Hormone Replacement Therapy for Ovarian Cancer - NCI + Commentary

HRT

Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status

abstract
 

OBJECTIVES:

After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors.

METHODS:

We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10years for a range of factors including BRCA mutation status and extent of residual disease post-surgery.

The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer

open access

 Statement by the Kommission Ovar of the AGO: The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer

 Introduction

• The New FIGO Classification
• Stage I
• Stage II
• Stage III
• Stage IV
• The New WHO Classification
• Serous tumors
• Mucinous tumors
• Seromucinous tumors
• Endometrioid tumors
• Clear cell tumors
• Brenner tumors
• References

sample excerpt:
 Clear cell tumors
The new WHO classification has not resulted in any significant changes in the classification of clear cell tumors. Clear cell BOTs are very similar to clear cell adenomas and parts of both entities are usually present in tumors. In contrast, clear cell carcinomas are irregular, with papillary structures, solid parts with desmoplastic hyalinized stroma, and high-grade nuclear atypia [22]. Clear cell carcinomas may be associated with Lynch syndrome but also with endometriosis and are the most common ovarian carcinoma with paraneoplastic symptoms (thromboembolism and hypercalcemia) [24], [25].

Navigating Female Hormones: A Pharmacist's Guide to HRT

Medscape (print preview page)

Estrogen Excess

Decrease in sexual interest Depression Fibrocystic breasts Heavy menses Uterine fibroids Weight gain

Estrogen Deficiency

Difficulty losing weight Fatigue/declining energy Infertility Thinning hair, skin, nails Vaginal dryness Weight gain around middle

Progesterone Excess

Bladder incontinence Glucose intolerance/insulin resistance Relaxed ligaments Suppressed immune system

Progesterone Deficiency

Anxiety/depression Insomnia Irritability Osteoporosis Weight gain

Testosterone Excess

Acne Anxiety, anger, agitation Hair loss/male-patterned hair growth Infertility Insulin resistance Weight gain

Testosterone Deficiency

Decline in muscle tone Decreased sex drive Fatigue Headache Thin lips/saggy cheeks Trouble reaching climax

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer

abstract

BACKGROUND

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer.

METHODS

Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing.

RESULTS

Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas).

CONCLUSIONS

In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers.

Surgical management of ovarian carcinoma metastatic to the breast and axilla: A role for metastasectomy?

abstract

 As patients with ovarian cancer are living longer, surgeons will be faced with the management of metastatic lesions amenable to resection more frequently. We present two patients with ovarian cancer metastatic to the breast who underwent resection for their metastases, but their outcomes differed significantly. After reviewing the literature, we propose that there can be definite benefit to resection in the appropriately selected patients and discuss factors to consider prior to proceeding with surgery.

Childhood cancers in families with and without Lynch syndrome

abstract

Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-deficient colorectal cancer (non-Lynch syndrome families). There was no evidence of a difference in the proportion of relatives with a childhood cancer between Lynch syndrome families (41/17,230; 0.24 %) and non-Lynch syndrome families (179/94,302; 0.19 %; p = 0.19). Incidence rate of all childhood cancers was estimated to be 147 (95 % CI 107–206) per million population per year in Lynch syndrome families and 115 (95 % CI 99.1–134) per million population per year in non-Lynch syndrome families. There was no evidence for a significant increase in the risk of all childhood cancers, hematologic cancers, brain and central nervous system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families.

Familial Cancer - Index - December issue

Familial Cancer

Are We Closer to Preventing Ovarian Cancer? + Viewpoint

medscape

Improving the management of post-operative acute pain: priorities for change

open access

...Poor management in the case of post-operative acute pain can contribute to medical complications such as pneumonia, deep vein thrombosis, infection, chronic pain and depression7^,8. It is also one of the three most common medical causes of delayed discharge after ambulatory surgery9. In addition to the significant personal suffering and social burden that result, considerable financial expense is incurred, both directly in extra healthcare costs and indirectly as a result of absenteeism, lost production and welfare payments. All post-operative acute pain should therefore be prevented if possible or, if not, accurately diagnosed and then treated promptly and effectively to improve patient comfort, avoid complications, prevent the development of chronic pain, and reduce the economic burden on society10. However, despite the numerous guidelines on managing acute pain produced over the past two decades11–14, the proven benefits of the ‘pain-free hospital’ initiative15 and the many effective analgesics now available, surveys suggest that for many patients there has been little improvement over this period16–18.....

open access: Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA

Blogger's Note: see tables for additional detailed information

JAMA Oncology - open access

 Conclusions and Relevance  Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.

 .....In some patients, a cancer-predisposing variant is present in the “normal” DNA, either inherited or as an early postzygotic event. The burden of germline variants differs by tumor type, although it can be substantial (eg, mutations of the Fanconi pathway genes can be seen in 20% of patients with ovarian cancer).⁶ Most germline susceptibility variants are not targetable, although there are exceptions (eg, PARP inhibitors in patients with BRCA1 and BRCA2 mutation-associated cancers). Efforts to characterize germline susceptibility are therefore usually ancillary to the primary purpose of clinical tumor mutation profiling. However, knowledge of these variants could guide the preventive care of the patient or the patient’s family, even if the knowledge does not influence the treatment of the patient’s cancer.^7....

At a Glance

• Targeted tumor sequencing with a panel of 341 genes and matched normal DNA in 1566 individuals with advanced malignant neoplasms revealed presumed pathogenic germline variants (PPGVs) in about 16% of individuals.
• Most PPGVs (80.5%; 95% CI, 75.1%-85.0%) were in genes related to cancer susceptibility.
• The PPGVs in genes previously designated as clinically actionable were seen in 5.0% (95% CI, 4.1%-6.2%) of individuals.
• Most cancer-susceptibility PPGVs were retained in the tumor (91.9%; 95% CI, 87.3%-95.0%).
• Almost all individuals carried germline variants of uncertain significance that will require significant curation to determine clinical significance.
  

  
  

  Supplement.

  eTable 1. Distribution and demographics of cases across 68 cancer types (n=1566)

  eTable 2. Genes on MSK-IMPACT (n=341)

  eTable 3. Summary of OMIM annotated genes on MSK-IMPACT compared by modes of inheritance

  eTable 4. OMIM genes and associated syndromes on MSK-IMPACT panel

  eTable 5. Presumed pathogenic germline variant classifications in OMIM genes (including Cancer and ACMG gene subsets) included on MSK-IMPACT

  eTable 6. Genes with variant totals for single nucleotide variants, insertion or deletions, and copy number variants (SNV, Indels, CNVs) grouped by potential phenotype in the patient

  eTable 7. Presumed pathogenic germline variants in OMIM genes (including Cancer and ACMG gene subsets) included on MSK-IMPACT per subject

  eTable 8. Presumed pathogenic germline variants in OMIM genes and status of PPGV in tumor

  eTable 9. Aggregate presumed pathogenic germline variant totals by disease site and gene

  Supplemental Content

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In Flanders Fields

"In Flanders Fields" (ref. Wiki) is a war poem in the form of a rondeau, written during the First World War by Canadian physician Lieutenant-Colonel John McCrae. He was inspired to write it on May 3, 1915, after presiding over the funeral of friend and fellow soldier Alexis Helmer, who died in the Second Battle of Ypres. According to legend, fellow soldiers retrieved the poem after McCrae, initially dissatisfied with his work, discarded it. "In Flanders Fields" was first published on December 8 of that year in the London-based magazine Punch.
It is one of the most popular and most quoted poems from the war. As a result of its immediate popularity, parts of the poem were used in propaganda efforts and appeals to recruit soldiers and raise money selling war bonds. Its references to the red poppies that grew over the graves of fallen soldiers resulted in the remembrance poppy becoming one of the world's most recognized memorial symbols for soldiers who have died in conflict. The poem and poppy are prominent Remembrance Day symbols throughout the Commonwealth of Nations, particularly in Canada, where "In Flanders Fields" is one of the nation's best-known literary works. The poem also has wide exposure in the United States, where it is associated with Memorial Day.....
  
Poem

 

An autographed copy of the poem from In Flanders Fields and Other Poems. Unlike the printed copy in the same book, McCrae's handwritten version ends the first line with "grow".

 

The first chapter of In Flanders Fields and Other Poems, a 1919 collection of McCrae's works, gives the text of the poem as follows:^[9]

In Flanders fields the poppies blow
Between the crosses, row on row,
That mark our place; and in the sky
The larks, still bravely singing, fly
Scarce heard amid the guns below.

We are the Dead. Short days ago
We lived, felt dawn, saw sunset glow,
Loved and were loved, and now we lie
In Flanders fields.

Take up our quarrel with the foe:
To you from failing hands we throw
The torch; be yours to hold it high.
If ye break faith with us who die
We shall not sleep, though poppies grow
In Flanders fields.

QOL and mental health among women with ovarian cancer: examining the role of emotional and instrumental social support seeking

Abstract

 The purpose of the present study was to examine the role of emotional and instrumental social support seeking in the quality of life (QOL) and mental health of women with ovarian cancer. Participants were recruited through the Pennsylvania Cancer Registry, and one hundred women took part in a mail questionnaire that collected information on their demographics, medical status, social support seeking, QOL and mental health including anxiety, depression and stress. Hierarchical linear regression analyses were conducted to assess the influence of emotional and instrumental social support seeking on QOL and mental health. After controlling for remission status, greater emotional social support seeking was predictive of higher overall QOL, social/family QOL, functional QOL and lower depression scores. Instrumental social support seeking was not significant in the models. The results illustrate that social support seeking as a coping mechanism is an important consideration in the QOL and mental health of women with ovarian cancer. Future studies should examine the psychological and behavioral mediators of the relationship to further understand the QOL and mental health of women with ovarian cancer.

CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype

open access
  

ABSTRACT

Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research.

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Querying a gene of interest

CSIOVDB seeks to provide users with the expression profiles of certain genes of interest relevant to ovarian cancer; in particular, the molecular subtype distribution and subtype-specific outcomes in terms of overall survival and disease-free (progression- and recurrence-free) survival......

Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis

Abstract
 

BACKGROUND:

Numerous studies have focused on the association between MMP-12-82A>G polymorphism and cancer risk, but produced inconsistent results. Therefore, we performed a meta-analysis of case-control study to evaluate the association of MMP-12-82A>G polymorphism and cancer risk.

METHODS:

A systematic literature search was conducted among PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI) and Wangfang databases updated on May 1st, 2015. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between this polymorphism and cancer risk.

RESULTS:

A total of seventeen case-control studies with 7,450 cases and 7,348 controls were identified and analyzed. Overall, there was no statistically significant association between MMP-12-82A>G polymorphism and increased risk of cancer under all genetic models. Subgroup analysis by ethnicity observed that there is no strong relationship between MMP-12-82A>G polymorphism and cancer risk among Asian and European populations. Furthermore, stratified analysis based on the source of control revealed no statistically significant association between MMP-12-82A>G polymorphism and cancer risk either in hospital-based or population-based studies. However, when we stratified analysis based on cancer type, significant association was found in ovarian cancer, but not in other types of cancer.

CONCLUSION:

This meta-analysis suggests that MMP-12-82A>G polymorphism is not significantly associated with overall cancer risk. However, MMP-12-82A>G polymorphism may increase the susceptibility to ovarian cancer.