Mismatch Repair Polymorphisms as Markers of Breast Cancer Prevalence in the Breast Cancer Family Registry (NY)

open access

Materials and Methods

Study population. We selected participants enrolled in the New York site of the BCFR with available DNA (8-18). Enrollment eligibility for participants in the parent study included having to meet one of the following criteria: i) A female relative who had been diagnosed with either breast or ovarian cancer prior to the age of 45; ii) A female relative who has been diagnosed with breast and ovarian cancer at any age; iii) Two or more female relatives who had been diagnosed with breast or ovarian cancer after the age of 45; iv) A male relative diagnosed with breast cancer at any age; v) A known carrier of BRCA1 or 2 mutation. We used data collected at baseline through epidemiologic and family history questionnaires on demographics, ethnicity, history of all cancers, smoking, alcohol consumption, reproductive history, hormone use, height, weight, physical activity and dietary intake. Blood was collected at the time of recruitment, on average 5 years after diagnosis of cases (19). The current study includes 313 sister-sets (n=744) consisting of sisters discordant for breast cancer.

 In conclusion, in our family-based case-control study, we observe an increase in breast cancer risk due to alleles typically associated with Lynch syndrome cancers. These findings suggest that, while polymorphisms in MMR have, thus far, not been associated with sporadic breast cancer, deficiencies in this pathway may be relevant in familial breast cancer.

Ovarian clear cell carcinoma with plasma cell-rich inflammatory stroma: Cytological Findings of a Case

abstract

 We report a case of clear cell carcinoma (CCC) of the ovary with plasma cell-rich inflammatory stroma, a recently proposed subtype of CCC, and present the cytological findings. The patient was a 48-year-old woman, who was incidentally found to have a right ovarian tumor during the preoperative work-up for an early-stage adenocarcinoma of the uterine cervix. Cytological examination of an imprint smear of the ovarian tumor and peritoneal washing revealed solid cell clusters of irregular, often dendritic shapes, which were intermingled with many inflammatory cells. "Raspberry bodies" were not found. Histopathological examination of the extirpated ovarian tumor showed the features of CCC with plasma cell-rich inflammatory stroma. This subtype of ovarian CCC poses cytological and histological diagnostic problems, and its differentiation from dysgerminoma is often difficult, because it mostly lacks the hyaline or mucoid stroma. Irregularly shaped clusters of large polyhedral cells, coarsely clumped nuclear chromatin, and plasma cell-rich inflammatory infiltrates suggest CCC, but the cytological differences between dysgerminoma and CCC are often subtle, and immunohistochemical examinations for cytokeratin 7 or epithelial membrane antigen may be necessary. Diagn. Cytopathol, 2016.

PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions

British Journal of Cancer - open access

FROM:

PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions

G E Konecny and R S Kristeleit

BACK TO ARTICLE

Figure 1.

Role of PARP in DNA repair and main effects of PARP inhibitors. (A) Main DNA repair mechanisms, key pathway components and role of PARP1 for each pathway. (B) DNA single strand break repair by base excision repair. (C) Effect of PARP inhibition on DNA single and double strand break repair. AP, apurinic/apyrimidinic; ATM, ataxia telangiectasia; BER, base excision repair; DNA-PKcs, DNA-dependent protein kinase, catalytic subunit; DSB, double-strand break; FA, Fanconi anemia; FEN1, flap sructure-specific endonuclease 1; HR, homologous recombination; KU70 and KU80, make up the Ku heterodimer; MMEJ, microhomologymediated end joining; MRN, MRE11–RAD50–NBS1 protein complex; NBN, Nibrin; NHEJ, non-homologous end joining; PARP, poly (ADP-ribose) polymerase; PALB2, partner and localiser of BRC; PARPi, PARP inhibitor; RAD51, eukaryote gene of RAD51 protein family; SSB, single-strand break.
Full figure and legend (402K)

Table 1 - PARP inhibitors under development.

Full table

Table 2 - Most common AEs (any grade and grade 3) with olaparib treatment based on data from 2 large olaparib clinical trials. Shown are any grade AEs reported in at least 15% of patients or grade 3 AEs reported in at least 5% of patients.

Full table

Table 3 - Clinical Trials of PARP inhibitors in ovarian cancer.

Full table

Review: Plant-Based Estrogen Effects Still Not Understood

medpage
 
....At the same time, there are areas where phytoestrogens do show promise, the team emphasized. For example, in breast cancer, a 2013 analysis of 40 randomized controlled trials, 11 uncontrolled trials, and 80 observational studies led to the conclusion that soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality.

Even in this case, however, the authors indicated that there is not enough evidence to confirm the safety of using soy isoflavones in doses that are high enough (generally >100 mg/day) to obtain the anti-cancer benefits.

Conversely, some of the more widely discussed harmful effects of phytoestrogens also remain unproven. Rietjens and colleagues highlighted a 1997 study in which the soy isoflavones daidzein and genistein were found to inhibit thyroid peroxidase, but no other adverse effects on thyroid functions had been observed.

Human trials on soy isoflavones and thyroid function are entirely inconclusive, Rietjens and colleagues found.

New Articles -- EvidenceUpdates: Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis

1. abstract + comment

   Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab.

 2. NEJM - abstract
(Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743; SOLO 2 ClinicalTrials.gov number, NCT02277769.)

European Journal of Human Genetics - Table of Contents (worth reading)

European Journal of Human Genetics  (not open access)

TABLE OF CONTENTS

Volume 24, Issue 11 (November 2016)

Articles |
Short Reports |
Clinical Utility Gene Cards |
Book Review

 

eg.:

 

 Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing

 

Abstract | Full Text | PDF

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer 

Abstract | Full Text | PDF

 

The risk of re-identification versus the need to identify individuals in rare disease research ^EJHGOpen

Abstract | Full Text | PDF

Return of individual genomic research results: what do consent forms tell participants?

Abstract

 Advances in genomic technology make possible the large-scale collection of genomic data for research purposes. Many international initiatives seek to collect genomic data on large populations, often relying on existing collections to populate their databases. As these efforts progress, the debate over whether or not to return individual genetic research results to study participants remains an area of much contention. Some recommend returning results to participants only if the issue was addressed in the original study consent form. Much of the data being used in current studies, however, may have been derived from biospecimens collected years ago with consent documents that did not anticipate the possibility of returning individual level genomic results. We conducted an analysis of informed consent documents from published genome-wide association studies (GWAS) (n=40) to explore whether future research use of biospecimens or data is anticipated, and if return of results is addressed and how it is described to better understand participants’ expectations for future disclosure. The majority (70%) of the GWAS consent documents we analyzed either stated explicitly that individual genomic results would not be returned or were silent on the issue. This has implications for how researchers and members of Research Ethics Committees manage the return of results from sequencing studies using legacy samples and data.

Synchronous Ileal Neuroendocrine Tumor and Ovarian Steroid Cell Tumor Present in a Female With Hyperandrogenism

il·e·um

ˈilēəm/ noun Anatomy noun: ileum; plural noun: ilea

1. the third portion of the small intestine, between the jejunum and the cecum.

                                        ~~~~~~~~~~~~~~~~~~~
 abstract

 Well-differentiated neuroendocrine tumors (NET) of the ileum are generally slow-growing tumors with metastatic potential that may cause systemic symptoms from the secretion of serotonin, cortisol, and other biologically active substances. Likewise, steroid cell tumors of the ovary are slow-growing tumors that cause systemic symptoms from the functional production of androgens, estrogens, and other hormones. To the best of our knowledge, synchronous ileal NET and ovarian steroid cell tumors have not been previously reported in the English literature. We present a case of a 59-yr-old woman with 2 primary tumors that were found incidentally: a Stage III (T2N1M0) 1.6 cm well-differentiated NET (NET G₂) of the terminal ileum with metastasis to a mesenteric lymph node and a 2.4 cm steroid cell tumor of the left ovary. The patient had suffered from hyperandrogenism for several years before diagnosis of an ovarian steroid cell tumor, but had no symptoms attributable to the NET. From review of the literature, this is the first case description of these 2 primaries arising in the same individual.

What It's Like To Have Ovarian Cancer In Your 20s (North Wales)

Ovarian Cancer Signs Twenties (media)

Laparoscopy versus laparotomy for FIGO stage I ovarian cancer - update The Cochrane + plain language summary

abstract:

Background

This is an updated version of the original review that was first published in the Cochrane Database of Systematic Reviews 2008, Issue 4. Laparoscopy has become an increasingly common approach to surgical staging of apparent early-stage ovarian tumours. This review was undertaken to assess the available evidence on the benefits and risks of laparoscopy compared with laparotomy for the management of International Federation of Gynaecology and Obstetrics (FIGO) stage I ovarian cancer.

Objectives

To evaluate the benefits and harms of laparoscopy in the surgical treatment of FIGO stage I ovarian cancer (stages Ia, Ib and Ic) when compared with laparotomy.

Search methods

...... For this update we searched CENTRAL, MEDLINE, and Embase from November 2011 to September 2016.

Selection criteria

Randomised controlled trials (RCTs), quasi-RCTs and prospective cohort studies comparing laparoscopic staging with open surgery (laparotomy) in women with stage I ovarian cancer according to FIGO.

Data collection and analysis

There were no studies to include, therefore we tabulated data from non-randomised studies (NRS) for discussion as well as important data from other meta-analyses.

Main results

We performed no meta-analyses.

Authors' conclusions

This review has found no good-quality evidence to help quantify the risks and benefits of laparoscopy for the management of early-stage ovarian cancer as routine clinical practice.

 

Plain language summary

Laparoscopy versus laparotomy (open surgery) for early-stage ovarian cancer

Background
Stage I ovarian cancer is diagnosed when the tumour is confined to one or both ovaries, without spread to lymph nodes or other parts of the body. Approximately 25% of women with ovarian cancer will be diagnosed at an early stage, thus the diagnosis often occurs due to an accidental finding. The intention of surgical staging is to establish a diagnosis, to assess the extent of the cancer and to remove as much tumour as possible. The latter is particularly important as women with ovarian cancer survive for longer when all visible tumour has been removed.
Review question
We conducted this review in an attempt to clarify whether laparoscopy (keyhole surgery) is as safe and effective as laparotomy (open surgery) for early-stage ovarian cancer. We intended to include only high-quality studies that compared the two types of surgery. We wanted to know whether women having laparoscopy survived as long as those having open surgery and whether there were differences in the time it took for the cancer to get worse. We were also interested to see how these different surgeries compared with regard to blood loss and other complications.
Main Findings and Quality of the Evidence
We search the literature from 1990 to 2016. Unfortunately, we were unable to find any high-quality randomised trials comparing these approaches.

Cytologic studies of the fallopian tube in patients undergoing salpingo-oophorectomy

open access
 

Patient selection

An Institutional Review Board approval was obtained from University of Arizona prior to commencing the study. A total of 38 patients were recruited resulting in 56 fallopian tube specimens. In this study, cells from bilateral fallopian tubes were combined into a single vial to generate one specimen for each of 20 patients. The remaining specimens represented samples from a single fallopian tube. Samples from pregnant women were excluded. Patients’ age ranged from 32 to 86 years old with a mean of 55 years, of whom 26 patients were post-menopausal and 12 patients were pre-menopausal. Informed consent was obtained from each patient.

 Conclusions

In summary, this study shows tubal cytology can distinguish malignant from non-malignant and identify precursor lesions such as STIC. In addition, tubal cytology may help to identify non-malignant proliferative disorders. There is potential utility for tubal cytology in screening women at high risk for ovarian or tubal malignancy prior to bilateral risk reducing salpingo-oophorectomy.

Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care (Lynch Syndrome...)

abstract

Purpose

Genetic evaluation is increasingly becoming an integral part of the management of women with newly diagnosed breast and ovarian cancer (OC), and of individuals at high risk for these diseases. Genetic counseling and testing have been incorporated into oncological care to help and complete management and treatment strategies. Risk assessment and early detection strategies in individuals with BRCA1/2 mutations and with Lynch syndrome have been quite extensively studied, whereas much less is known about the management of mutation carriers with less common high-penetrance cancer susceptibility genes (PTEN, TP53, STK11, CDH1), and particularly those who carry mutations in moderate-penetrance genes (e.g., PALB2, CHEK2, ATM, NF1, RAD51C, RAD51D, BRIP1).

Methods

The latter patient groups represent important ongoing research opportunities to enable informed counseling about appropriate clinical management.

Conclusion

We summarize the current guidelines for the management of high and moderate-penetrance mutations for breast and OC susceptibility. Continuous updating of guidelines for proper clinical management of these individuals is ongoing because of rapid advances in technology and knowledge in this field. Thus, we exhort the use of multigene panels for the assessment of cancer risk beyond the classic predisposition syndromes as a new standard of care in cancer genetics. We further support an increase of genetic counselors in Europe and use of their expertise to support genetic testing in specialist multidisciplinary teams.

Educational and Psychosocial Support Needs in Lynch Syndrome...

abstract:
Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group
 
 Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012. Participant survey data evaluating satisfaction, clarity, and unmet needs for each event were retrospectively analyzed and summarized using descriptive statistics. Annual LSEW attendance ranged from 53 to 75 total participants. LSEW year 1 participants indicated a need for a support group, and preferred in-person meetings at a frequency of every 3-6 months. For LSEW year 2-5 participants, >96 % reported satisfaction with the LSEW, and >82 % expressed interest in secure online support. Common themes for improvement included increased time for question and answer sessions and additional introductory genetics education. Responding LSPAN participants (n = 57 total survey responses in 11 meetings) found the meetings helpful (100 %), information clear (91 %), and presence of a genetic counselor useful (67 %). Desired discussion topics included coping with stress and anxiety, development of a support network, family communication about LS, genetic testing decisions, and bereavement. Following genetic counseling, a need exists for ongoing educational and emotional support in LS. Implementation of resources such as the LSEW and LSPAN is feasible and perceived as helpful by participants.

Detecting OVarian cancer Early McGill University

McGill University
 Detecting OVarian cancer Early

The DOVE project (Detecting OVarian cancer Earlier) is a clinical research study aimed at discovering a method of detecting ovarian cancer at an early stage. This cancer is referred to as a "silent killer" because in its early stages its symptoms are vague and non-specific. Therefore it mimics many common benign diseases and is therefore ignored by patients and doctors alike.
If detected early (stage I) ovarian cancer (OC) is curable by surgery alone in over 90% of the cases. Over 70% of women are diagnosed in stage III or IV, when despite extensive surgery and chemotherapy, over 50% will relapse within two years, and more than 80% will die of disease within 5 years.
Objectives:

1. To determine whether the presence of a fast tracking open access dedicated diagnostic center will increase the proportion of women diagnosed at early stages where they are curable.
2. To inform and educate the public and primary care doctors about the symptoms of ovarian cancer and the appropriate diagnostic investigations
3. To develop the probability tool that will accurately identify the particular cluster of symptoms that suggest that the probability of OC is high in a particular symptomatic woman

Method:
Women over 50 year-old, symptomatic for more than 2 weeks and less than one year are eligible and no referrals are necessary. They are assessed by physical examination, endovaginal ultrasound and serial blood test, CA-125 to rule in or rule out ovarian cancer.
Funded by: Canadian Institute of Health Research (CIHR), McGill University Health Centre Foundation, Royal Victoria Hospital Foundation and the Montreal General Hospital Foundation
Principal Investigator: Dr Lucy Gilbert (MUHC) profileCo-Investigators: Dr S Krishnamurthy profile, Dr I Karp, Dr M Tremblay, Dr P Gauthier, Dr JSampalis profile, Dr J Takefman profile
Refer women to the DOVE project at 1-866-716-3267 to schedule an appointment for ovarian cancer diagnostic testing.

Estimating the Prevalence of Ovarian Cancer Symptoms in Women Aged 50 Years or Older: Problems and Possibilities

abstract:
Estimating the Prevalence of Ovarian Cancer Symptoms in Women Aged 50 Years or Older: Problems and Possibilities

 Diagnostic testing is recommended in women with “ovarian cancer symptoms.” However, these symptoms are nonspecific. The ongoing Diagnosing Ovarian Cancer Early (DOVE) Study in Montreal, Quebec, Canada, provides diagnostic testing to women aged 50 years or older with symptoms lasting for more than 2 weeks and less than 1 year. The prevalence of ovarian cancer in DOVE is 10 times that of large screening trials, prompting us to estimate the prevalence of these symptoms in this population. We sent a questionnaire to 3,000 randomly sampled women in 2014–2015. Overall, 833 women responded; 81.5% reported at least 1 symptom, and 59.7% reported at least 1 symptom within the duration window specified in DOVE. We explored whether such high prevalence resulted from low survey response by applying inverse probability weighting to correct the estimates. Older women and those from deprived areas were less likely to respond, but only age was associated with symptom reporting. Prevalence was similar in early and late responders. Inverse probability weighting had a minimal impact on estimates, suggesting little evidence of nonresponse bias. This is the first study investigating symptoms that have proven to identify a subset of women with a high prevalence of ovarian cancer. However, the high frequency of symptoms warrants further refinements before symptom-triggered diagnostic testing can be implemented.

Teen With Ovarian Cancer Possibly Youngest In U.S. (stage 1V age 16)

 CBS Denver

Quality of life after cancer—How the extent of impairment is influenced by patient characteristics

open access
  Table of Contents

• Abstract
• Background
• Methods
• Results
• Discussion
• Conclusion
• Declarations
• References

 The implementation of efficient networks of (ambulant) health-care providers (primary care physicians, clinical oncologists, nurse practitioners, mental health professionals) is urgently needed, in particular since the number of cancer survivors is steadily increasing and many of them have or will have multiple impairments.

As gene-editing advances, a geneticist turns to the faithful

science news

Geneticist Ting Wu (Harvard Medical School) wants to improve the public’s understanding of genetics.

Clear cell carcinomas of the ovary: a mono-institutional study of 73 cases in China......

open access:
Clear cell carcinomas of the ovary: a mono-institutional study of 73 cases in China with an analysis of the prognostic significance of clinicopathological parameters and IMP3 expression
 

IMP3 immunohistochemical staining and survival

Forty-six of the 73 cases (63 %) showed positive IMP3 expression (Fig. 2a and 2b), and the remaining 27 cases (37 %) were IMP3 negative.

 The importance of IMP3 expression in the female reproductive system is controversial. One study suggested that IMP3 was a prognostic marker in metastatic ovarian cancer [35], Kobel et al. suggested that IMP3 expression was an independent indicator of a poor ovarian CCC prognosis [12], and Noske et al. suggested that IMP3 expression was a marker of a good prognosis in ovarian cancer (including serous carcinoma and non-serous carcinoma) [15]. No further reports regarding IMP3 as a prognostic biomarker have been published. ...

 Conclusion
In conclusion, we demonstrated that tumor stage and IMP3 expression are prognostic indicator in ovarian CCC. IMP3 overexpression is a potential marker of poor prognosis for ovarian CCC, even in stage I. More studies are required to further clarify the mechanism of IMP3 expression and its significance in ovarian CCC

The effects of metformin on ovarian cancer: an updated systematic review and meta-analysis

open access updated review September 30, 2016

In conclusion, the present study suggests that metformin exposure is associated with reduced risk of ovarian cancer and has a tendency to improve survival in female patients with diabetes. Well-designed randomized clinical trials are needed to further confirm the findings.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gyn Cancer Risk.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

 Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.

Early onset breast cancer in Ashkenazi women carriers of founder BRCA1/2 mutations: beyond 10 years of follow-up. - PubMed - NCBI

abstract (Israel)

 This study uncovers disease characteristics by long-term follow-up in Ashkenazi early onset breast cancer (EOBC) patients, carriers of founder BRCA1/2 mutations compared to non-carriers of such mutations. An archives-retrospective design was conducted to study the pathological and clinical characteristics of 149 Ashkenazi Jewish EOBC patients (<42 years) who were referred consecutively to the oncogenetic clinic by the oncology centre at Rambam HealthCare Campus, as from 1995, with a mean follow-up of 13.61 years. Of 149 patients, 33 (22.1%) and 15 (10.1%) carried the founder BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) mutations, respectively; and 101 (67.8%) were non-carriers of these mutations. Contralateral breast-cancer was predominant among BRCA1/2 carriers compared to non-carriers (14, 58.3%; 6, 60%; 7, 8.1%; respectively, p < .001). Ovarian cancer was diagnosed in two BRCA1 carriers and one non-carrier. Oestrogen and/or progesterone receptor negative tumours were majorly detected in BRCA1 carriers (n = 16, 57.1%) compared to BRCA2 carriers (n = 4, 30.8%) and non-carriers (n = 23, 25.3%) (p = .007). BRCA1 carriers and non-carriers developed contralateral breast cancer at an earlier age than BRCA2 carriers. BRCA2 carriers portrayed similar tumour characteristics to non-carriers. EOBC BRCA1/2 carriers are at risk to develop bilateral disease; however, they are similarly susceptible for local recurrence, distant metastases and mortality.

All your data (effectively) belong to us: data practices among direct-to-consumer genetic testing firms

Abstract: Genetics in Medicine

Funder

Cancer Care Ontario, Ontario Institute for Cancer Research

 Conclusion:

Our analysis shows that DTC-GT companies do not consistently meet international transparency guidelines related to confidentiality, privacy, and secondary use of data.

Should patients be allowed to opt out of routine genetic testing of colorectal tumors?

press release

TORONTO, Oct. 6, 2016--Health-care providers support routine testing of colorectal tumours to identify more individuals who have the most common genetic condition responsible for such cancers, a new study suggests.
And few felt patients should have the right to opt out of this test that would determine whether they have Lynch Syndrome, according to the study by Dr. Yvonne Bombard, a genomics and health services researcher in the Li Ka Shing Knowledge Institute of St. Michael's Hospital.
The study was published online today in the journal Genetics in Medicine.....

 Dr. Bombard interviewed surgeons, genetic counselors, oncologists, primary care physicians and gastroenterologists for their views and experiences on tumor testing, notification of results, counseling patients with Lynch Syndrome and their families, and their vision for the design and implementation of routine testing.

abstract: Universal tumor screening for Lynch syndrome: health-care providers’ perspectives

(Ca-125) Counting to 125: The Painstaking Journey to a Landmark Ovarian Cancer Biomarker

The Painstaking Journey to a Landmark Ovarian Cancer Biomarker

(repost) Ovarian carcinoma diagnosis: the clinical impact of 15 years of change

British Journal of Cancer - Open access

Precision Medicine: Current Status and Near-Term Implications (Part 2)

video (7:47 min)

Dr. Haffizulla: Thank you for joining us for this PracticeUpdate. I’m Dr. Farzanna Haffizulla. I am here with Dr. Axel Grothey. Dr. Grothey is a consultant in the Division of Medical Oncology at the Mayo Clinic. He’s also a professor of oncology in clinical and translational science. Again, we’re so happy to have you here today.
Dr. Grothey: Thank you for having me.
Dr. Haffizulla: How are new technologies, such as circulating tumor DNA–based assays, changing the way we consider primary and secondary drug-resistance mechanisms?....

Home - ClinicalTrials.gov Locations of Recruiting Studies

ClinicalTrials.gov

 Locations of Recruiting Studies

	Non-U.S. only (56%)
	U.S. only (39%)
	Both U.S. and non-U.S. (5%)

Total N = 39,935 studies
(Data as of October 10, 2016)

• See more trends, charts, and maps

Power to the people: To what extent has public involvement in applied health research achieved this? (UK)

Power to the people: To what extent has public involvement in applied health research achieved this? | Research Involvement and Engagement | Full Text

  The public involved in research are not always equal partners. The scientific research community still has the loudest voice and patients and the public do not always feel sufficiently empowered to challenge it.

  There is also concern that the public representatives on funding panels are drawn from a small pool of people (often with a health or research background) and are not very representative of the general population [33]. There is evidence that as they become familiar with the working practices and conduct of panels and receive training they become ‘professionalised’ and adopt a professional rather than a lay discourse [53]. Whilst this may serve to enhance their credibility and influence on scientific committees, it inevitably involves a loss of ‘freshness’ and an increase in their alignment to the researcher view. A study of this process among people with experience of cancer who were involved with research panels noted that there were “no examples of individuals criticizing or challenging the dominant scientific model” [53] p.615.

Characteristics and outcome of recurrence in molecularly defined adult-type ovarian granulosa cell tumors

abstract

Highlights

•

Tumor rupture is the strongest predictive factor for AGCT recurrence.

•

AGCT requires active follow up for ten to fifteen years after primary diagnosis.

•

Recurrences may develop asymptomatically and in multiple anatomical locations.

•

Recurrences significantly increase disease-related mortality.

---

Objective

Adult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence.

Methods

We identified all patients diagnosed with AGCT during 1956–2014 in Helsinki University Hospital, with a minimum follow-up of one year (n = 240). After a histological review supplemented with FOXL2 (402C-G) mutation status analysis, we analyzed the clinical data for association with relapse.

Results

The final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5 years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4 years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3 years. Premenopausal status at initial diagnosis, FIGO stage Ic versus Ia, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGCT in a median time of 15.3 years.

Conclusion

Tumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15 years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations.

Non-epithelial Ovarian Cancer: Elucidating Uncommon Gyn Malignancies

open access

Non-epithelial ovarian cancers (NEOC) are a group of fascinating but uncommon malignancies which can be extremely challenging to treat. Collectively, these tumours only represent 10-15% of all ovarian cancers and occur in all age groups from childhood to old age. This broad term includes diverse tumours of germ cell origin, sex cord-stromal cell origin, as well as extremely rare types of ovarian cancer, such as small-cell carcinomas and sarcomas, each of which require specialist management. It is imperative that these rare tumours are managed with accurate diagnosis, staging and treatment in order to optimize patient outcomes. The aetiology and molecular origins of each sub-group of NEOC remain poorly understood and international cooperation to facilitate high quality translational research is needed. This review summarizes the published literature on the incidence, clinical presentation, pathology, therapeutic interventions, survival and prognostic factors of each sub-type of NEOC.

• Germ cell tumours
• sex cord-stromal tumours
• review

The Supplement Paradox: Negligible Benefits, Robust Consumption

JAMA open access

Calcium supplements could increase risk of heart disease, new study finds

Baltimore Sun

 "We think the body metabolizes supplements and dietary calcium differently," said Dr. Erin Michos, associate director of preventive cardiology and associate professor of medicine at the Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins University School of Medicine. "If you are worried about your bones, then get your calcium through food."

                                ~~~~~~~~~~~~~~~~~~~~~~~~~~
 

• Original Research
  • Epidemiology

open access:

Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10‐Year Follow‐up of the Multi‐Ethnic Study of Atherosclerosis (MESA)  

Don't Ask Me To 'Get Over' My History With Breast Cancer (or any other cancer)

Huffington Post

NCI summaries - Updates (recent0

PDQ Updates for Health Professionals

 National Cancer Institute sent this bulletin at 10/11/2016 07:59 AM EDT

You are subscribed to PDQ Updates for Health Professionals from the National Cancer Institute. NCI newly published or updated these health professional summaries within the last week.

• Breast Cancer Prevention
• Cancer Genetics Overview
• Cancer Genetics Risk Assessment and Counseling
• Cancer Screening Overview
• Genetics of Breast and Gynecologic Cancers
• Genetics of Colorectal Cancer
• Lung Cancer Screening
• Prostate Cancer Screening

Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis (BRCA2)

syn·chro·nous

ˈsiNGkrənəs/ adjective adjective: synchronous

1.

existing or occurring at the same time.

                              ~~~~~~~~~~~~~~~~~~~
open access

We report here the case of a woman with a germline BRCA2 mutation who presented with synchronous onset of breast cancer and pancreatic cancer.

 To our knowledge, simultaneous onset of both breast and pancreatic cancer has never been reported in the BRCA literature or any other case report before.

 

Paraneoplastic Syndromes: Background, Pathophysiology, Etiology

medscape

Case Report: Syndrome of Inappropriate Antidiuretic Hormone and Tumor Lysis in Ovarian Cancer

 Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease.


open access

This is a case report describing 2 rarely described paraneoplastic syndromes that not only occurred in the same patient, but also in a malignancy with which the syndromes are rarely associated—ovarian cancer.

 An extensive literature search revealed only one other case of newly diagnosed ovarian cancer with SIADH.⁴

Tumor lysis syndrome (TLS) is a serious and potentially life-threatening adverse event caused by massive lysis of tumor cells as a consequence of chemotherapy treatment, but can also occur spontaneously in certain malignancies. Although rare in solid tumors, it is more commonly associated with hematologic malignancies. Associated clinical and laboratory derangements include acute renal injury, cardiac arrhythmias, seizures, and electrolyte abnormalities such as hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia.