paywalled: Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort - Gierach - 2011 - International Journal of Cancer - Wiley Online Library

Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort  - International Journal of Cancer 

"These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis."

UK: Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]

Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]

Verified by: Cancer Research UK, April 2012

First Received: April 25, 2012 | Last Updated: April 25, 2012 | Phase: Phase 1 | Start Date: April 2012

Overall Status: Not yet recruiting | Estimated Enrollment: 40

The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours...

Brief Summary

Official Title: “A Cancer Research UK Phase I First in Man Study of the Novel AGC Kinase Inhibitor AT13148 Given Orally in Patients With Advanced Solid Tumours.”

The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours.

• Study Type: Interventional
• Study Design: Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: October 2015

Detailed Clinical Trial Description

AT13148 is a new drug which looks promising in laboratory studies. We now wish to find out if it will be useful in treating patients with cancer. AT13148 is a type of drug called a protein kinase inhibitor. It blocks several different chemical messengers (enzymes) called AGC kinase proteins. These chemical messengers are part of the signaling process within cells which can make cells produce chemicals that trigger and control cell growth and cell death. In some types of cancer these chemical messengers are 'switched on' or 'switched off' permanently due to changes in the genes of cells called "gene mutations" leading to uncontrolled cancer cell growth. AT13148 targets multiple protein kinases from three families of kinases unlike many of the other protein kinase inhibitors currently being tested which target just one or two kinases. This may mean that it will work better and in a wider group of cancer patients. Patients will not be selected to take part based on having these gene mutations for this first trial because we want to learn more about which mutations are most important but this would be the hope for future trials. The patient population anticipated to benefit from this drug includes certain types of breast, prostate and ovarian cancer which more commonly have these gene mutations.

26 APR 2012 - Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians - Wiley Online Library

Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians 

".... After receiving a diagnosis of cancer, survivors soon find there are few clear answers to even the simplest questions, such as: Should I change what I eat? Should I exercise more? Should I gain or lose weight? Should I take dietary supplements? Cancer survivors receive a wide range of advice from many sources about foods they should eat, foods they should avoid, how they should exercise, and what types of supplements they should take, if any. Unfortunately, this advice is often inconsistent and not supported by data...."

Ovarian Cancer

Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States.4 Symptoms tend be nonspecific, making early detection difficult. Consequently, most ovarian cancers are diagnosed at an advanced stage when the prognosis is poor, with an overall 10-year survival rate of 39%.4 The role of lifestyle factors in ovarian cancer prognosis is largely unknown.138, 242 To our knowledge, only 3 studies139, 140, 243 have evaluated the role of dietary factors in ovarian cancer survival. These 3 studies were based on prospective follow-up of the cases participating in case-control studies and evaluated the association between prediagnosis dietary intake and mortality outcomes. One study, conducted in China, focused on the role of green tea and reported that a higher frequency and quantity of green tea intake after diagnosis was associated with better survival.243 The other 2 studies, conducted in Australia140 and the United States,139 suggested that prediagnosis dietary intake may influence the survival experience of patients with ovarian cancer. Both studies tended to support the association of fruit and vegetable consumption with better survival. Dairy food intake was associated with poorer survival in one of the studies,140 while in the other, only milk consumption and not total dairy food consumption was inversely associated with survival.139 Meat consumption was associated with better survival in the Australian study,140 and with lower survival in the study conducted in the United States.139 While these studies controlled for most relevant covariates, they did not include treatment information. In addition, these studies did not evaluate dietary intake after diagnosis. However, they do suggest that dietary intake may influence ovarian cancer survival and warrant further research in this area.

Only one study, also following cases in a case-control study for mortality, has evaluated the role of physical activity in ovarian cancer survival.244 Prediagnosis physical activity was ascertained as hours per week for 3 life periods (childhood, between ages 18-30 years, and in recent years). The study also evaluated the role of changes in physical activity over time. There was not much indication of an association with survival for any of these variables, except for physical activity at aged 18 to 30 years, which seemed to be associated with better survival for women with early stage ovarian cancer and with worse survival for women with an advanced stage of disease at diagnosis.245

The relationship between excess weight and ovarian cancer survival has been evaluated by relatively few studies. Obesity may affect ovarian cancer survival by having a negative impact on optimal surgical and cytotoxic treatment and increasing the likelihood of postoperative complications.246 Overall, the literature evaluating the association between weight/BMI and ovarian cancer survival is limited and inconclusive.76, 242 Cohort studies evaluating the role of prediagnosis obesity obtained at baseline on ovarian cancer mortality have generally found elevated ovarian cancer mortality among obese women.234, 247 Other studies evaluating the role of prediagnosis BMI on ovarian cancer survival by following cases in a case-control study or clinical trial (using baseline data) have offered conflicting results.242 The role of postdiagnosis body size and weight changes on ovarian cancer survival is largely unknown. Only one study has reported on weight changes during chemotherapy and ovarian cancer survival and found that, among patients with advanced ovarian cancer, weight loss during chemotherapy was associated with worse prognosis; however, it is difficult to determine whether this weight loss was involuntary or intentional.248

In summary, while the current evidence is limited and inconclusive, it points to a possible role of dietary factors, physical activity, and body size and weight changes in modulating ovarian cancer survival, and for physical activity in improving the quality of life among ovarian cancer survivors. Further studies are needed before public health recommendations can be made.

paywalled: Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis

Blogger's Note/Opinion: as per abstract, to date and studies over decades, have not found a link between coffee/tea/ovarian cancer risk - so, the question is this: how many more studies will it take to finally put this issue to rest? Unless there are novel (new) findings then we need to move forward.

Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis

Abstract

Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). 

Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. 

Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. 

Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% CI: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. 

Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer.

paywalled: Systematic review of progesterone use by midlife and menopausal women

Systematic review of progesterone use by midlife and menopausal women: Publication year: 2012

Source: Maturitas

 Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception. Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.

Seth's Blog: Don't expect applause

Don't expect applause:

Accept applause, sure, please do.

But when you expect applause, when you do your work in order (and because of) applause, you have sold yourself short. That's because your work is depending on something out of your control. You have given away part of your art. If your work is filled with the hope and longing for applause, it's no longer your work--the dependence on approval has corrupted it, turned it into a process where you are striving for ever more approval.

Who decides if your work is good? When you are at your best, you do. If the work doesn't deliver on its purpose, if the pot you made leaks or the hammer you forged breaks, then you should learn to make a better one. But we don't blame the nail for breaking the hammer or the water for leaking from the pot. They are part of the system, just as the market embracing your product is part of marketing.

"Here, here it is, it's finished."

If it's finished, the applause, the thanks, the gratitude are something else. Something extra and not part of what you created. To play a beautiful song for two people or a thousand is the same song, and the amount of thanks you receive isn't part of that song.

medical news: Study confirms overuse of blood transfusions during surgery

Study confirms overuse of blood transfusions during surgery


"Citing the lack of clear guidelines for ordering blood transfusions during surgery, Johns Hopkins researchers say a new study confirms there is still wide variation in the use of transfusions and frequent use of transfused blood in patients who don't need it.
The resulting overuse of blood is problematic, the researchers say, because blood is a scarce and expensive resource and because recent studies have shown that surgical patients do no better, and may do worse, if given transfusions prematurely or unnecessarily. "Transfusion is not as safe as people think," says Steven M. Frank, M.D., leader of the study described in the journal Anesthesiology.....

Correspondence: Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM

Blogger's Note:  correspondence/author's reply/references; while this is specific to Avastin/breast cancer,  future trial protocols may take note

Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM

PLoS ONE: Effect of Angiogenesis Inhibitor (Avastin) Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature

 Blogger's Note: indicates which cancer patients did/did not show PFS/OS; limited to combo therapies (lack of monotherapy trials); read limitations to the analysis (eg. individual patient data/meta-analysis...); notes serious side effects

PLoS ONE: Effect of Angiogenesis Inhibitor Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature

paywalled: Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.

Abstract

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.

open access: Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review

Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review

Obstetrics and Gynecology International
Volume 2012 (2012), Article ID 953937, 11 pages
doi:10.1155/2012/953937 Review Article Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review

• Abstract
• Introduction
• Methods and Materials
• Results and Discussion
• Options for Fertility Preservation
• Additional Considerations
• Pregnancy after Cancer

Conclusions 

Given the relatively high incidence of cancer in reproductive age women and improvements in 5-year survival, an increasing number of women are presenting for discussion of fertility preservation and pregnancy after cancer treatment. The ASCO published recommendations in 2006 on fertility preservation in cancer patients. These guidelines state that oncologists should address the possibility of infertility with cancer patients and be prepared to discuss possible fertility preservation options or refer the patient to a reproductive specialist. Part of the difficulty in counseling patients regarding the risk of infertility and/or subsequent pregnancy complications is that the risks are dependent on several factors. These risks include the dose and duration of treatment, other risk factors for infertility, the age of the patient, and the patient’s baseline ovarian reserve at the time of initiation of treatment.

paywalled: Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.

Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.

Breast Cancer Res Treat. 2012 Apr 18;

Abstract
The genetic component of breast cancer predisposition remains largely unexplained. Candidate gene case-control resequencing has identified predisposition genes characterised by rare, protein truncating mutations that confer moderate risks of disease. In theory, exome sequencing should yield additional genes of this class. Here, we explore the feasibility and design considerations of this approach. We performed exome sequencing in 50 individuals with familial breast cancer, applying frequency and protein function filters to identify variants most likely to be pathogenic. We identified 867,378 variants that passed the call quality filters of which 1,296 variants passed the frequency and protein truncation filters. The median number of validated, rare, protein truncating variants was 10 in individuals with, and without, mutations in known genes. The functional candidacy of mutated genes was similar in both groups. Without prior knowledge, the known genes would not have been recognisable as breast cancer predisposition genes. Everyone carries multiple rare mutations that are plausibly related to disease. Exome sequencing in common conditions will therefore require intelligent sample and variant prioritisation strategies in large case-control studies to deliver robust genetic evidence of disease association.

blogger: Hospitals, Practice Administrators and Clinicians: You Gotta Learn to Love Patient Ratings – Health Affairs Blog

Hospitals, Practice Administrators and Clinicians: You Gotta Learn to Love Patient Ratings – Health Affairs Blog

paywalled: Breast-feeding and risk of epithelial ovarian cancer (clear cell/endometrioid)

Breast-feeding and risk of epithelial ovarian cancer

 Abstract

PURPOSE:

Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail.

METHODS:

Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS:

Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987).

CONCLUSIONS:

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

paywalled: Journal of Cancer Education: Knowledge of Reproductive System Cancers, Their Treatments and Side Effects (Canada)

Knowledge of Reproductive System Cancers, Their Treatments and Side Effects

 Abstract 

We explored, via an online questionnaire, knowledge of breast and reproductive system cancers in patients and non-patients who access the internet for information on these diseases. We compared that knowledge to the attention the diseases have received in medical research and on the Internet. Data were collected from 690 respondents (37 % male, 63 % female) about their knowledge of prevalence, lethality, treatments and side effects of testicular, prostate, breast, uterine, cervical and ovarian cancers. Most males, but only half of the female participants, were patients themselves. Although participants showed better knowledge of cancers specific to their own sex, both sexes felt familiar with breast cancer and less aware of other cancers. Women were as aware as men of side effects of treatments for male reproductive cancers. Sex differences in awareness appear to reflect different attitudes towards illness, bias toward females as caregivers, and the disproportionate media attention given to breast cancer.