Pyoderma gangrenosum and breast cancer: a case report

The authors report a case of pyoderma gangrenosum (PG) following a breast lumpectomy for a relapse of a breast cancer. The treatment has associated a systemic corticosteroid therapy and local wound care with vacuum assisted closure Vacuum-Assisted Closure and skin graft.     

Breast adenocarcinoma discovered by orbital metastases: a case report and review of the literature

Ocular metastasis of breast cancer has become more frequent since therapy increases patients' survival. It is therefore important to recall this diagnosis. We report the case of a 73-year-old patient who had orbital metastases of an unknown breast cancer. The commonest clinical sign at diagnosis is exophthalmia. Prognosis is usually pejorative once diagnosis is performed. Standard treatment is radiotherapy and requires a multidisciplinary approach.     

Pregnancy after breast cancer: an update

Breast cancers account for one third of cancer patients of childbearing age. Given the trend for women to delay childbearing, many of them will not fulfill their parental project at diagnosis of a potential breast cancer. Thus, planning pregnancies in young patients with a history of breast cancer is increasingly becoming a common situation. In this difficult context, several issues have to be discussed with the patient, such as post-chemotherapy premature ovarian failure, fertility-sparing techniques, risk of cancer recurrence or optimal time between cancer and future pregnancy. Potential obstetrical complications, long-term teratogenicity of anti-cancer drugs or breast-feeding are another points that have to be discussed with the patient and her husband. The aim of this updated review of literature was to provide answers to the numerous questions that may be encountered in this type of highly difficult situation. Thus, planning a pregnancy in breast cancer patients seems to be possible with, in one hand, a multidisciplinary approach in order to answer different questions and to avoid side effects of chemotherapy. In the other hand, a close and specialized obstetrical monitoring should be proposed in order to anticipate potential obstetrical complications.     

Role for aromatase inhibitors as adjuvant treatment of breast cancer in menopaused women: facts and questions in 2005

After a dominant role for more than 30 years, tamoxifen has been progressively replaced by aromatase inhibitors as adjuvant treatment for breast cancer in the menopaused woman. We present here a recall of the mechanisms of action involved together with a review of clinical trials leading to the current situation. Giving trial results in detail, we discuss the current evidence as well as open questions. The populations concerned and trial methodologies are analyzed. Comparative tolerance is detailed. Several questions remain open, either due to the lack of evidence to be obtained from ongoing trials or sufficient follow-up. The evidence presented is commented in light of the American (ASCO) and European (Saint-Gallen) or French (Saint-Paul) guidelines.     

Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study

Abstract.   Gaarenstroom KN, van der Hiel B, Tollenaar RAEM, Vink GR, Jansen FW, van Asperen CJ, Kenter GG. Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study. Int J Gynecol Cancer 2006; 16(Suppl. 1): 54–59.
The outcome of screening and prophylactic surgery in 269 women at high risk of hereditary ovarian cancer is reported. Screening was performed using transvaginal ultrasound and serum CA125 testing. Mean follow-up was 26 months (583 person-years). A total of 113 (42%) of 269 women had a pathogenic BRCA1 or BRCA2 mutation, and 127 (47%) of 269 women underwent salpingo-oophorectomy. No occult cancers were found. In eight women having both elevated CA125 levels and abnormal ultrasound findings, a malignancy was found. Four of these cancers (one borderline, one stage Ia, one stage IIIb, and one stage IIIc ovarian or peritoneal cancer) were detected at the first screening visit. One stage IIIb and one stage IIIc cancer were detected at the second screening visit after 12 months, and two interval stage IIIc and IV cancers were detected 8 and 10 months after the first screening visit. No peritoneal carcinoma was found among those 114 women who underwent bilateral salpingo-oophorectomy with normal or benign pathology results, after a mean follow-up of 16 months (152 person-years). We conclude that the efficacy of screening women at high risk of ovarian cancer seems poor because the majority of cancers were detected at an advanced stage.     

Histology of Prophylactically Removed Ovaries from BRCA1 and BRCA2 Mutation Carriers Compared with Noncarriers in Hereditary Breast Ovarian Cancer Syndrome Kindreds

Objective. The literature reports conflicting studies claiming premalignant histological features in benign ovaries from women who may have hereditary predilections for ovarian carcinoma. To test the veracity of these claims, this investigation studied ovaries prophylactically removed from members of hereditary breast ovarian cancer (HBOC) syndrome families who carry BRCA1 and BRCA2 mutations and compared these with the ovaries of mutation-negative women from the same HBOC syndrome kindred.Methods. Sixty cases of women from HBOC syndrome families who had undergone prophylactic oophorectomies and whose BRCA1 and BRCA2 mutation status had been tested were selected from our database. Thirty had tested positive for BRCA1 mutations, 3 carried BRCA2 mutations, and 27 were negative for both BRCA1 and BRCA2 germline mutations. Histologic material from each case was examined by light microscopy blinded to the mutation status. Histologic features, previously reported to be possible precursor lesions for ovarian cancer, were quantified. Data from BRCA1 and BRCA2 mutation carriers were compared with those from mutation-negative cases in the direct line of genetic inheritance from the same HBOC syndrome families.Results. Statistical analysis found that a more frequent occurrence of ovarian surface micropapillae in 87% of mutation carriers compared with just 55% of mutation-negative cases was the only histologic feature which was significantly different between the two groups (P = 0.39). Cortical clefts tended to be deeper in the ovaries of mutation carriers, but this did not reach significance (P = 0.051). There were no other significant histologic differences between the ovaries removed from mutation carriers and those from noncarriers.Conclusions. The results of our large and prospectively controlled, blinded study contrast with those reported from smaller, unblinded investigations. Except for the possible biological significance of surface micropapillae on ovaries from BRCA1 and BRCA2 mutation carriers, we found no histologic evidence for a genetically determined ovarian carcinoma precursor lesion.     

BRCA1 and BRCA2 mutations in ovarian cancer: Covariation with specific cytogenetic features

Abstract. Koul A, Malander S, Loman N, Pejovic T, Heim S, Willen R, Johannsson O, Olsson H, Ridderheim M, Borg Å. BRCA1 and BRCA2 mutations in ovarian cancer: covariation with specific cytogenetic features.
We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.     

Demographic and genetic characteristics of patients with borderline ovarian tumors as compared to early stage invasive ovarian cancer

OBJECTIVE: Evaluation whether Jewish founder mutations in BRCA predispose to borderline tumors as they do to early invasive ovarian cancers. METHODS: All Jewish women with borderline or invasive ovarian tumors, diagnosed over a 5-year period (1994-1999), were identified in the frame of a nationwide epidemiological study on ovarian cancer in Israel. Out of a total of 1489 patients, 1269 were interviewed; of them 256 (20.2%) patients were identified with stage I and II invasive epithelial ovarian tumors, and 233 (18.3%) patients were identified with borderline tumors. All patients underwent interviews, and blood or tissue samples from 117 borderline tumors and 161 early stage invasive tumors were analyzed for the presence of the 185delAG and 5382insC BRCA1, and the 6174delT BRCA2 Jewish founder mutations. RESULTS: Patients with borderline tumors were younger at diagnosis, and more frequently of the serous type (P < 0.001) as compared to patients with early stage ovarian cancer. Prevalence of Jewish founder mutations in BRCA1 and BRCA2 was only 4.3% of patients with borderline tumors as compared to 24.2% of patients with early stage ovarian cancer (P = 0.001). CONCLUSIONS: This nationwide study comparing patients with early stage borderline and invasive epithelial tumors of the ovary confirms our previous pilot study that showed a lower incidence of BRCA mutations in patients with borderline tumors. Our results suggest that the genetic predisposition and the molecular mechanisms underlying tumor initiation differ between invasive and borderline tumors of the ovary.     

BRCA1 and BRCA2 mutations among ovarian cancer patients from Colombia

Objective

The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Colombia has not yet been explored. Five founder mutations have been identified in two previous studies of breast cancer patients in the Bogota region [1,2]. It is important that the frequency of mutations be established among unselected cases of ovarian cancer in order to estimate the genetic burden of this cancer in Colombia and to plan genetic and preventive services.

Methods

We enrolled 100 unselected women with ovarian cancer from the Bogota region, and from northern and southern central regions of Colombia. A detailed family history was obtained from each patient and a blood sample was processed for DNA analysis. DNA quality was adequate for BRCA testing for 96 women. Mutations in BRCA1 and BRCA2 were sought using a Hispanic BRCA mutation testing panel. All mutations were confirmed by direct sequencing.

Results

Fifteen mutations were identified (two in BRCA2 and thirteen in BRCA1) representing 15.6% of the total (95% CI: 7.8% to 21.3%). Among the 15 mutation-positive families there were nine breast-ovarian cancer families, one gastric cancer family, one prostate cancer family, three uterine cancer families, and one family with no history of cancer. A single founder mutation in BRCA1 (3450del4) was seen in 11 patients.

Conclusion

In summary, BRCA1 founder mutations are common in Colombian women with ovarian cancer. Approximately 11.5% of all ovarian cancer cases in the Bogota region are attributable to a single BRCA1 founder mutation.     

There is no decision to make: experiences and attitudes toward treatment-focused genetic testing among women diagnosed with ovarian cancer

Objective

There is growing evidence that the BRCA mutation status of women newly diagnosed with ovarian cancer may be used to make treatment recommendations in the future. This qualitative study aimed to assess women's attitudes and experiences toward treatment-focused genetic testing (TFGT).

Methods

Women (N = 22) with ovarian cancer who had either (i) advanced disease and had previously had TFGT (n = 12) or (ii) had a recent ovarian cancer diagnosis and were asked about their hypothetical views of TFGT (n = 10), were interviewed in-depth.

Results

This study demonstrates that patients diagnosed with ovarian cancer found the concept of TFGT acceptable with the primary motivation for genetic testing being to increase their treatment options. Women reported that there was no decision to make about TFGT, and the advantages of TFGT were perceived to outweigh the disadvantages. Many women described elements of resilience and active coping, in the context of hypothetical and actual TFGT.

Conclusions

Resilience and active coping strategies are important factors that warrant investigation as potential moderators of psychological distress in future prospective studies exploring the optimal way of offering BRCA genetic testing to women newly diagnosed with ovarian cancer, and to assess the impact of TFGT upon patients' survival, psychological distress, and quality of life.     

Cultures of ovarian surface epithelium from women with and without a hereditary predisposition to develop female adnexal carcinoma

AIM: Conflicting evidence exists on whether in vivo morphological characteristics can distinguish Ovarian Surface Epithelium (OSE) of ovaries obtained from women with and without a predisposition to develop female adnexal (ovarian and fallopian tube) carcinoma. This study aims to detect differences in growth potential and morphology that are maintained or specifically expressed in vitro. STUDY DESIGN: Ovarian surfaces were scraped to retrieve OSE cells from 56 women at hereditary high risk for female adnexal carcinoma, of whom 33 are BRCA1 and four are BRCA2 mutation carriers (Predisposed OSE, POSE) and from 26 women without such risk (Non Predisposed OSE, NPOSE). Number of passages and total cell yield until last passage, as well as morphology was compared between both groups. To confirm morphology, the expression of epithelial, mesothelial, and fibroblast markers was assessed. RESULTS: Both POSE and NPOSE cultures displayed similar growth potential and morphology. The expression of epithelial markers cyto-keratins 7 and 8 was similar between both groups. Only in cultures in which cells did not uniformly exhibit these markers, the percentage of cells expressing these markers was significantly lower at last passage when compared to the initial culture. In these latter cultures, cells that were morphologically indistinguishable from fibroblasts were observed. Mesothelial marker calretinin was expressed in 75% of cells of both POSE and NPOSE cultures and correlates with cyto-keratins 7 and 8 expression. CA 125 expression was equally low in POSE and NPOSE cultures (4.3%). Fibroblast markers FSM and vimentin were expressed in 100% and collagen IV was expressed in 16% of cells in all cultures. CONCLUSION: OSE cells derived from women with a hereditary predisposition to develop female adnexal cancer possess similar in vitro characteristics as OSE from women without this predisposition. On basis of our results, it seems advisable to study only 100% cyto-keratins 7 and 8 positive OSE cultures, since contamination of fibroblasts in some primary OSE cultures cannot be ruled out.