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Biomedical subjects

J M Nogaret

Publications and source records attributed to J M Nogaret.

At least 19 recordsLinked to original sources

Sentinel lymph node imaging and research after bone scintigraphy in breast cancer patients.

The aim of the study is to see if Bone Scan (BS) - when performed the day before the operation-interferes with the results of the Sentinel Lymph Node (SLN) technique using radiocolloids (their pre-operative imaging and their peroperative research). Therefore, the data of 393 patients who had one selective lymphadenectomy of the SLN(s) followed by the complete axillary node (AxN) clearance for Breast Cancer and among whom 309 patients had one BS the day before the operation (and just before the injection-s for the SLN) and 84 did not, were analysed and compared. The two series presented the same characteristics with regard to: age, clinical staging of the tumour, kind of injection-s performed (intradermic and paratumoural and/or intraparenchymal and peritumoral), pathological size of the tumour, percentage of cases with no AxN invasion, total number of AxN removed by the surgeons. The percentages of no axillary SLN visualisation, the mean numbers of axillary SLN visualised on pre-operative lymphoscintigram as well as of SLN removed by the surgeons were not statistically different in the groups of patients with (respectively, 12.11, 2.6 and 3.03) and without BS (respectively, 12.99, 2.7 and 2.96). More noteworthy, the false negative (FN) rate of the SLN technique, albeit having a higher observed value in the group with BS (9.6%, 12/125), did not differ significantly from that in the group without BS (5.6%, 2/36). The accuracies (overall correct classification rates), the sensitivities and the negative predictive values of the SLN technique also did not differ significantly between the two groups. It is concluded that the SLN technique can be accurately performed just after one BS.

Adult↗

Immediate breast reconstruction with implants and adjuvant chemotherapy: a good option?

Immediate breast reconstruction using implants is a currently practiced intervention. However, it is exposed to the potential adverse effects of adjuvant therapies necessitated for cancer control. Patients with implants, receiving adjuvant chemotherapy, were compared with those not necessitating chemotherapy to evaluate the real impact of this combination of treatment modalities on the final outcome. Cosmetic results were not influenced by the adjunction of chemotherapy, but a higher rate of implant infection was observed in the chemotherapy group (10.7% versus 1.5% p = 0.0084). This observation needs to be kept in mind when selecting patients for immediate breast reconstruction with implants.

Adenocarcinoma↗

How 'hot' is the pathologically positive sentinel lymph node in breast cancer patients?

When many lymph nodes are found by using lymphoscintigraphic techniques performed to detect the sentinel lymph nodes (SLNs) in breast cancer, it is usual to find that the 'hottest' SLN is not always the node that is pathologically positive (pN+). Various criteria have been proposed to define which radioactive lymph nodes should be removed. In order to determine the frequency with which the hottest SLN 'fails' to be pN+, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analysed our cases in which more than one SLN was detected and where there was also at least one pN+ node. From a series of 181 patients, 40 were selected. In 11 of these 40 cases (27.5%), the hottest SLN was not pN+. Radioactivity levels in the pN+SLN of these 11 patients ranged from 2% to 94% of the activity of the hottest SLN. Twenty-one patients (52.5%) showed only micrometastatic (pN1a) disease in one or more SLNs. In four of these patients (19%) the pN1a SLN was not the hottest node. Two of the patients had radioactivity levels in the pN+SLN which were more than 50% of that of the hottest SLN. In another two of these patients (9.5%), radioactivity levels were lower than 50% of that of the hottest node (respectively, 38% and 2%). However, in these two last cases, the first and hottest SLN removed surgically was found, by the pathologist, to consist of six nodes. Macrometastases (dimensions greater than 2 mm) were found in 19 patients. In 12 of these patients, the hottest SLN was macrometastatic although macrometastases and/or micrometastases were found in other 'cooler' SLNs in four of them. In another seven of these patients (36.8%), macrometastases were found in SLNs with radioactive levels lower than 51% of that of the hottest node. One patient (with three SLNs) out of the 40 (2.5%) had one SLN pN+ with less than 10% of that of the hottest. In fact, it contained only one micrometastasis and its activity was equal to 2%. Upon pathological examination, however, the hottest lymph 'node' was found to consist of six nodes. It is concluded that, with four intra-mammary and peritumoural injections of 99mTc labelled nanosized colloids of Human Serum Albumin (Nanocoll R: Sorin: 74 MBq and 0.05 mg per injection) performed 18-24 h before using a gamma probe to detect the SLNs, the hottest SLN was not the pathologically positive node in 27.5% of patients in our series. By using the activity in the hottest SLN as the reference point, and 10% of this activity as the lower threshold for removing active SLNs, the sensitivity of the technique is 97.5%.

Adult↗

Endometrial disorders in 406 breast cancer patients on tamoxifen: the case for less intensive monitoring.

OBJECTIVES: To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN: Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS: Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION: Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.

Adenocarcinoma↗

Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.

PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.

Adult↗

[Sentinel node involvement in T0-T1 breast cancers].

STUDY AIM: Determination of axillary lymph node status is crucial in diagnosis of early breast cancer. However thanks to an early diagnosis, an increasing number of axillary lymph node dissections are free of disease. This raises questions about the need for this procedure. The study aim was to report an experience with lymphadenectomy and sentinel node mapping in patients with T0-T1 carcinoma of the breast. METHODS: Between November 1997 and December 1999, 84 consecutive women (T0-T1 N0 according to the 1987 UICC classification) with recently diagnosed breast cancer, were included in this study for identification of the sentinel lymph node (SLN). The SLN was removed and submitted for histological examination. All patients underwent axillary dissection; nodes from levels I and II (Berg's classification) were excised and submitted to histological examination. RESULTS: The average tumor diameter was 12.7 mm (range, 3 to 25 mm). The lymphatic mapping technique was obtained after injection of the isotope into the breast around the tumor in 53/84 patients: the sentinel lymph node was the only positive node in 10 patients and it was positive in 5 patients with other axillary nodes. In 15/84 patients, an intradermal injection of blue dye was used; two sentinel nodes were positive and one falsely negative. In 16/84 patients, an interdermal injection of blue dye was used to make up for. In this study, the sentinel node was positive in three patients and falsely negative in one patient. The discrepancy was due to an important involvement of an axillary area excluded from the lymphatic channels. 22/84 patients (26%) had a metastatic spread to the axillary nodes. 30/84 patients had also an isotopic captation in another lymph node group (internal mammary). CONCLUSION: This study confirms that lymphatic mapping is technically possible in the patients with T0-T1 breast cancer and that the histological characteristics of the sentinel node probably reflect the histological characteristics of the rest of the axillary lymph nodes, but do not provide any information about the other lymph node sites.

Adult↗

[Breast cancer and pregnancy. Review of the literature].

INTRODUCTION: The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis. MATERIALS AND METHODS: This review examines the diagnosis, prognosis, and management of cancer during pregnancy; both in terms of the cancer's effect on the pregnancy, and the pregnancy's effect on the cancer. RESULTS: Diagnostic procedures (breast sonography) and excisional biopsies are necessary to reduce the delay of several months or more after discovery of a mass and before treatment. No histological difference, between patients with pregnancy-associated breast cancer and patients with non-pregnancy-associated breast cancer, was diagnosed. CONCLUSION: The treatment is linked to the effects of adjuvant therapy on the fetus.

Adult↗

Comparison of immunohistochemical and biochemical measurement of steroid receptors in breast cancer: are both still necessary?

In our institute, the oestrogen and progesterone receptors of breast cancer samples are analyzed by biochemistry and immunohistochemistry. The purpose of this study is to evaluate and compare both techniques and establish whether one of them should be used in preference to the other. The probability of getting a positive or negative result with each technique was the same regardless of the method used as reference. The biochemical method uses a larger volume of tissue to determine the receptor status than immunohistochemistry. In some cases, this means a loss of valuable information. If we only use one technique, there is the potential to misclassify +/- 11% of patients. According to these results and in the knowledge that the major interest of steroid receptors' status remains in the domain of therapeutic decisions, we advise using immunohistochemistry first and biochemistry if there is a negative result. This would spare tumour tissue for new research studies.

Journal Article↗

Immediate breast reconstruction with saline-filled implants: no interference with the oncologic outcome?

The possible adverse effects on cancer control due to immediate breast reconstruction have been addressed recently for both silicone-filled implants and flap reconstruction. To evaluate those possible effects after immediate breast reconstruction with saline-filled implants, 49 patients reconstructed with saline-filled breast implants at the Jules Bordet Cancer Institute were studied. Selection was only based on the possibility to find a matched patient. These patients were matched with a control group of 49 matched women with breast cancer treated in the same center by mastectomy without any type of breast reconstruction. The two groups were comparable according to age at diagnosis (within 3 years), year of diagnosis (same year), stage of the tumor, histology, and nodal status. The only difference between the two groups was that radiation therapy was applied to some of the patients who were not reconstructed (due to tumor location). The results show, in terms of local recurrences, distant metastasis, and deaths, no significant difference between the two groups, even for the irradiated patients, within a mean follow-up period of 72 months (range, 24 to 108) months.

Adult↗

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.

PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.

Aged↗

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer.

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

Adult↗

Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. Correlation with oncogene amplification in 160 cases.

Overexpression and amplification of the HER-2 oncogene in patients with breast cancer has correlated with early onset of metastasis, resistance to hormonal therapy and some forms of chemotherapy, and shortened survival. Therefore, evaluation of this putative prognostic or predictive factor seems critical. Because different antibodies are used for the detection of the 185-kd HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibodies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpression was found in 17.2% and 12.5% of cases using antibodies against the external (TAB250) and internal (CB11) domains of the protein, respectively, and in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in situ hybridization was successful in all 160 tumors, and amplification was found in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misclassification rate, 9.6% (sensitivity, 67%; specificity, 97.5%).

Antibodies↗

[Why radiation for the postmastectomy patient?].

We can identify a subgroup of patients with a high risk of loco-regional relapse after mastectomy. When those patients are irradiated, their absolute loco-regional relapse risk drops for more than 10% with a relative risk reduction of 66% (p < 0.0001). The severe complication rate is below 1%. With earlier radiotherapy techniques, there was an excess in long term cardiac mortality among irradiated patients. Even if the breast specific survival was improved with radiotherapy, the overall survival was not better. Three recent randomised trials have shown that postmastectomy radiotherapy adds 10% survival benefit to an adjuvant systemic treatment. The impact of radiotherapy on overall survival is more pronounced for less advanced tumors.

Breast Neoplasms↗

Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen.

Retinoids constitute a very promising class of agents for the chemoprevention or treatment of breast cancer. These retinoids exert their biological activity through two distinct classes of retinoic acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma) and their numerous isoforms which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. With respect to these numerous receptor sub-types, the retinoid-induced effects at the biological level include marked modifications with respect to both cell proliferation and cell death (apoptosis), and also in the induction of differentiation processes. The present study aims to characterize the effect which four retinoids (TTNPB, 9-cis-RA, LGD 1069, 4-HPR) with distinct RAR/RXR binding properties induced on various in vitro and in vivo mouse and human breast cancer models. The experiments with the retinoids were carried out in comparison with the anti-estrogen tamoxifen and the anti-progestagen RU-486 compounds. The results show that the 6 compounds under study were markedly more efficient in terms of growth inhibition in the human T-47D cell line when maintained under anchorage-independent culture conditions than when maintained under anchorage-dependent ones. While RU-486 exhibited a weak statistically significant (p < 0.05) influence on the growth of the T-47D stem cells, tamoxifen had a marked inhibitory influence on the growth of these cells. Of the four retinoids, 4-HPR was the least effective since the lowest doses tested (1 and 0.1 nM) exhibited no statistically (p > 0.05) significant influence on the growth of the stem cells. The most efficient retinoid was TTNPB. It was only at the highest dose (10 microM) that tamoxifen and RU-486 showed a weak inhibitory influence on the growth of the T-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-HPR being the most efficient (P < 0.001) at the highest dose, but ineffective (P > 0.05) at the lowest. Tamoxifen and TTNPB were tested in vivo on hormone-sensitive (HS) and hormone-insensitive (HI) strains of the MXT murine mammary carcinoma. While TTNPB appeared to be equally efficient in terms of growth inhibition in both MXT-HS and MXT-HI models, tamoxifen had only a marginal inhibitory influence on the growth of the MXT-HI strain but did inhibit growth in the case of the MXT-HS one. TTNPB was markedly more efficient than tamoxifen in terms of both inhibiting the cell proliferation level (measured by means of computer-assisted microscopy applied to Feulgen-stained nuclei, a method which enables the percentage of cells in the S phase of the cell cycle to be determined) and triggering cell death (measured by means of the determination of the transglutaminase activity) in both the MXT-HI and MXT-HS models. The very significant TTNPB-induced inhibition of the macroscopic MXT-HS growth rate relates to the triggering of cell death (apoptosis) rather than to an inhibition of cell proliferation. All these results clearly indicate that retinoids are very efficient agents against breast cancer, at least as efficient as tamoxifen.

Alitretinoin↗