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Biomedical subjects

F Amant

Publications and source records attributed to F Amant.

At least 19 recordsLinked to original sources
PubMed2007

Body mass index and HER-2 overexpression in breast cancer patients over 50 years of age.

PURPOSE: In breast cancer, in vitro as well as in vivo experiments have shown an inverse relationship between HER-2 and steroid hormone receptors. It is unknown whether circulating estrogens affect HER-2 expression. We hypothesize that the postmenopausal body mass index (BMI) as a surrogate marker for bio-available estrogens, is inversely associated with HER-2 over-expression. PATIENTS AND METHODS: A total of 535 women over age 50 or with known postmenopausal status, with a unilateral, not previously treated, operable breast cancer were evaluated the evening prior to surgery for body weight, height, abdominal and hip circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were calculated. HER-2, estrogen receptor and progesterone receptor staining was done by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER-2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles for all parameters of body composition and tested for a trend in HER-2 expression across the 6 quantiles. Furthermore, we investigated whether BMI contributed, together with other known predictors for HER-2, in a standard multivariate logistic regression model that predicts HER-2 over-expression. RESULTS: There is a decrease in HER-2 over-expression per increasing quantile of BMI. In a multivariate model-including both steroid receptors-BMI remains an independent predictor for HER-2 over-expression. CONCLUSION: In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.

Age Factors↗
PubMed2006

New models to predict depth of infiltration in endometrial carcinoma based on transvaginal sonography.

OBJECTIVES: Preoperative knowledge of the depth of myometrial infiltration is important in patients with endometrial carcinoma. This study aimed at assessing the value of histopathological parameters obtained from an endometrial biopsy (Pipelle de Cornier; results available preoperatively) and ultrasound measurements obtained after transvaginal sonography with color Doppler imaging in the preoperative prediction of the depth of myometrial invasion, as determined by the final histopathological examination of the hysterectomy specimen (the gold standard). METHODS: We first collected ultrasound and histopathological data from 97 consecutive women with endometrial carcinoma and divided them into two groups according to surgical stage (Stages Ia and Ib vs. Stages Ic and higher). The areas (AUC) under the receiver-operating characteristics curves of the subjective assessment of depth of invasion by an experienced gynecologist and of the individual ultrasound parameters were calculated. Subsequently, we used these variables to train a logistic regression model and least squares support vector machines (LS-SVM) with linear and RBF (radial basis function) kernels. Finally, these models were validated prospectively on data from 76 new patients in order to make a preoperative prediction of the depth of invasion. RESULTS: Of all ultrasound parameters, the ratio of the endometrial and uterine volumes had the largest AUC (78%), while that of the subjective assessment was 79%. The AUCs of the blood flow indices were low (range, 51-64%). Stepwise logistic regression selected the degree of differentiation, the number of fibroids, the endometrial thickness and the volume of the tumor. Compared with the AUC of the subjective assessment (72%), prospective evaluation of the mathematical models resulted in a higher AUC for the LS-SVM model with an RBF kernel (77%), but this difference was not significant. CONCLUSIONS: Single morphological parameters do not improve the predictive power when compared with the subjective assessment of depth of myometrial invasion of endometrial cancer, and blood flow indices do not contribute to the prediction of stage. In this study an LS-SVM model with an RBF kernel gave the best prediction; while this might be more reliable than subjective assessment, confirmation by larger prospective studies is required.

Aged↗
PubMed2006

Metastatic breast cancer: sequencing hormonal therapy and positioning of fulvestrant.

Fulvestrant, a novel estrogen receptor (ER) antagonist with no agonist effects, binds, blocks, and degrades the ER, thereby downregulating cellular ER levels, which in turn leads to reduced expression of the progesterone receptor. Due to this specific working mechanism, fulvestrant is an important addition to the armamentarium of endocrine agents in advanced breast cancer (ABC). Fulvestrant has been shown to be equally effective as the third-generation aromatase inhibitor (AI) anastrozole in postmenopausal patients with hormone-sensitive ABC progressing prior to tamoxifen. In another randomized phase III trial, it was shown that fulvestrant had similar efficacy to tamoxifen in the first-line treatment of postmenopausal women with hormone receptor-positive ABC. When comparing the side effects of fulvestrant with tamoxifen and anastrozole, it was shown that fulvestrant is well tolerated compared with these agents and is associated with a lower incidence of joint disorders. Clinical benefit on fulvestrant treatment after AI therapy has been reported in a substantial number of patients (28-46%). On the other hand, it was also shown that sensitivity to further endocrine therapy is retained following progression on first-line or second-line fulvestrant (57% and 46% clinical benefit, respectively). In conclusion, fulvestrant provides us with an additional endocrine treatment option making it possible to prolong the time that patients with ABC can be treated with endocrine therapy.

Antineoplastic Agents, Hormonal↗
PubMed2006

Endometrial carcinosarcoma with osteoclast-like giant cells.

We encountered a case of endometrial cancer with a poorly differentiated epithelial component, accompanied by a compact proliferation of atypical spindle cells and osteoclast-like giant cells. Immunohistochemically, the epithelial component was EMA and prekeratin positive with vimentin-positive spindle cells, whereas the osteoclast-like giant cells were strongly immunoreactive for CD68. The description of osteoclast-like giant cells adds to the knowledge of endometrial carcinosarcoma tumor biology.

Biopsy, Needle↗
PubMed2006

The position of neoadjuvant chemotherapy within the treatment of ovarian cancer.

It is clear that primary debulking remains the standard of care within the treatment of advanced ovarian cancer (International Federation of Gynaecology and Obstetrics, FIGO, stage III and IV). Debulking surgery should be performed by a gynaecologic oncologist without any residual tumour load, or so called optimal debulking'. Over the last decades, interest in the use of neoadjuvant chemotherapy together with an interval debulking has increased. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. Neoadjuvant therapy can be used for patients that are primarily suboptimally debulked due to an extensive tumor load. In this situation, based on the randomized EORTC-GCG trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Neoadjuvant chemotherapy can also be used as an alternative to primary debulking. In retrospective analyses neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of future randomized trials to know whether neoadjuvant chemotherapy followed by interval debulking surgery is a good alternative to primary debulking surgery in stage IIIc and IV patients.

Chemotherapy, Adjuvant↗
PubMed2005

Hormone receptors do not predict the HER2/neu status in all age groups of women with an operable breast cancer.

BACKGROUND: In breast cancer, there is an inverse relationship between HER2/neu overexpression and receptors for estrogen (ER) or progesterone (PR). Some clinical observations such as the age-related association between hormone receptors and tumour grade, which predicts HER2/neu overexpression, suggest an age-related relationship. PATIENTS AND METHODS: Our study population consisted of 1362 consecutive women receiving primary surgery for non-metastatic invasive breast cancer. We compared the relationship between both hormone receptors and HER2/neu overexpression in different age groups taking other tumour characteristics into account. RESULTS: In a multivariate model, considering the overall group, a negative ER, a negative PR and a high tumour grade were predictive for HER2/neu overexpression (P <0.001). Considering 246 women aged < or =45 years, the only predictor for HER2/neu overexpression in this age category was a high tumour grade (P = 0.003). Considering the 1116 women aged >45 years, ER (P = 0.001), PR (P = 0.001) and tumour grade (P <0.001) were associated with HER2/neu (P <0.001). CONCLUSION: Our findings indicate that the association between ER, PR and HER2/neu overexpression varies with age. The hormone receptors are not an independent predictor for the HER2/neu status in young women while they are in elder patients.

Age Distribution↗
PubMed2005

Ultrasound features of different histopathological subtypes of borderline ovarian tumors.

OBJECTIVE: To describe the gray-scale sonographic and color Doppler imaging features of the most common histopathological subtypes of borderline ovarian tumors. METHODS: We analyzed retrospectively the preoperative transvaginal sonographic reports of patients with a histological diagnosis of borderline ovarian tumor. All patients were scanned consecutively by two of the investigators using transabdominal and transvaginal gray-scale imaging to assess the morphology and color Doppler to obtain indices of the blood flow. Sonographic findings were compared to histopathological data. RESULTS: A total of 113 consecutive cases were reviewed from two referral centers for gynecological oncology. At histological examination 50 tumors (44%) were classified as being serous borderline ovarian tumors (SBOT), 61 (54%) were mucinous borderline ovarian tumors (MBOT) (42 intestinal type and 19 endocervical type), and two patients (2%) presented with borderline endometrioid tumors. SBOTs and endocervical-type MBOTs had very similar sonographic features and a smaller diameter, fewer locules (usually unilocular-solid lesions) and a higher color score than intestinal-type MBOTs. Intestinal-type MBOTs were characterized by a significantly higher percentage of lesions with > 10 locules when compared with the endocervical-type MBOTs. CONCLUSION: Intestinal-type MBOTs have different sonographic features from other common borderline ovarian tumors.

Adult↗
PubMed2005

Cervical neoplasia during pregnancy: diagnosis, management and prognosis.

Pregnancy represents an exceptional opportunity for the early diagnosis of cervical cancer since visual inspection, cytological examination and bimanual palpation are considered to be part of routine antenatal care. An abnormal cervical smear should generally be managed as in the non-pregnant state. However, colposcopy and biopsies are mainly intended to exclude invasive disease because a conservative approach is preferred in cases of pre-invasive disease. The only absolute indication for conization in pregnancy is to rule out (micro-)invasive disease or make the diagnosis of invasive carcinoma when such a diagnosis will alter the timing or mode of delivery. Overall, earlier stages of cervical cancer are encountered during pregnancy compared with the general population. Although stage of disease and gestational age will largely influence the timing of the interventions, treatment of invasive cervical cancer is similar to the non-pregnant state. In strongly desired pregnancies, the use of neo-adjuvant chemotherapy in order to obtain fetal maturity should be considered and discussed with the patient. Although good evidence supports short-term safety, long-term data regarding the in-utero exposure of cytotoxic drugs need to be consolidated. After stratifying for stage, the outcome is similar to the non-pregnant state.

Biopsy↗
PubMed2005

Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer.

AIMS: To investigate the association between tumour characteristics and HER-2/neu by immunohistochemistry in primary operable breast cancer. METHODS: The association between HER-2/neu and other clinicopathological factors was evaluated in 1362 consecutive patients with primary breast cancer treated between 2000 and July 2003 in one centre. Microscopic tumour size, tumour grade, lymph node status, patient's age, oestrogen receptor (ER), progesterone receptor (PR), and joint ER/PR status were evaluated, using the chi2 test for univariate analysis and logistic regression for multivariate analysis. The hormone receptors and HER-2/neu were studied immunohistochemically. Using the HER-2/neu DAKO scoring system, scores of 0, 1+, or 2+ were defined as negative and 3+ as positive. Data for DAKO scores 2+/3+ versus 0/1+ are also presented. RESULTS: Hormone receptor negative breast cancers were more often HER-2/neu positive than hormone receptor positive cancers, both for ER (28.7% v 6.8%) and PR (19.9% v 5.9%). In multivariate analysis, both ER, PR, and tumour grade were independently associated with HER-2/neu. In ER+ tumours, HER-2/neu overexpression was significantly lower in PR+ than in PR- cases (11.5% v 5.4%). HER-2/neu overexpression (2.7%) was lowest in the large subgroup of ER+PR+ tumours with low tumour grade (grade 1-2), comprising 46.1% of all patients. CONCLUSIONS: ER, PR, and tumour grade are independent predictors for HER-2/neu overexpression in women with primary operable breast cancer. ER and PR are negatively associated with HER-2/neu, whereas tumour grade is positively associated with HER-2/neu. In women with ER+ tumours, PR status also affects the likelihood of HER-2/neu expression.

Adult↗
PubMed2002

PTEN mutations in uterine sarcomas.

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.

Exons↗
PubMed2001

Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome.

Uterine leiomyoma presenting with ascites and pleural fluid is referred to as pseudo-Meigs' syndrome. It is unclear whether common uterine leiomyomas and uterine leiomyomas causing pseudo-Meigs' syndrome are cytogenetically related or whether functionally different primary pathogenetic triggers are responsible for the differences in tumor phenotype. In this study, we investigated the possible involvement of RAD51LI and HMGA2 (formerly known as HMGIC) in initiation and/or progression of a huge uterine leiomyoma presenting as pseudo-Meigs' syndrome. The detailed cytogenetic and FISH analysis revealed the presence of two subclones with a complex karyotype, 46,XX,t(2;12)(q31;q21),ins(14;12)(q23-24;q15q21).ish del(12)(q15q15) (LL12NC01-142H1-,LL12NC01-27E12-),der(12)t(2;12)(LL12NC01-142H1+,LL12NC01-27E12-),der(14)ins(14;12)(q22;q15q15) (LL12NC01-142H1+,LL12NC01-27E12+,RAD51LI+), der(14)ins(14;12)(q23-q24;q15q21) (LL12NC01-142H1-, LL12NC01-27E12+) [20]/46,idem,del(14)(q21q24).ish(RAD51LI-) [6], indicating intragenic HMGA2 rearrangement and loss of one of the RAD51LI alleles in a derivative subclone with chromosome 14 deletion. Furthermore, RACE and RT-PCR analysis of the tumor cells did not reveal abnormal HMGA2 or RAD51LI transcripts. Additionally, the cellular subclone with intrachromosomal 14q21-q24/RAD51LI deletion showed an in vitro growth advantage over the subclone without the deletion. This observation supports a model in which accumulation of two independent mutations-a classical structural rearrangement involving HMGA2 and RAD51L1, in combination with a loss of the second RAD51L1 allele-might play a major role in the development of pseudo-Meigs' syndrome.

Adult↗