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Summary The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer are well established. For many years, five years’ treatment with tamoxifen was the gold standard of adjuvant treatment. The recent development of new endocrine agents provides physicians with the opportunity to take a more effective therapeutic approach. Nevertheless, the success of neoadjuvant endocrine therapy is much more recent and less frequently reported in the literature. This article reviews the studies published on neoadjuvant endocrine treatment (tamoxifen and aromatase inhibitors). According to the literature, neoadjuvant endocrine therapy seems to be effective and well tolerated. The newer generation of aromatase inhibitors (letrozole, anastrozole, exemestane) appear to result in better overall response rates and more conservative surgery than tamoxifen. Patients with an ER Allred score of 6 and over are most likely to respond and gain clinical benefit. The optimal duration of neoadjuvant therapy has not yet been investigated in detail. These preliminary results are interesting and should be confirmed by further studies.

Resume Objectif Preciser le role du curage ganglionnaire axillaire dans les carcinomes canalaires in situ micro-invasifs (CCIS-MI) du sein a partir d’une serie de 107 cas consecutifs. Methodes Travail anatomoclinique retrospectif monocentrique avec application des recommandations europeennes en adoptant comme definition pathologique la presence de foyer(s) de micro-invasion n’excedant pas 1 mm. Le curage axillaire etait systematiquement complet ; il a ete precede chez 10 malades par la recherche du ganglion sentinelle par methode isotopique. Resultats L’envahissement ganglionnaire a ete mis en evidence dans 8 cas sur l’ensemble de l’effectif (7,5 %) ; tous les cas, sauf un, comportaient des caracteristiques histologiques pejoratives communes : sous-type architectural comedo, haut grade nucleaire, taille lesionnelle > 3 cm. Le taux d’envahissement ganglionnaire atteignait 18,5 % dans le sous-groupe des comedocarcinomes micro-invasifs de haut grade mesurant plus de 3 cm. Conclusion Contrairement aux CCIS purs, les CCIS-MI necessitent une exploration chirurgicale de l’aisselle dont les modalites les mieux appropriees sont aujourd’hui discutees : curage ganglionnaire axillaire classique ou recherche du ganglion sentinelle, ce procede d’adenectomie selective n’etant pas encore une technique consensuellement validee.

Resume Etude retrospective (1985–1998) portant sur les caracteristiques operatoires et anatomopathologiques de 155 cancers infracliniques du sein reveles par une opacite stellaire. Materiels et methodes – Les mammographies provenaient du depistage individuel ou organise. L’âge moyen etait de 58,5 ans (44–78), 129 patientes etaient menopausees (83 %). Le reperage preoperatoire etait stereotaxique dans 57 cas (36,5 %), echographique dans 98 cas (63,5 %). Le diametre lesionnel etait 97 fois inferieur ou egal a 10 mm dont 15 inferieur ou egal a 5mm, moyenne : 11 mm (extremes : 4–25). Le curage axillaire a ete realise 147 fois immediatement (95 %), huit fois secondairement (5 %). Resultats – Les cancers infracliniques du sein donnant une image stellaire correspondaient a des cancers infiltrants : canalaires (CCI) dans 130 cas (84 %), lobulaires (CLI) dans 25 cas (16 %). Aucun cancer canalaire in situ (CCIS) n’a ete revele ainsi. Le grade SBR a ete formule pour les CCI : 95 grade I (73 %), 31 grade II (24 %) et quatre grade III (3 %). Les recepteurs hormonaux ont ete doses sur 145 pieces : recepteurs œstrogeniques et progesteroniques etaient tous les deux positifs dans 125 cas (86 %). Un envahissement ganglionnaire (N+) a ete retrouve dans dix cas (6 %), tous CCI superieurs ou egaux a 5 mm. Cent cinquante traitements conservateurs (97 %) ont ete effectues. Commentaires – Les cancers stellaires sont generalement infiltrants de type canalaire mais aussi lobulaire. Ils se distinguent donc des cancers reveles par des microcalcifications, essentiellement de type canalaire dans leurs formes infiltrantes mais aussi in situ (CCIS). Dans cette serie, les cancers stellaires reunissaient des criteres histologiques et biologiques favorables : differenciation et hormonodependance frequente (trois fois sur quatre), N+ exceptionnel.

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).

126 patients with non-inflammatory operable breast cancer, who otherwise would have undergone modified radical mastectomy (MRM), were treated by induction chemotherapy. Before treatment, every patient had a local and general assessment, and pathological or cytological evidence of malignancy. Patients received, every 3 weeks, the same treatment with doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil (AVCF); methotrexate was added in 80 cases (AVCFM). Tumour shrinkage greater than 50% was documented in 105 (83%) of the 126 women. A higher objective response rate was obtained in aneuploid or high S phase tumours, especially in the patients treated with methotrexate. After chemotherapy, 41 patients were then treated by radiotherapy alone after complete or sub-complete response; 64 had a residual tumour that could be treated by conservative surgery and radiotherapy. Only 19 had MRM and radiotherapy. Histopathological complete remission was documented in 1 case; isolated residual tumour cells were found in 5 patients. Thus primary chemotherapy enhanced the possibility of breast conservation in up to 83% of the cases in a series in which most would have been otherwise subjected to a MRM because of tumour size.

Specify the role of axillary lymph node removal in micro-invasive in situ duct carcinomas (DCIS-MI) of the breast with a series of 107 consecutive cases.Single-centre, retrospective, anatomoclinical study with application of the European guidelines adopting as pathological definition the presence of areas of micro-invasion not exceeding 1mm. Axillary lymph node dissection was systematically complete and was preceded by the search for the sentinel node in 10 patients using the isotope method.Lymph node invasion was revealed in 8 cases in the global population (7.5%). All the cases except one exhibited typical deleterious histological features: comedo architectural sub-type, high nuclear grade, and size of the lesion3 cm. The lymph node invasion was of 18.5% in the sub-group of high-grade micro-invasive comedo-carcinomas measuring more than 3 cm.Contrary to those exhibiting pure DCIS, DCIS-MI patients require surgical exploration of the armpit, the most appropriate modalities of which are currently debated: classical axillary lymph node dissection or search for the sentinel lymph node; the selective lymphadenectomy procedure is not yet a consensually validated technique.

This study investigated the efficacy and tolerability of FEC 100 (epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2) every 21 days as neoadjuvant chemotherapy in women with stage I-III primary operable breast cancer. Forty patients were treated with 6 cycles of FEC 100, followed by surgery and radiation therapy. In addition, most patients also received an adjuvant treatment for residual disease (11 chemotherapies and 31 tamoxifen). After 6 cycles of FEC 100, the overall clinical response rate of 75% (CI 95%, 61.6-88.4) was achieved, 22.5% of which were complete responses. Breast conservation was achieved in 70% of patients. A pathologic complete response was confirmed in 6 patients (15%; CI 95%, 3.9-26.1) using Chevallier's classification and in 10 patients (25%; CI 95%, 11.6-38.4) using Sataloff's classification. After a median follow-up of 29.5 months, 3 metastatic relapses were observed. The principal toxicity of FEC 100 was myelosuppression; 51.3% of patients developed grade 3/4 neutropenia. Neoadjuvant FEC 100 was both effective and well tolerated in patients with early-stage operable breast cancer.

Various alterations of aminoacidemia have been described during breast cancer. The aim of this study was first to establish the specific modifications of plasma-free amino acid concentrations by a comparative study of 19 patients with mammary tumors and 18 healthy volunteers, and, second, to determine the evolution of aminoacidemia after surgical tumor removal. Aminoacidemia was determined the day before (D0), and then five days, one month (M1), and six months after surgical removal of the tumor, and a single determination was performed in control subjects. Plasma levels (mumol/L) of serine and glutamate were higher in cancer-bearing women at D0 (respectively, 124 +/- 3 and 68 +/- 7) than in healthy volunteers (respectively, 110 +/- 6 and 48 +/- 5). Surgical tumor removal induced a normalization of aminoacidemia (in mumol/L at D5: serine: 114 +/- 4; at M1: glutamate: 55 +/- 6 Non Significant (NS) from values of healthy subjects). Among the various patterns reported for breast cancer, we confirm one of those described by Cascino in 1995, and we show that these levels revert to normal after tumor surgical removal.

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p

The purpose of this retrospective study was to evaluate the influence of axillary disease on patients' survival after neoadjuvant chemotherapy and to assess patient and tumor characteristics associated with post-chemotherapy axillary involvement. After six induction cycles, 277 patients with operable breast cancer (stage II-III) underwent surgery with axillary dissection, followed by radiotherapy (n = 267) or additional chemotherapy (n = 63) and adjuvant tamoxifen therapy (n = 138). At a median follow-up of 8.5 years, overall survival (OS) and disease-free survival (DFS) were analyzed as a function of node involvement. The differences in OS and DFS according to the number of positive nodes were highly statistically significant with a decreased survival associated with the increasing number of nodes (p = 5 x 10(-6) and 9 x 10(-7), respectively). Upon multivariate analysis, the node number after chemotherapy appeared as the most significant prognostic factor (p = 7 x 10(-4) for OS and p = 3 x 10(-5) for DFS). All the other classical prognostic factors were insignificant, except post-chemotherapy Scarff-Bloom-Richardson (SBR) grading for OS (p = 8 x 10(-4)) and adjuvant hormonotherapy for DFS (p = 1 x 10(-2)). Although constituting a different parameter from primary surgery data, the number of positive nodes after chemotherapy could still remain a valuable prognostic factor at secondary surgery, raising the question for high risk patients of a second non-cross-resistant adjuvant regimen, or high dose chemotherapy with peripheral blood stem cells support.

Purpose. In order to improve the breast conservation rate for noninflammatory operable breast cancer stage II and IIIa, neoadjuvant chemotherapy containing vinorelbine, 25 mg/m2, epirubicin, 35 mg/m2, and methotrexate, 20 mg/m2, VEM, was administered days 1 and 8 every 28 days for six cycles. Methods. From October, 1991 to April, 1996, 89 patients (median age 52 years, range 31-72; 68 stage II and 19 stage IIIa) received 519 cycles (median six) of VEM chemotherapy. Results. Hematotoxicity was mild (World Health Organization grade 3-4 neutropenia in 28% of cycles for 22 patients, and anemia or thrombocytopenia >grade 2) when it occurred, and there were no toxic deaths. The clinical objective response was 90% (28% complete response and 62% partial response). All patients underwent surgery: 77 (87%) had conservative and 12 (13%) had modified radical mastectomy, and 12 (14%) reached pathological complete response. At December, 2000, with a median follow-up of 86 months (39-100), 13 patients had relapsed, and five had died of metastatic disease. Median disease-free survival was 100 months (8.4 years) and median survival had not yet been reached.

O 6 -Methylguanine-DNA methyl transferase (MGMT) in human carcinomas has been associated with tumor resistance to alkylating agents. The aims of this study were: i) to correlate tumor MGMT expression and patient and tumor characteristics in malignant breast carcinomas treated with induction chemotherapy including cyclophosphamide (CPM) and ii) to study the predictive and prognostic values of tumor MGMT gene expression. We used RT-PCR to measure the levels of tumor MGMT expression in 107 patients with breast carcinomas prior to neoadjuvant chemotherapy. Sixty patients (56%) received anthracyclines and CPM and 47 (44%) received only anthracyclines. Low levels of MGMT expression correlated with Scarff-Bloom-Richardson grade III (p

The Scarff-Bloom-Richardson (SBR) grade, an important prognostic factor in breast cancer, was also associated with cell proliferation, a consistent indicator of response to chemotherapy. The determination of an association between SBR grade and responsiveness would be clinically useful. We explored the influence of SBR grade on response to neoadjuvant chemotherapy in patients with invasive ductal breast carcinoma. The present study centered on 431 patients registered onto one of four prospective phase II trials. SBR grading was performed according to the Elston method on needle core biopsies prospectively collected prior to treatment from 290 patients and on residual tumour at surgery from 171 patients. The post-operative grades were then compared with those obtained at diagnosis. Univariate and multivariate analysis were used to evaluate the significance of SBR grade on response to neoadjuvant chemotherapy. Both statistical analysis revealed that SBR grade III tumours responded better to neoadjuvant treatment than SBR grade I (p

Subclinical mammographic abnormalities discovered through screening are subjected to excisional surgical biopsy in order to prove or rule out malignant disease of the breast by histological examination. Close attention should be paid by the surgeon to avoid cosmetically disfiguring scar and failure in excision removal exhibited on postoperative mammogram. Indications for surgical assessment are selected upon suspicious patterns of opacities, clusters of microcalcifications or architectural distortions. Good communication between the radiologist, the surgeon and the pathologist is required for proper management of non palpable lesion. The most adequate lumpectomy technique should be performed with regard to the oncologic risk and cosmetic outcome.

Overcoming the drawbacks of X-ray mammography and magnetic resonance imaging (MRI) by fusing the information in order to assist clinicians in the task of early detection of breast cancer in women with dense breasts. A detailed 3D computer-generated breast phantom based on empirical data extracted from breast MRI was constructed for each patient. To achieve this goal, MRI data were classified into the different components of breast tissue (glandular, adipose, skin and eventually tumor) using a semi-automated segmentation algorithm based on voxel intensity. Then, a geometrical model of the breast was constructed through the isosurfaces of this segmented volume. In order to perform a study on breast deformation using the finite element method, the geometrical model was automatically meshed into tetrahedral elements and material properties were assigned to the different kinds of breast tissues. To represent the large deformation of breast during a mammography exam, a linear elastic model was chosen to describe the constitutive relations of breast tissues, and the compression was simulated using a stiff plate model. After compressing the phantom, mammograms were simulated based on the deformed configuration. During this step, a parametric optimization of the model was conducted (mesh refinement, mechanical properties and friction coefficient). Small variations of the model parameters strongly influence the deformation and modify significantly the resultant simulated images. During the optimization process, both a better conservation of details and a convergence toward a distribution of components were observed for finer meshes, whereas the friction coefficient affects mostly the skin deformation. The phantom developed in this study allows the modeling of large deformations through the use of the finite element method, and also allows the simulation of mammographic images containing highresolution details. Moreover, this phantom combines flexibility and realism, and can be used for multimodality imaging research but also for clinical performance optimization.

Purpose: Overcoming the drawbacks of x‐ray mammography and magnetic resonance imaging (MRI) by fusing the information in order to assist clinicians in the task of early detection of breast cancer. Methods: A detailed 3D computer‐generated breast phantom based on empirical data extracted from breast MRI was constructed for each patient. To achieve this goal, MRI data were classified into the different components of breast tissues (glandular, adipose, skin and eventually tumor) using a semi‐automated segmentation algorithm based on voxel intensity. Then, a geometrical model of the breast was constructed through the isosurfaces of this segmented volume. In order to perform a study on breast deformation using the finite element method, the geometrical model was automatically meshed into tetrahedral elements and material properties were assigned to the different kinds of breast tissues. To represent the large deformation of breast during a mammography exam, a neo‐Hookean hyperelastic model was chosen to describe the constitutive relations of breast tissues, and the compression was simulated using a stiff plate model. After compressing the phantom, mammograms were simulated based on the deformed configuration. During this step, a parametric optimization of the model was conducted (mesh refinement, mechanical properties and friction coefficient). Results: Small variations of the model parameters strongly influence the deformation and modify significantly the resultant simulated images. During the optimization process, both a better conservation of details and a convergence toward a distribution of components were observed for finer meshes, whereas the friction coefficient affects mostly the skin deformation. Conclusion: The phantom developed in this study allows the modeling of large deformations through the use of the finite element method, and also allows the simulation of mammographic images containing high‐resolution details. Moreover, this phantom combines flexibility and realism, and can be used for multimodality imaging research but also for clinical performance optimization.

The study concerns 265 patients with axillary lymph node dissection for non-palpable breast cancer. The mammographically detected breast tumors were: 36 ductal carcinomas in situ (DCIS), 23 microinvasive carcinomas, 206 invasive carcinomas of which 179 were invasive ductal cancers (IDC), 25 invasive lobular cancers (ILC) and 2 mucinous invasive carcinomas. The histologic size of the invasive component wasor = 5 mm in 38 cases, 6-10 mm in 84 cases, 11-15 mm in 53 cases, 16-20 mm in 16 cases,20 mm in 15 cases. Axillary dissection was performed immediately during the initial surgical procedure in 209 patients (79%) or secondarily in 56 (21%) according to the results of intraoperative examination of surgical specimens on frozen sections. Axillary lymph node involvement was not found in DCIS, microinvasive carcinomas or invasive carcinomasor = 5 mm in size. Among all 206 invasive breast carcinomas, lymph node involvement was found in 7.8% (16/206) of cases. There were 9/84 (10.7%) in tumors10 mm, 7/122 (5.8%) in tumorsor = 10 mm. Thus, it is concluded that lymph node involvement is unlikely to be found in patients with non palpable breast cancers, specially those with carcinoma in situ, microinvasive breast tumors and invasive breast cancer with less than 5 mm maximum diameter size. Axillary dissection may be avoided in these patients. However, the use of new prognostic factors of lymph node involvement may help in the definition of patient group.

The aim of this study was to measure the accumulation of 99mTc-sestamibi in breast tumors and their axillary lymph nodes in patients undergoing scintimammography.Eighteen patients who were scheduled for breast surgery underwent scintimammography with 740 MBq of 99mTc-sestamibi on the day before the operation. The next morning, reinjection with 370 MBq was performed. Immediately after the surgical procedure, the 99mTc activity of the tumor samples and, when available, the related lymph nodes was measured in a gamma counter. The samples were weighed and prepared for histological analysis. The activity of each sample was normalized to the mean activity of normal tissue samples obtained from the same patient.Among the 198 samples analyzed, the relative uptake of sestamibi was increased in 111 containing normal lymph nodes (1.80+/-0.79 vs 1.00+/-0.22, p0.05), as well as in the seven containing invaded lymph nodes (2.01+/-0.83, p0.01) and more dramatically, in the 22 with a carcinoma (5.64+/-3.06, p0.001). In two patients with a benign lesion, both scintigraphy and counting demonstrated increased activity in the tumor. Four patients had negative scan results despite the presence of malignant tumor and a more than fourfold increase of sestamibi concentration in two of them.Technetium-99m-sestamibi concentrates strongly in breast carcinoma, sometimes even when the scan results appear normal, and mildly in lymph nodes, especially when invaded; it also concentrates in some benign tumors, possibly in relation to the presence of epithelial hyperplasia.

A series of 112 mastectomies with immediate breast reconstruction performed in women with invasive cancer of the breast were followed for a mean of 30 months to determine cancer outcome, morbidity and aesthetic results of the different surgical techniques. The patients were divided into 3 groups according to indications: 49 cases with local recurrence after conservative treatment; 37 cases of large or multifocal tumours operated after chemotherapy and radiotherapy; 26 cases after tentative conservative surgery with incomplete tumourectomy. A total of 98 patients (87.5%) were irradiated before mastectomy with immediate breast reconstruction. Twenty-eight simple implants, 50 musculocutaneous flaps using the latissimus dorsi with implant and 34 musculocutaneous flaps with the rectus abdominis. During follow-up 16 patients died and cancer relapsed in 13 surviving patients. Seven local recurrences were observed. In all cases of early relapse, which may have possibly been triggered by immediate breast reconstruction, the patients had very poor prognosis criteria. Surgery took longer for mastectomy with immediate breast reconstruction using the rectus abdominis flap and required transfusion in 88% of the cases. Combining all the techniques, 19% of the patients had postoperative complications and 25% late sequellae. The aesthetic results were considered as good immediately after surgery in 14% of the patients with a simple implant, in 45% of those with a latissimus dorsi flap and in 81% of those with a rectus abdominis flap. Second surgical procedures to improve the aspect were performed in half the patients with a simple implant giving 50% good results, in 40% of the patients with a latissimus dorsi flap giving 68% good results and in 12% of the patients with a rectus abdominis flap giving 84% good results. In this series, patient satisfaction was closely related to the aesthetic quality of the results. Integrated into a well-planned multidisciplinary protocol, mastectomy with immediate breast reconstruction does not appear to affect the cancer outcome. Immediate breast reconstruction is a complex procedure and requires experience in plastic surgery to reduce the number of complications and to improve aesthetic results. Reconstruction with a rectus abdominus flap appears as the superior technique.

The authors report their experience with immediate breast reconstruction following salvage mastectomy for local recurrence of invasive breast cancer after conservative treatment. From January 1987 to December 1992, among 91 immediate breast reconstructions, 41 were performed for this indication. The results and complications were analyzed for each of the three techniques used: simple prosthesis (n = 5), latissimus dorsi flap with prosthesis (n = 26), trans abdominalis musculocutaneous flap--TRAM flap (n = 10). Immediate flap reconstruction appears to be required in cases of either early or late local relapse since the skin has been irradiated and the mastectomy must be extensive. The transrectus abdominalis flap allows more extensive resection and gives better cosmetic results without the need for a prosthesis.

A recent phase II study [1] has shown a high response rate of 50 % with Vinorelbine in metastatic breast cancer. It seemed logical to combine this new compound with the well tolerated and effective drugs Epirubicine and Methotrexate (respective response rate of 45% and 20%). A weekly (day 1 & 8) administration of Vinorelbine was performed as proposed in the phase II study; Epirubicine and Methotrexate were also infused at day 1 and 8 to decrease toxicity. In metastatic relapse, our aim was to increase complete response rate (CR); and in Neo-Adjuvant situation, aims were to obtain maximal tumor’s reduction to avoid modified radical mastectomy (MRM) and increase of clinical and pathological response rates.

Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5-fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure.

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.

Neo-adjuvant chemotherapy has at least the same effect on systemic metastasis prevention than an adjuvant treatment with the same protocol ; with the great advantage of decreasing tumor and metastatic node size before surgery, resulting in a lower rate of total mastectomy.

In order to avoid modified radical mastectomy a neoadjuvant approach was adopted in our institute for non-inflammatory tumours. From 01/88 to 12/94,238 patients (pts) received as primary chemotherapy 3 different regimens (all doses mg/m 2 ): (l) AVCF/AVCFM, 126 pts (adriamycin 30, vincristine I dl, cyclophosphamide 300, fluorouracil 400 d2–d5 and methotrexate 20 d2 and 4, every 28 d); (2) NEM, 69 pts (navelbine 25, epirubicin 35, methotrexate 20 dl and d8, every 28 d) and (3) TNCF, 43 pts (THP-adria 20, dl–3, navelbine 25 dl and d4, cyclophoshamide 300, fluorouracile 400 dl–d4, every 21 d). In spite of good results with AVCF, the new combinations with navelbine seemed promising (NEM regimen concerned mainly stage II and TNCF stage III tumours): they were all operated for (2) and (3), partially for (l), and showed a progression in pathological complete response rate (pCR). Evaluation comprised 3 methods: clinical (C), echographic (E), mammographic (M). If breast conservation rate (85/85/77%) was quite similar in the 3 regimens, the overall objective response rate (C: 8573/93; E: 75/66/85; M: 58/59/80%) and more importantly pCR (7/16/26%) increased with regimens 2 and 3, with a rise in toxicity with TNCF ( ASCO 1995, abst. 218). If cases where remains only ″ in situ ″ are added, pCR reached 21% with NEM and 28% with TNCF. These navelbine–anthracyclins associations and dose intensity improved pCR, but the impact on survival has to be confirmed.

Fifty cases of abnormal uterine bleeding occured among women receiving tamoxifen for breast cancer have been investigated by hysteroscopy and dilatation-curetage. The histopathologic findings were the following: atrophic mucosa (11 cases), hyperplasic mucosa or endometrial polyps (34 cases), endometrial adenocarcinoma (5 cases). These results highlight the potential estrogen-like property so-called paradoxical effect of tamoxifen and its suggested oncogenic risk toward the endometrium.

Three hundred and eighty nine preoperative localizations were performed in the senology department of the Centre Jean Perrin in 349 patients presenting with an isolated radiological image with no associated clinical signs (discovered on routine or selective screening examinations). The most frequent anomaly detected was the presence of areas of microcalcifications, sometimes associated with a high-density lesion or more rarely an opacity. Systematic enlargements allowed refinement of the surgical indications and reduced the number of tumourectomies performed for benign lesions. The histological results consisted of 41% of neoplastic and borderline lesions with a predominance of in situ or microinvasive forms without lymph node involvement. The mean age at the time of diagnosis was 40 years, i.e. ten years younger that the mean age of cancer diagnosis. The percentage of subclinical cancers discovered in this way, increased by screening and improvement in surgical techniques, has been further increased by enlargements which have improved the precision of surgical indications. Stereotactic localization allows the surgeon and pathologist to more accurately define the lesion while preserving the appearance of the breast.

This retrospective study was carried out on 80 patients who had abnormalities discovered on mammography without any associated clinical signs. In some patients bilateral abnormalities were found so that 87 biopsies were carried out and this gave the result that 45 of the lesions were shown to be benign, 18 lesions were borderline and 24 lesions (27.6%) were of carcinomata. The frequency of these lesions goes up to 32% if areas of microcalcification only are considered. These tumours diagnosed in this sort of way, whether they are canal lesions or lobular lesions, usually show favourable histological features as far as invasion, size and lymphatic involvement is concerned. Borderline lesions are a histological group with as yet no fully evaluated significance but it has seemed to us interesting to describe them.

We examined the relevance of a pre-treatment single static view 99m Tc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99m Tc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following completion of anthracycline-based chemotherapy, clinical, mammographic, sonographic and pathological responses were determined. 99m Tc-sestamibi scintimammography predicted the reduction of tumor size measured by sonography and the pathological response according to Sataloff classification (p