Retraction notice to "M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells" [Gynecol. Oncol. 101 (2006) 108-113]

 Blogger's Note/Opinion: it would be most helpful if the reason for the retraction was included in the notice

Retraction notice 

Gynecol Oncol. 2013 Apr;129(1):270.

[No authors listed]

Retraction of

• Takai N, Ueda T, Nishida M, Nasu K, Narahara H. Gynecol Oncol. 2006 Apr;101(1):108-13.

Identification of Novel Variants in Colorectal Cancer Families by High-Throughput Exome Sequencing

Abstract

 Impact: Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk.

Underestimated survival predictions of the prognostic tools Adjuvant! Online and PREDICT in BRCA1-associated breast cancer patients

Abstract + references

BRCA1-associated breast cancer is considered an unique clinical entity with its own specific histopathological characteristics. Several recently published large studies have shown that overall survival of BRCA1 mutation carriers having breast cancer is similar to sporadic breast cancer patients. It was also suggested that better response to chemotherapy is one of the most important factors that improves the clinical outcome of breast cancers with unfavorable histopathological subtypes in BRCA1 mutation carriers. Adjuvant! Online and PREDICT are web-based prognostic tools that estimate the survival benefit of adjuvant chemotherapy in primary breast cancer patients. These tools have been extensively validated in different populations; however, the accuracy of the predictions made by Adjuvant! Online and PREDICT among BRCA1 mutation carriers has not yet been investigated. In this study we have found, that predictions of overall and breast cancer-specific survival obtained from Adjuvant! Online and PREDICT were significantly lower than the observed survival percentages in the study population [predicted—observed difference for 10–year overall survival: −9.75 %, P < 0.0001 (Adjuvant! Online); −10.21 %, P < 0.0001 (PREDICT)]. Thus this study suggests that Adjuvant! Online and PREDICT should be used with caution in this group of patients.

Variation in ovarian conservation in women undergoing hysterectomy for benign indications

Abstract

OBJECTIVE:

Emerging data suggest that oophorectomy at the time of hysterectomy for benign indications may increase long-term morbidity and mortality. We performed a population-based analysis to estimate the rates of oophorectomy in women undergoing hysterectomy for benign indications.

METHODS:

The Perspective database was used to estimate the rate of ovarian preservation in women aged 40-64 years who underwent hysterectomy for benign indications. Hierarchical mixed-effects regression models were developed to estimate the influence of patient, procedural, physician, and hospital characteristics on ovarian conservation. Between-hospital variation in ovarian preservation also was estimated.

RESULTS:

Among 752,045 women, 348,972 (46.4%) underwent bilateral oophorectomy, whereas 403,073 (53.6%) had ovarian conservation. Stratified by age, the rate of ovarian conservation was 74.3% for those younger than 40 years of age; 62.7% for those 40-44 years of age; 40.8% for those 45-49 years of age; 25.2% for those 50-54 years of age; 25.5% for those 55-59 years of age; and 31.0% for those 60-64 years of age. Younger age and more recent year of surgery had the strongest association with ovarian conservation. The observed patient, procedural, physician, and hospital characteristics accounted for only 46% of the total variation in the rate of ovarian conservation; 54% of the variability remained unexplained, suggesting a large amount of intrinsic between-hospital variation in the decision to perform oophorectomy.

CONCLUSION:

The rate of ovarian conservation is increasing, particularly among women younger than 50 years old. Although demographic and clinical factors influence the decision to perform oophorectomy, there appears to be substantial between-hospital variation in performance of oophorectomy that remains unexplained by measurable patient, physician, or hospital characteristics.

Long-Term Mortality Associated With Oophorectomy Compared With Ovarian Conservation in the Nurses' Health Study

OBJECTIVE:: To report long-term mortality after oophorectomy or ovarian conservation at the time of hysterectomy in subgroups of women based on age at the time of surgery, use of estrogen therapy, presence of risk factors for coronary heart disease, and length of follow-up.
METHODS:: This was a prospective cohort study of 30,117 Nurses' Health Study participants undergoing hysterectomy for benign disease. Multivariable adjusted hazard ratios for death from coronary heart disease, stroke, breast cancer, epithelial ovarian cancer, lung cancer, colorectal cancer, total cancer, and all causes were determined comparing bilateral oophorectomy (n=16,914) with ovarian conservation (n=13,203).
RESULTS:: Over 28 years of follow-up, 16.8% of women with hysterectomy and bilateral oophorectomy died from all causes compared with 13.3% of women who had ovarian conservation (hazard ratio 1.13, 95% confidence interval 1.06-1.21). Oophorectomy was associated with a lower risk of death from ovarian cancer (four women with oophorectomy compared with 44 women with ovarian conservation) and, before age 47.5 years, a lower risk of death from breast cancer. However, at no age was oophorectomy associated with a lower risk of other cause-specific or all-cause mortality. For women younger than 50 years at the time of hysterectomy, bilateral oophorectomy was associated with significantly increased mortality in women who had never used estrogen therapy but not in past and current users: assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50.
CONCLUSIONS:: Bilateral oophorectomy is associated with increased mortality in women aged younger than 50 years who never used estrogen therapy and at no age is oophorectomy associated with increased survival. LEVEL OF EVIDENCE:: I.

Mucinous borderline tumor involving fallopian tube: case report and review of the literature

Open Access

We report the case of a 74-year-old woman with a primary mucinous borderline tumor of the fallopian tube coexisting with an ovarian mucinous borderline tumor. Data were obtained through histopathologic study of the excised surgical specimen. p53, estrogen receptor (ER) and PAX8 expression were evaluated by immunohistochemistry on the available right fallopian tube and ovary. Both the ovarian and fallopian tube borderline ovarian tumors were negative for p53, ER and PAX8. However, the staining pattern highlighted the transition from a normal ciliated cell to neoplastic epithelia in the fallopian tube fimbria. This is the first report to indicate that mucinous borderline tumors may arise from the ciliated cells at the fallopian tube fimbrial epithelia. ER and PAX8 are useful markers in identifying the transition and origination of these tumors.......

Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing (23andMe/Stanford)

open access

Author and article information

 23andMe, Inc., Mountain View, CA, USA

Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown.
Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service^® report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned.
Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral.

A survey of Canadian cancer patients' perspectives on the characteristics and treatment of breakthrough pain

Abstract

OBJECTIVE:

Breakthrough pain is defined as a transient exacerbation of pain that occurs spontaneously or in response to a trigger despite stable and controlled background pain. The purpose of this study was to explore Canadian patients' awareness of and experience with breakthrough pain in cancer (BTPc).

METHODS:

Four Canadian cancer centers participated in a non-interventional survey recruiting cancer patients who experienced breakthrough pain. These patients were asked about their pain, its impact on functioning, current management and interest in new treatments of BTPc.

RESULTS:

Ninety-four Canadian cancer patients participated in this study, with 96 % stating that cancer pain impacted their daily living with over half unable to go to work or shopping. Fifty percent of patients said that an episode of BTPc lasted greater than 60 minutes, with the pain score being on average 7.8/10, impacting normal work (7.2/10) and general activity (7.1/10). Only 35 % of patients were very satisfied with the speed of relief of their medications. Those who did not take their breakthrough pain medication for every episode stated that was because the pain was not always severe (37 %), or they were afraid of becoming tolerant (23 %) or addicted (12 %). Patients stated that the most important features of a new treatment for BTPc were the ability to relieve pain completely (47 %), and quickly (43 %). Patients expressed willingness to try transmucosal products (80 %) or nasal products (59 %).

CONCLUSION:

Breakthrough cancer pain in Canadian cancer patients greatly impacts their daily lives. There is room for improvement in the management of BTPc, and the majority of patients would be willing to try new treatments.

Fibroblast Growth Factor Receptor 2 Expression May Be Involved In Transformation of Ovarian Endometrioma to Clear Cell Carcinoma of the Ovary

Abstract

Objective: The objective of this study was to determine the genes that may be associated with malignant transformation of ovarian endometrioma.

Methods: Endometriotic epithelial cells were isolated from tissues derived from chocolate cyst linings by laser capture microdissection. A Gene Chip Human Genome U133 Plus 2.0 Array was applied to evaluate levels of gene expression in 3 different groups of epithelial cells: epithelial cells of endometrioma, epithelial cells of endometrioma adjacent to clear cell carcinoma, and epithelial cells of clear cell carcinoma. As a validation assay, real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were performed.

Results: Gene expression analysis identified differential expressions among the 3 groups of epithelial cells.

Should Bevacizumab Be Continued After Progression on Bevacizumab (Avastin) in Recurrent Ovarian Cancer?

Abstract

Objective: The optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB).

Methods: We conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included.

Results: Forty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P = 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P = 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P = 0.72).

Editorial: Resolving the Ductal Carcinoma In Situ Treatment Conundrum

Extract (requires paid subscription to view in full)

A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ of the Breast

open access

"This study was performed to determine whether the prospectively defined, 12-gene Oncotype DX DCIS Score (hereafter referred to as the DCIS Score) quantifies local recurrence risk and provides risk information independent of traditional clinical and pathologic characteristics." 

Letter to the Editor - Measures of promptness of cancer diagnosis in primary care

open access

The time-efficiency principle: time as the key diagnostic strategy in primary care

open access

Breast cancer heterogeneity no barrier to predictive testing, study shows

ESMO

...."The study is innovative because it is one of the first to address the question of intratumour heterogeneity. It means that not all the cells from the same tumour have the same characteristics, and if we want to have a clear picture of the tumour biology we should not limit the evaluation of tumour markers to one area of the tumour itself," Dr. Di Leo said..... 

Study reveals magnitude of variation in gene expression measurements within breast cancers

Blogger's Note: while this study is related to breast cancer, the philosophy should be subject to scrutiny in all cancers

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

ESMO press release:
 
"....One important challenge is the fact that many different cell types can be present within a single tumour (known as intratumoural heterogeneity), each with different patterns of gene expression and potentially different sensitivity to drugs.
"Performing these tests with a single biopsy may or may not accurately represent that cancer, depending on intratumoural heterogeneity," explains lead author Dr Rosanna Lau from the University of Texas MD Anderson Cancer Center, US.
A further complication is that some of the variation between test results can arise from technical variations in the testing process, and not by real differences between samples (analytical variance).....
 
"Developing accurate biomarkers that are not subject to real tumour sampling bias is of critical importance. This intricate study will likely be a gold standard by which other studies in this area are measured. Such in-depth analyses will ultimately be essential in the biomarker qualification process," he said."

CYP3A4*22 genotype and systemic exposure affect (Taxol) paclitaxel-induced neurotoxicity

Abstract

Purpose: Paclitaxel is used for the treatment of several solid tumors and displays a high inter- individual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side-effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity.  

Experimental Design: In an exploratory cohort of patients (n=261) treated with paclitaxel, neurotoxicity incidence and severity, pharmacokinetic parameters and pharmacogenetic variants were determined. ....... Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n=239).  

Results: Exposure to paclitaxel (logAUC) was correlated with severity of neurotoxicity (P <0.00001). Female CYP3A4*22 carriers were at increased risk of developing neurotoxicity (P = 0.043) in the exploratory cohort. CYP3A4*22 carrier status itself was not associated with pharmacokinetic parameters (CL, AUC, Cmax, or T>0.05) of paclitaxel in males or females. Other genetic variants displayed no association with neurotoxicity. In the subsequent independent validation cohort, CYP3A4*22 carriers were at risk of developing grade 3 neurotoxicity (odds ratio = 19.1; P = 0.001).  

Conclusions: Paclitaxel exposure showed a relationship with the severity of paclitaxel-induced neurotoxicity. In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. These observations may guide future individualization of paclitaxel treatment.

THE CHEERFUL ONCOLOGIST “This Is My Last Day on Earth”

Cancer Network

Perspective: Discrimination at the Doctor's Office — NEJM

NEJM

"...Fortunately, most physicians take this tradition and their professional obligations seriously, and overt discrimination is rare. Evidence suggests, however, that even medical professionals are susceptible to implicit biases based on race, social class, sex, weight, and myriad other factors that may affect the care they provide.5 Thus, although we should condemn all types of invidious discrimination against patients, we should be particularly vigilant against the sort of subtle discrimination that can fly under the radar. "

wo cases of flesh-eating disease linked to cancer drug Avastin

Blogger's Note/Opinion:  52 cases reported;  important to put this into the context of the total number of patients receiving Avastin; it is possible that these adverse event numbers are under-reported; on the plus side Avastin has been of great benefit to many patients/numerous types of cancer; caution and awareness - as always  (has been seen in ovarian cancer patients (not common) - since its use with a variety of effects (minor/major)

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

Necrotizing fasciitis (/ˈnɛkrəˌtaɪzɪŋ ˌfæʃiˈaɪtɪs/ or /ˌfæs-/) or NF, commonly known as flesh-eating disease or flesh-eating bacteria syndrome,^[1] is a rare infection of the deeper layers of skin and subcutaneous tissues, easily spreading across the fascial plane within the subcutaneous tissue.
Necrotizing fasciitis is quickly progressing, having greater risk of developing in the immunocompromised due to conditions like diabetes, cancer, etc. It is a severe disease of sudden onset and is usually treated immediately with high doses of intravenous antibiotics. ^[2]........

^{~~~~~~~~~~~~~~~~}

media

 TORONTO — Health Canada is warning that the cancer drug Avastin has been linked in rare cases to necrotizing fasciitis, the fast-moving bacterial infection also known as flesh-eating disease.
Two Canadians taking Avastin developed necrotizing fasciitis and one of them died, the federal department said Thursday in a warning issued in conjunction with the drug's manufacturer, Hoffmann-La Roche Ltd.
The U.S. Food and Drug Administration published a similar warning in mid-March, indicating that cases of the tissue-destroying infection have mainly been seen in people with wound-healing complications or certain internal bleeding conditions.A  safety review of the drug by Roche identified 52 cases of necrotizing fasciitis reported worldwide between November 1997 and September 2012; 17 of them were fatal, including the one Canadian."...........

5 Facts Everyone Should Know About Ovarian Cancer | World Ovarian Cancer Day - May 8th

World Ovarian Cancer Day



Fact 1: All women are at risk for ovarian cancer
Fact 2: Awareness of the early warning signs of the disease may save lives
Fact 3: Diagnosis at an early stage vastly improves a woman’s chance of survival
Fact 4: Ovarian cancer is often diagnosed at a late stage
Fact 5: Many women mistakenly believe a cervical smear test (or Pap test) will detect ovarian cancer. 

Non-equivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations

open access

Interview with Dr. Wong-Rieger Genomics Blog - Drug Patents Important to Protect Patients

Drug Patents Important to Protect Patients

 As you'll hear in this interview with her, she is passionate about patient rights, in particular when it comes to health care and drug access issues.

Clinical Oncology News - Maximizing Novel Technologies

Markman

Clinical Oncology News - Palliative Care Misunderstandings ‘Astonishingly High’

Clinical Oncology News