V. Picot

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.

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.

Prognostic significance of immunohistochemically detected breast cancer node metastases in 218 patients

Axillary lymph node metastases detected by immunohistochemistry in standard node-negative patients with breast carcinomas (13 out of 129 infiltrating ductal carcinomas and 37 out of 89 infiltrating lobular carcinomas) do not have any prognostic significance in patients followed up for a long time (respectively 24 and 18 years). Moreover, their pejorative significance in the literature is debatable since the groups and events taken into account are heterogeneous.

DNA topoisomerase IIα expression and the response toprimary 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.

Immunohistochemically detected lymph node metastases from breast carcinoma: practical considerations about the new American Joint Committee on Cancer classification.

The authors applied the sixth edition of the American Joint Committee on Cancer (AJCC) classification system to their previously published group of patients with breast carcinoma who had immunohistochemically detected lymph node metastases.

Sarcomes primitifs du sein: À propos d’une série rétrospective de 42 cas traités à l’Institut Bergonié sur une période de 32 ans

OBJECTIVE To evaluate the experience of a single cancer center with unusual tumors. To analyze Primary breast sarcomas (PBS). To investigate treatment and prognostic factors influencing overall survival (OS) and disease-free survival (DFS). PATIENTS AND METHODS Retrospective study of a series of 42 patients. We reviewed the clinical records and pathology slides of 42 women with PBS treated in our institution between 1970 and 2002. Log-rank tests were used to determine OS and DFS. RESULTS The median age at diagnosis was 56.9 years (24-81 years). Surgery was part of the therapeutic strategy in all the patients. Patients with angiosarcoma and those with malignant cystosarcoma constituted distinct populations. The 10-year OS and DFS rates were 53% and 55% for angiosarcoma patients and 89% and 100% for cystosarcoma patients (p=0.009 and 0.01 respectively). CONCLUSION Careful preoperative multidisciplinary assessment is required before making the decision to treat. Mastectomy is generally indicated. Axillary lymph node dissection is not indicated.Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 33 - N° 7 - p. 589-599

Quality of life in patients with aggressive non-Hodgkin's lymphoma. Validation of the medical outcomes study short form 20 and the Rotterdam symptom checklist in older patients

In the elderly population, cancer treatment aims to cure and/or maintain Quality of Life (QoL). However, there is little QoL data to provide evidence for QoL benefits for some of the cancer treatments. This pilot study developed valid QoL questionnaires in French, for patients over 65 years with a diagnosis of large cell lymphoma, part of the Lymâge phase II study. They were asked to complete two questionnaires, the Medical Outcomes Study Short Form 20 (MOS SF20; generic) and the Rotterdam symptom checklist (RSCL; cancer-specific). Between June 1995 and April 1997, questionnaires were returned by 63 of 89 patients. This article reports the process undertaken to adapt the English version to a French setting, and provides the results of factor analysis, convergent and discriminant validity and reliability. Our data suggest that QoL questionnaires can be used in elderly patients. These two questionnaires are validated in French and would help us to analyse the QoL of elderly patients with the development of new treatments as done in the Lymâge study.