A. Avril

The prognostic value of c-erbB2 in primary breast carcinomas: A study on 942 cases

SummaryTo assess the practical prognostic value of c-erbB2, we performed a study on 942 invasive ductal carcinomas treated with primary surgery between 1980 and 1986 in our center. We evaluated its expression by immunohistochemistry in paraffin-embedded tissue using a polyclonal antipeptide antibody. Of 942 tumors, 229 (24%) showed a positive membrane staining. We observed a significant association between c-erbB2 and Scarff-Bloom-Richardson grading (p < 0.0001) and a negative correlation between c-erbB2 and both estrogen and progesterone receptors (p < 0.0001). In our analysis, with respect to overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS), c-erbB2 was statistically significant (p ≤ 0.0001) for the whole group and the node-positive subgroup. In multivariate analysis, c-erbB2 appeared to be an independant variable for RFS and MFS in the node-negative group. However, in our hands, c-erbB2 had a poor prognostic value in comparison with the classical prognostic variables such as histological grade, nodal status (N), hormonal receptor status (estrogen and progesterone receptors), and tumor size, and it did not supersede the classical parameters.

A critical analysis of treatment strategies in desmoid tumours: a review of a series of 106 cases

BACKGROUND The management of desmoid tumours, previously based on strategies employed for sarcomas, should be reassessed, given the morbidity of interventions used in their treatment. METHODS Long-term follow-up (median 123 months) of a series of 106 treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome. RESULTS Desmoids typically evolved actively over a median period of 3 years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17 months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy. CONCLUSION Desmoids are relatively indolent tumours needing different approaches than sarcomas. Direct surgery is advisable only in primary lower trunk wall/girdle locations. Wait-and-see and medical treatment is preferable in other types of presentations.

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T2>3 cm and T3 N0–1 M0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIα. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIα expression and tumour chemosensitivity and thus may have important practical implications.

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers

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 5 microns 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 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 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.

Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases.

SummaryP53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed.Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status.Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status, and tumor size.

Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast

To evaluate the prognostic relevance of Ki‐67 and topoisomerase IIα expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki‐S11 (Ki‐67) and Ki‐S4 (topoisomerase IIα). pS2, c‐erbB2, and p53 were additionally considered as prognostic variables. The median follow‐up time was 149 months. Eight‐hundred‐and‐sixty‐three tumors reacted with Ki‐S11 and Ki‐S the labeling indices of the two antigens were closely associated (r=0.93). Both correlated positively with the tumor size, c‐erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki‐S11 and Ki‐S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis‐free survival (p <0.00001). Estrogen receptor status, p53, and c‐erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki‐S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki‐S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki‐S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIα expression as assessed by monoclonal antibody Ki‐S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.

Application of the Van Nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examinated by serial macroscopic sectioning: Practical considerations

The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2 mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p=0.001), with reduction of distance to margins (p=0.05), with histologic grade (p=0.02), with percentage of positive blocks (p=0.0003) and with VNPI score (p=0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p=0.0001).Conclusion: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.

Retroperitoneal soft tissue sarcomas: A pilot study of intraoperative radiation therapy

This pilot study was conducted to evaluate the feasibility and tolerance of a multimodal therapy of retroperitoneal soft tissue sarcoma (STS), including intraoperative radiation therapy (IORT). Nineteen patients (14 primarily treated patients and 5 treated for a recurrent tumor) were included. Surgery included a complete resection (14), a partial resection (2), and no resection (2). The median IORT dose was 17 Gy. Thirteen patients also received an external radiation therapy (ERT). Nine patients received chemotherapy. There was no postoperative mortality. Immediate postoperative complications occurred in four patients (21%). Delayed complications occurred in six patients, including one lethal iliac artery disruption. With a median follow‐up of 17 months, the 2‐year disease‐free survival rate was 60%, and the 2‐year actuarial local control rate was 76%. A multimodality approach of treatment, including IORT and ERT and eventually chemotherapy, appears feasible in patients with retroperitoneal STS. However, the treatment‐related morbidity appeared relatively high in this study.

Immunohistochemical determination of pS2 in invasive breast carcinomas: A study on 942 cases

SummaryTo assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.

Breast cancer and in vitro fertilization. About 32 cases.

Because of the increased risk of breast cancer for infertile nulliparous women, the suspected promoter role of estradiol in mammary carcinogenesis and the high frequency of ovulation inducer treatments, it was interesting to focus on the risk of breast cancer after such a treatment. We reviewed 32 cases during a retrospective survey in Assisted Reproductive Techniques (ART) centers in France. Because of the small sample size and the few cases published so far, no statistical study could be made. However, many observations may have gone unnoticed or were not published. Two hypotheses can be proposed: (1) the facilitating role of stimulation on potential infra-clinical or un-diagnosed cancers; (2) the initiation of new cancers. Consequently, we propose to establish a register for the follow-up of treated women to monitor the advent of new cancers and to increase the follow-up of patients with other associated risk factors.