PLoS ONE: Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression (clear cell ovarian/high grade)

PLoS ONE: Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression

"....According to FIGO grading classification, high-grade ovarian tumor cells are usually poorly histological differentiated [20], grow faster and highly metastatic [7]. In addition, prognosis of high-grade ovarian tumor is poor thereafter it often associates with poor survival rate [21], [22].The clear cell subtype ovarian cancer accounts for approximately 6% of all epithelial ovarian tumors and most cases of this subtype are high-grade tumor exhibiting an aggressive phenotype [3], [22], [23]. Our study showed that both mRNA and protein levels of PITX2 was frequently upregulated in ovarian cancer particularly in the high-grade and clear cell subtypes, indicating that PITX2may play an important role in driving aggressive phenotypes in ovarian cancer.....

see blogger's note: Medical News: More Good Data for PARP Blocker (Olaparib) in Ovarian Ca - in Meeting Coverage, ASCO from MedPage Today

Blogger's Note: see blog postings 'olaparib' (searchable) of March 27th and March 8th and others; also use NEJM search for more information on ovarian cancer/Olaparib

Medical News: More Good Data for PARP Blocker in Ovarian Ca - in Meeting Coverage, ASCO from MedPage Today

not yet recruiting: Cyclophosphamide and Vaccine Therapy in Treating Patients With Stage II-III Breast, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

Cyclophosphamide and Vaccine Therapy in Treating Patients With Stage II-III Breast, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

This study is not yet open for participant recruitment.

Verified May 2012 by Mayo Clinic

First Received on May 23, 2012.   Last Updated on May 24, 2012   History of Changes

Sponsor:	Mayo Clinic
Information provided by (Responsible Party):	Keith Knutson, Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier:	NCT01606241

Massachusetts Moves to Require End-of-Life Talks

Mass. Moves to Require End-of-Life Talks:
WBUR radio and Kaiser Health News report that the Massachusetts Senate has quietly approved a measure requiring doctors and nurses to discuss end of life options with patients who have a terminal illness. The Palliative Care Awareness bill was included as part of a sweeping health reform measure and, remarkably, was not controversial. It was supported by both Republicans and Democrats and by a wide range of advocacy groups, including leading right-to-life organizations.

pdf: Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

pdf:  Family perspectives in lynch syndrome becoming afamily at risk, patterns of communication andinfluence on relations 

Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 Abstract:
Background: A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer.

Methods: Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles.

Results: Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e.g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling.

Conclusions: Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.

What's Hot at ASCO This Year? (Brentuximab/ovarian cancer/CD30)

What's Hot at ASCO This Year?

".... Another study that builds on a previous breakthrough screened more than 1000 patients with nonlymphoma malignancies for high CD30 expression (Abstract 3069). A drug targeting this molecular defect, brentuximab (Adcetris, Seattle Genetics), has recently been approved for Hodgkin's lymphoma, but the new study found the CD30 defect in patients with mesothelioma and in those with testicular and ovarian cancer. The next step will be to see if these patients respond to the drug, Dr. Vogelzang explained.....

Physician Group Says No to Kittens in Medical Training

Physician Group Says No to Kittens in Medical Training

 The group, the Physicians Committee for Responsible Medicine (PCRM), asked a branch of the US Department of Agriculture (USDA) yesterday to investigate the use of kittens in the center's pediatric residency program. The PCRM said that the medical center is violating the Animal Welfare Act, which governs healthcare facilities that use live animals for research, testing, or training.

Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer? PLD (pegylated liposomal doxorubicin)

Squamous Cell Carcinoma of the Oral Cavity in Non smokingWomen: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Abstract
Purpose.
To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.

Patients and Methods.
In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.

Results.
All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m(2) given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD.

Conclusion. 
Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer. 

The finding of oral SCC in patients on long-term PLD
maintenance should alert oncologists to have a high index of
suspicion with any oral complaints that arise, and suggests a
possible need for regular oral examinations in this treatment
population. How long to continue maintenance with PLD after
a CR has been achieved is an unanswered question. The possible
risks to patients receiving maintenance PLD beyond CR
must be weighed against the presumed benefits of delaying
ovarian cancer recurrence on an individual basis.

paywalled: Early Postoperative CT as a Prognostic Biomarker in Patients With Advanced Ovarian, Tubal, and Primary Peritoneal Cancer Deemed Optimally Debulked at Primary Cytoreductive Surgery

Early Postoperative CT as a Prognostic Biomarker in Patients With Advanced Ovarian, Tubal, and Primary Peritoneal Cancer Deemed Optimally Debulked at Primary Cytoreductive Surgery

CONCLUSION:

Our study showed that residual disease larger than 1 cm was present on early postoperative CT in almost half of the patients deemed to have optimally debulked disease at primary cytoreduction.

[Biomarker for colorectal cancer] - Lynch Syndrome/MSI/KRAS/BRAF

[Biomarker for colorectal cancer]

Abstract
Discovery of usable molecular biomarkers is the step closer to a realization of personalized therapy for patients with colorectal cancer(CRC). Herein we present an update of the most recent data on promising biological prognostic and/or predictive markers, including microsatellite instability(MSI) and KRAS/BRAF mutations. Additionally, we propose a new genetic classification for CRC based on MSI and KRAS/BRAF mutation status (a 2 x 3 matrix). The 2 x 3 matrix is constructed of 6 cells that are made by [MSI/non-MSI] x [BRAF mutant/KRAS mutant/wild type of the both genes].

All of CRC including Lynch syndrome could be classified without overlapping into the 6 cells. More interestingly, each cell has each promising biological prognostic and/or predictive feature, which will help clinicians to make personalized treatment strategy for each CRC patient.

paywalled: Management and Prognosis of Clear Cell Borderline Ovarian Tumor.

Management and Prognosis of Clear Cell Borderline Ovarian Tumor.:

Abstract
BACKGROUND: The clear cell borderline ovarian tumor (CCBOT) of the ovary is a rare tumor accounting for less than 1% of BOT. Fewer than 25 cases have been reported in the literature (including details on clinical management and outcomes). The aim of this study was to determine the prognosis of a series of CCBOTs collected in 2 reference centers.
PATIENTS AND METHODS: This was a retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion.
RESULTS: Twelve patients were identified between 2000 and 2010. The median age of patients was 68 years (range, 36-83 years). Two had been treated conservatively and 9 radically (data unknown in 1). The tumor was unilateral in 11 cases. All patients had stage I disease. All cases were CCBOT with an adenofibromatous pattern. Stromal microinvasion or intraepithelial carcinoma was histologically associated in 2 and 3 cases, respectively. Four of the 12 patients had synchronous endometrial disorders (but no endometrioid carcinoma). No cases were histologically associated with endometriosis. Four patients were lost to follow-up. Among 8 other patients, after a median period of 28 months (range, 2-129 months), no recurrence had occurred (1 patient had died of another disease).
CONCLUSION: Clear cell borderline ovarian tumor carries a good prognosis. All tumors are (blogger's note - 'were' in this study of 12 pts) stage I; therefore, surgical staging is not necessary in most of the cases. Conservative treatment could be proposed to young patients, but uterine curettage would then be required in cases of uterine preservation.

paywalled: Comparability of stage data in cancer registries in six countries: lessons from the international cancer benchmarking partnership - Walters - International Journal of Cancer - Wiley Online Library

 
Comparability of stage data in cancer registries in six countries: lessons from the international cancer benchmarking partnership 

Abstract

The International Cancer Benchmarking Partnership is investigating cancer survival differences between six high-income nations using population-based cancer registry data. Differences in overall survival are often explained by differences in the stage at diagnosis and stage-specific survival. Comparing stage at diagnosis using cancer registry data is challenging because of different regional practices in defining stage, despite the existence of international staging classifications such as TNM. This paper describes how stage data may be reconciled for international analysis. Population-based cancer registry data were collected for 2.4 million adults diagnosed with colorectal, lung, breast (women) or ovarian cancer during 1995-2007 in Australia, Canada, Denmark, Norway, Sweden and the United Kingdom. The stage data received were coded to a variety of international systems, including the TNM classification, Dukes' for colorectal cancer, FIGO for ovarian cancer, and to national 'localised, regional, distant” categorisations. To optimise comparability for analysis, a rigorous and repeatable process was defined to produce a final stage variable for each patient. An algorithm was also defined to map TNM, Dukes' and FIGO to a “localised, regional, distant” categorisation. We recommend how stage data should be recorded and processed to optimise comparability in population-based international comparisons of stage-specific cancer outcomes. The process we describe to produce comparable stage data forms a benchmark for future research. The algorithm to convert between TNM and a “localised, regional, distant” categorisation should be valuable for international studies, until global consensus is achieved to adhere to a single staging system like TNM.

Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

UNC Kidney Center:  thrombotic microangiopathy
                           ~~~~~~~~~~~~~~~~~~

Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

"Treatments for recurrent ovarian cancer result in clinical
benefit and prolongation of survival times. However, our findings suggest that platinums, PLD (in large cumulative doses), bevacizumab, and possibly gemcitabine may result in cumulative kidney damage. Awareness of these long-term complications should open the way for studies on treatment strategies designed to minimize renal complications."

Abstract

Abstract Background and Objective

Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions.

(Kidney damage was defined by pathologic abnormalities
or markers of damage, including abnormalities on blood
and urine tests and radiologic studies.)

Patients and Methods. 

Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997–2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002–2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m² for >3 months and were staged according to the National Kidney Foundation guidelines.

Results. 

Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy. 

Conclusions. 

CKD (chronic kidney disease) is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

• Chronic kidney disease
• Ovarian cancer
• Pegylated liposomal doxorubicin
• Renal thrombotic microangiopathy

PLoS ONE: The KRAS-Variant Is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer (study of pts with both ovarian and breast cancers)

Blogger's Note: the other cancers (KRAS mutations) referred to beyond ovarian and breast cancers include references to lung and melanoma cancers; KRAS mutations have been established in colorectal cancers, however, there are no references on this particular subject within this research article regarding Lynch Syndrome -
an ongoing area of specific research (re: KRAS/Lynch Syndrome/blog posting of May 16, 2012 Jnl ASCP)
                                      ~~~~~~~~~~~~~~~~~~~
PLoS ONE: The KRAS-Variant Is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer


Table 1. The KRAS-variant is significantly associated with uninformative breast and ovarian cancer patients.
doi:10.1371/journal.pone.0037891.t001

Purpose

A germline microRNA binding site-disrupting variant, the KRAS-variant (rs61764370), is associated with an increased risk of developing several cancers. Because this variant is most strongly associated with ovarian cancer risk in patients from hereditary breast and ovarian families (HBOC), and with the risk of premenopausal triple negative breast cancer, we evaluated the association of the KRAS-variant with women with personal histories of both breast and ovarian cancer, referred to as double primary patients.

Conclusions

These findings further validate the importance of the KRAS-variant in breast and ovarian cancer risk, and support the association of this variant as a genetic marker for HBOC families previously considered uninformative.

Introduction 

Hereditary breast and ovarian cancer (HBOC) syndrome is an inherited cancer-susceptibility syndrome marked by an increased risk of developing both ovarian cancer and breast cancer [1]. Families generally considered as having HBOC syndrome are those with multiple family members that have one of these cancers, especially at young ages, or an individual with a cancer in both organs, a “double primary” patient. While this is a relatively rare presentation, a substantial number of women develop both breast and ovarian primaries over their lifetime. While BRCA1 and BRCA2 are strongly associated with HBOC syndrome [2], a large number of HBOC families and women with double primary cancer do not have detectable genetic mutations (herein referred to as “uninformative” patients).
The chances of identifying a mutation causative for HBOC increase when testing individuals diagnosed with double breast/ovarian primaries [3]–[5]. However, a recent report suggests that the rates of BRCA mutations are not higher in a patient with a double primary without a family history than that for isolated first degree relative pairs with single primaries (14% versus 17% with mutations, respectively) [4]. This supports the importance of family history even in patients with double primary cancers. Although BRCA mutations were found in 49% of double primary patients in this recent analysis, it should be noted that this indicates that over half of double primary patients do not have a known genetic cause for their disease. This is consistent with other reports of these patients [3], [5].............The goal of this study was to determine the association of the KRAS-variant with women with double primary breast and ovarian cancer, to further validate the association of this variant with HBOC families. Findings here support the importance of the KRAS-variant in uninformative HBOC families as well as in predicting the risk of multiple primary cancers in women.......

Association of the KRAS-variant with Multiple Cancers in All Patients

Because the KRAS-variant has been found to be associated with an increased risk for other cancers besides breast and ovarian cancer [11], [15] we tested the hypothesis that the KRAS-variant would predict for an increased risk of developing additional cancers in this double primary cohort, regardless of BRCA mutation status. For 183 of the patients in our study where this information was available, 79.2% (n = 145) had reported just the two cancers (breast and ovarian), 12.0% (n = 22) had two separate primary breast cancers and also ovarian cancer, and 8.7% (n = 16) had cancer in an additional organ outside of the breast and ovary (triple primary).