lobular carcinoma have no prognostic significance. (3) The value of IH is debatable in infiltrating ductal carcinoma, since the technique is of principal use in predicting recurrences. It should therefore be carefully assessed vs other prognostic factors currently under study.