G. MacGrogan

Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi

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.

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>3u2009cm 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 40u2009mm (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 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>3u2009cm 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 40u2009mm (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.

Lymph node involvement in epithelial ovarian cancer: sites and risk factors in a series of 355 patients.

Objectives: To perform a cartography of lymph node metastases in epithelial ovarian cancer and to determine predictive factors of lymph node metastases. Method: The charts of 355 patients with epithelial ovarian cancer who underwent lymphadenectomy during a primary (n = 252) or secondary debulking surgery (n = 103) were analyzed. The topography of the lymph node metastases was notified for the whole group according to the stage of the disease, the histological type, and the moment of surgery. In patients who underwent a primary surgery before chemotherapy, independent prognostic variables for the risk of lymph node involvement were tested with a multivariate analysis. Independent prognostic factors were combined to determine risk profiles in individual patients. Results: The main area of the lymph node metastases was para-aortic. Isolated pelvic lymph node involvement was 10%. Three variables independently predicted lymph node invasion: advanced T stage, high-risk histological profile, and metastases. Conclusions: When lymphadenectomy is recommended, systematic lymph node dissections in the aortic and pelvic areas are warranted. An isolated pelvic lymph node assessment, particularly in the early stages, is inappropriate. By combining independent risk factors, a useful tool for individual risk assessment of lymph node involvement could be established, helping to decide whether to perform a lymph node dissection, especially at restaging surgery.

Prise en charge des atypies épithéliales du sein

Resume En attendant une classification moleculaire des atypies epitheliales du sein, les auteurs font une mise au point sur leur prise en charge, a la lumiere des travaux de la litterature et de leur experience a l’institut Bergonie. Leur experience repose sur l’analyse de 2 833 biopsies chirurgicales effectuees pour micro-calcifications sans tumeur palpable, etudiees en coupes macroscopiquement seriees (26 blocs en moyenne par biopsie) chez des patientes avec un long suivi median (160 mois). Cette mise au point concerne l’application de la classification OMS des lesions proliferantes atypiques non invasives du sein, la mesure des hyperplasies canalaires atypiques, la prise en charge des patientes avec des atypies epitheliales diagnostiquees sur microbiopsies, et enfin l’examen des biopsies chirurgicales de re-excision a la recherche d’un petit cancer concomitant de voisinage associe, retrouve dans un tiers des cas environ. En effet, il semblerait que les atypies epitheliales soient davantage un marqueur de risque de cancer concomitant que de cancer secondaire.

Identification en pratique clinique des carcinomes basal-like du sein : des carcinomes « triple zéro/BRCA1-like »

Basal-like carcinomas represent 10 to 15% of invasive breast carcinomas and have been identified from gene expression studies. Morphologically, these tumors are undifferentiated histopronostic grade 3 carcinomas, identified in clinical practice according to their immunophenotype triple zero (estrogen, progesterone and ERBB2 negative) associated with the high molecular weight cytokeratins 5/6/14 and/or EGFR expression. At the molecular level, these tumors harbour nearly 100% P53 mutations, a high rate of PTEN mutations with an AKT pathways activation and numerous chromosomal alterations such as gains and losses. They share a high degree of similarity at the morphological, phenotypical and molecular level with BRCA1 tumors that justify the proposal of a different name such as triple zero/BRCA1 like carcinomas for sporadic basal-like carcinomas. Indeed, the current basal-like name could suggest a myoepithelial cellular origin of such lesions. Furthermore, tumors with such a basal-like immunophenotype constitute a heterogeneous group of tumors encompassing good prognosis tumors such as adenoid cystic and juvenile secretory carcinomas. There is an urgent need for more specific therapies for basal-like/triple zero/BRCA1-like tumors. Therapeutic progresses rely on a better understanding of the molecular alterations that occur in these tumors and the BRCA1 tumors. Indeed, recent clinical trials with PARP inhibitors for basal-like/BRCA1 like tumors should improve the prognosis of these patients and are a direct benefit of a better understanding of the molecular biology of these tumors.

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

OBJECTIVEnTo 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).nnnPATIENTS AND METHODSnRetrospective 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.nnnRESULTSnThe 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).nnnCONCLUSIONnCareful 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

Neoadjuvant endocrine treatment in breast cancer: analysis of daily practice in large cancer center to facilitate decision making

BACKGROUNDnTo examine outcomes of neoadjuvant endocrine therapy in daily practice to inform decision making.nnnMETHODSnWe retrospectively selected 204 patients who received neoadjuvant endocrine therapy with T2 (≥30 mm) or T3 tumors, examining subsequent breast-sparing surgery and long-term outcomes.nnnRESULTSnNeoadjuvant endocrine therapy was administered for 7.3 months (median) and breast-sparing surgery was achievable in 53% of patients. Smaller initial tumor size and modified version of the Scarff-Bloom and Richardson grades 1 to 2 were associated with breast-sparing surgery. Disease progression during treatment was 6.9%; actuarial risk of local relapse was 3% at 5 years and 15% at 10 years. Five- and 10-year metastasis relapse-free survival was 78% and 63%, respectively. Grade 3, negative progesterone receptors, and absence or slow response to neoadjuvant therapy were associated prognostic factors.nnnCONCLUSIONnThese daily practice data provide important information about feasibility, efficacy, and long-term results of neoadjuvant endocrine therapy and can be used to inform patients for decision making between mastectomy and endocrine induction therapy.