Improved Detection of Microsatellite Instability in Early Colorectal Lesions

open access

 Abstract
Microsatellite instability (MSI) occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR) tracts. Adenomas from 160 patients, ranging in age from 29–55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega). This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers........

Results

Study population and samples

Patients with a history of cancer were preferentially selected for this study resulting in 32.5% (52/160) of cases having a personal or family history of one or more 1^st or 2^nd degree relatives with colon or other LS-associated cancers. Most were colon cancers (43/52). The other LS-associated cancers were ovarian, uterine and gastric..... 

Discussion

.....MSI testing of polyps has been proposed for the early detection of LS, but is currently not a realistic, cost-effective approach due to low sensitivity in early pre-cancerous lesions. The goal of this study was to investigate whether the use of new LMR markers can increase detection of MSI in adenomas to a level approaching that reported for colorectal carcinomas with current marker systems (i.e., >90% sensitivity) [23]. The use of the LMR panel did significantly increase the sensitivity (100% for this study population) for detection of mismatch repair deficient lesions over currently available marker panels without significantly decreasing specificity. Studies to determine the sensitivity for detection of LS still need to be performed to determine if the higher levels of MSI achieved using the new LMR markers will transform MSI testing into a practical screening tool for pre-cancerous lesions and early detection of LS.

Challenges and Opportunities in Measuring Cancer Recurrence in the United States

Abstract

 Cancer recurrence and disease-free survival are key outcomes for measuring the burden of illness, assessing the quality of cancer care, and informing decisions about increasingly costly cancer therapies. Yet information about recurrence is not collected in cancer registries or other population-based data sources. To address the lack of population-based recurrence information, researchers are increasingly using algorithms applied to health claims to infer recurrence. However, the validity of these approaches has not been comprehensively evaluated. In this commentary, we review existing studies and discuss options for improving the availability of recurrence data. We found that the validity of claims-based approaches appears promising in small, single institution studies, but larger population-based studies have identified substantial limitations with using claims to identify recurrence. With the increasing availability of health data, there are potential options that can be implemented to enhance information about recurrence. These options include design of software for the electronic medical record that enables rapid and standardized reporting of recurrence, use of electronic pathology reports to facilitate streamlined collection of recurrence by cancer registries, and mandates by insurers to require reporting of recurrence on health claims submitted by physicians. All of these options will require that governmental agencies, health insurers, professional societies, and other groups recognize the importance of population-based recurrence data and determine that this information is a priority for assessing cancer outcomes and costs.

 Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Patient-funded trials may do more harm than good, ethicists warn (crowdfunding)

science news

Hereditary Cancer-Associated Mutations in Women Diagnosed with Two Primary Cancers: An Opportunity to Identify Hereditary Cancer Syndromes after the 1st Cancer Diagnosis

Myriad Genetics - open access - full text

 Abstract

Objectives: Patients with hereditary cancer syndromes are at high risk for a second primary cancer. Early identification of these patients after an initial cancer diagnosis is the key to implementing cancer risk-reducing strategies.  

Methods: A commercial laboratory database was searched for women with a history of both breast and ovarian or colorectal and endometrial cancer who underwent genetic testing for hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS).  

Results: Among women with both breast and ovarian cancer, 22.4% (2,237/9,982) had a BRCA1 or BRCA2 mutation. Among women with both colorectal and ovarian cancer, 28.1% (264/941) had a mutation associated with LS. In 66.6% of BRCA1 or BRCA2 mutation carriers and in 58.3% of LS mutation carriers, >5 years passed between the cancer diagnoses. Of patients with HBOC and LS, 56 and 65.2%, respectively, met the National Comprehensive Cancer Network guidelines for hereditary cancer testing after their initial diagnosis based on their personal cancer history alone.  

Conclusions: A substantial number of women tested for LS or HBOC after being diagnosed with two successive primary cancers were diagnosed with a hereditary cancer syndrome. In many cases, the time interval between the diagnoses was long enough to allow for the implementation of surveillance and/or prophylactic measures.

".... Many of the women in the present analysis were diagnosed with breast cancer after the age of 45 but they may still have qualified for testing based on family history or triple negative status. It is especially important to survey women with HBOC after a breast cancer diagnosis because many of them will survive their breast cancer but remain at risk for ovarian cancer, which has a higher mortality rate......Furthermore, it reinforces the role of gynecologists and gynecologic oncologists in supporting genetic testing for patients with endometrial cancer, as nearly half of all patients with LS present first with a gynecologic cancer.....Of note, a 5-year remission is a common oncology mark after which a patient is considered cancer-free. The data presented here suggest that patients with hereditary cancer syndromes are still vulnerable to a second diagnosis after the 5-year mark.....


 

Patients can teach doctors these 5 things

 teach

Here are 5 things doctors learn from their patients all the time:


1. People are brave and have a remarkable capacity for resilience. Patients courageously put up with terrible illnesses and refuse to give up in the face of adversity....

Invited Commentary Ovarian cancer of tubal origin, incessant ovulation and implications for clinical practice

pdf open access

Am J Clin Exp Obstet Gynecol 2015;2(3):130-135 www.ajceog.us /ISSN:2330-1899/AJCEOG0010914

Invited Commentary Ovarian cancer of tubal origin, incessant ovulation and implications for clinical practice
Mahmoud F Fathalla Department of Obstetrics and Gynecology, Assiut University, Egypt Received May 31, 2015; Accepted June 4, 2015; Epub July 10, 2015; Published July 15, 2015

JCO Podcast by Dr Deborah Armstrong: Intraperitoneal Therapy for Ovarian Cancer: No More Excuses

JCO Podcast
  
Copyright © 2015 by the American Society of Clinical Oncology

Users can play the podcast directly in the audio player embedded below. If Flash is disabled on your browser, you can save the file directly to your computer or open on your mobile device by clicking on "Play/download file."

Intraperitoneal Therapy for Ovarian Cancer: No More Excuses
By Deborah K. Armstrong


(Play/download file - duration 08:46, file size 8 MB)

Association between tumor infiltrating immune cells, circulating tumor cells in blood and disseminated tumor cells in the bone marrow in patients with primary ovarian cancer

Abstract 369: AACR

Background: We recently showed that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood of primary ovarian cancer patients significantly correlated with reduced progression free survival (PFS) and overall survival (OS). On the one hand, this negative prognostic impact might be related to different factors like chemotherapy resistant and stem cell like cells. On the other hand, the microenvironment of the primary tumor might influence tumor cell spread and thus, outcome of the disease. Here we analyzed whether infiltrating leukocytes in the tumor (TILs) and/or stroma (SILs) are associated with DTCs before and after therapy as well as with CTCs before therapy in patients with primary ovarian cancer.

Patients and Methods: DTCs before (n = 145) and after therapy (n = 57) were studied using immunocytochemistry applying the pan cytokeratin (CK) antibody A45-B/B3. 2 × 5 ml bloods of 111 patients were analyzed for CTCs with the AdnaTest OvarianCancer (AdnaGen AG, Langenhagen, Germany) for the detection of EpCAM, MUC-1, CA-125 and beta-Actin transcripts. Tissue microarrays of all patients were stamped from paraffin embedded specimens........

Results: Before therapy, DTCs were detected in 51/145 patients (35%) and after therapy in 24/57 patients (42%). CTCs were detected in 24/111 patients (22%) before therapy. In general, the highest infiltration of lymphocytes was found in the stroma. Whereas high numbers of CD8 were detected in the stroma and the tumor, high numbers of CD4 and CD68 infiltrates were mainly found in the stroma. The expression of CD4 (SIL) and CD8 (SIL) was significantly associated with the presence of CTCs (p = 0.04) whereas CD4 (SIL) significantly correlated with DTCs before (p = 0.03) and CD8 (SIL) with DTCs after therapy (p = 0.04). No association was found between DTCs/CTCs and the expression of CD68.

Conclusion: Here we demonstrate significant associations between infiltrating lymphocytes and the presence of DTCs and CTCs. Ongoing studies are now including the expression of CD20 and CD45 and final statistical analysis, including immune signatures, all clinical parameters, PFS and OS, will give deeper insights in the interaction of tumor infiltrating immune cells and tumor cell dissemination.

Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer

abstract

AIMS:

Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α) has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-β is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-β expression in solid tumors. Additional or simultaneous expression of FR-β could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-β is evaluated in ovarian, breast and colorectal cancer.

METHODS:

FR-β expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis.

RESULTS:

FR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-β expression in macrophages. FR-β status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-β expression (p=0.022).

CONCLUSIONS:

FR-β expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-β is not regarded as a suitable target in colorectal cancer.

Review of Commonly Used Serum Tumor Markers and Their Relevance for Image Interpretation

abstract

Serum tumor markers are firmly entrenched as one of the primary tools in an oncologist's armamentarium. They can be implemented in a broad range of applications from diagnostic assistance, assessing prognosis, or guiding therapeutic decisions. However, tumor markers also have limitations, which significantly impact how they should be used. Radiologists should be familiar with the following most prevalent tumor markers, which will all be discussed here: prostate-specific antigen (prostate), carcinoembryonic antigen (colon), α-fetoprotein (hepatocellular and testicular), carbohydrate antigen 19.9 (pancreas), cancer antigen 125 (ovarian), human chorionic gonadotropin/lactic dehydrogenase (testicular), and chromogranin A (neuroendocrine). This knowledge should avoid needless intervention, enhance image interpretation, and ultimately provide optimal patient care.

Deleterious BRCA1/2 mutations in an urban population of Black women - U.S.

abstract

Information on the prevalence of deleterious BRCA1 and BRCA2 (BRCA1/2) mutations in clinic-based populations of Black women is limited. In order to address this gap, we performed a retrospective study to determine the prevalence of deleterious BRCA1/2 mutations, predictors of having a mutation, and acceptance of risk-reducing surgeries in Black women. In an urban unselected clinic-based population, we evaluated 211 self-identified Black women who underwent genetic counseling for hereditary breast-ovarian cancer syndrome. BRCA1/2 mutations were identified in 13.4 % of the participants who received genetic testing. Younger age at diagnosis, higher BRCAPRO score, significant family history, and diagnosis of triple-negative breast cancer were associated with identification of a BRCA1/2 mutation. Of the affected patients found to have a deleterious mutation, almost half underwent prophylactic measures. In our study population, 1 in 7 Black women who underwent genetic testing harbored a deleterious BRCA1/2 mutation independent of age at diagnosis or family history.

Perspective in infertility: the ovarian stem cells

open access

What is the Difference Between Palliative Care and Hospice?

 Insight
  

Dana-Farber August 23, 2013

New Study Reveals Ovarian Cancer Survival Rates and Best Treatments – article

 AARP article

Cytoreductive Surgery and HIPEC 1st Relapse of Ovarian Cancer

 Blogger's Note: a morbidity rates explanation (~31%) would require full text (paid subscription)

abstract

 Background: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC).

Patients and Methods: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival.

Results: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%.

Conclusion: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates.

Pfizer, Bristol revive cancer drugs that rev up immune system - media

 Reuters

(new journal) End Life Journal

July 2015, Volume 5, Number 1

 

Why Is Getting a Patient on a Clinical Trial So Difficult

 ASCO Connection

Pan-Cancer Genetic Testing Provides Important Info for Identifying/Treating At-Risk Populations (re: NCCN)

Targeted Oncology

....Pan-cancer multigene panels include genes that are expressed across a variety of cancer types, and offer the possibility of identifying potentially deleterious genes in patients who might not otherwise be tested.3,4 For example, an individual with a family history of breast cancer (who would qualify for genetic testing for BRCA1/BRCA2 mutation) might also have a mutation in one or more of the LS genes, which would generally not be evaluated......(eg. NCCN guidelines)

 FIGURE. Examples of LS-mutation–positive patients who do not meet NCCN LS testing criteria.3

FIGURE. Examples of LS-mutation–positive patients who do not meet NCCN LS testing criteria.3 - See more at: http://www.targetedonc.com/publications/targeted-therapy-news/2015/may-2015/pan-cancer-genetic-testing-provides-important-information-for-identifying-and-treating-at-risk-populations#sthash.AmxIpdif.dpuf

Pan-cancer multigene panels include genes that are expressed across a variety of cancer types, and offer the possibility of identifying potentially deleterious genes in patients who might not otherwise be tested.^3,4 For example, an individual with a family history of breast cancer (who would qualify for genetic testing for BRCA1/BRCA2 mutation) might also have a mutation in one or more of the LS genes, which would generally not be evaluated.  - See more at: http://www.targetedonc.com/publications/targeted-therapy-news/2015/may-2015/pan-cancer-genetic-testing-provides-important-information-for-identifying-and-treating-at-risk-populations#sthash.AmxIpdif.dpuf

Are Spicy Foods a Recipe for Longevity? (short video analysis)

Medpage Today

LAPAROSCOPIC SURGERY FOR EARLY OVARIAN CANCER (Russia)

abstract

For the period from 2003 to 2014 at the Oncogynecology Department laparoscopic surgery for ovarian cancer was performed in 49 patients aged 19 to 76 years. During the surgical interventions special attention was paid to the principles of oncological radicalism and ablastics, the volume of surgery depended on the extent of tumor process, morphological characteristics of tumor, a patient's age and the desire to preserve reproductive function. In 42 (85.7%) cases laparoscopic procedures were conducted to restaging (after non-radical operations in gynecological hospitals). In all 49 patients a histological form of ovarian tumor corresponded to adenocarcinoma. Mean operative time was 140 ± 10,5 minutes, the average blood loss--80,2 ± 14,3 ml. Postoperative complications (bleeding from the omentum) were recorded in 1 (2%) patient, the need for conversion was occurred in 4 (8.2%) cases due to the adhesive process or signs of dissemination. As a result of laparoscopic surgery an increase in staging of disease was fixed in 14 cases (28.6%). Follow-up median was 45 months, relapses occurred in 5 (10.2%) patients. Of 49 patients 2 (4.1%) died from disease progression. Disease-free and overall survival rates were 89.8% and 95.9%, respectively. Thus, data of world literature and our own experience indicate the potential equivalent of laparoscopic and laparotomy approaches in treatment for early ovarian cancer.

The prognostic significance of anti-angiogenesis therapy in ovarian cancer: a meta-analysis

 Full text 

(abstract) Objective

The prognostic value of anti-angiogenesis therapy in ovarian cancer patients is currently under debate. In this study, we assessed the effects of anti-angiogenesis therapy on the progression free survival (PFS) and overall survival (OS) of ovarian cancer patients.

Discussion

Angiogenesis has been implicated in the pathogenesis and progression of ovarian cancer potentially due to the promotion of tumor growth, ascites, and metastases [5]. Therefore, therapies based on angiogenesis-specific pathway are being extensively studied in ovarian cancer [6], [7]. Our present meta-analysis was based on a pool of 8 phase III and 4 phase II clinical trials and thus differed from the two existing meta-analyses, which included only clinical trials involving bevacizumab [20], [21].

Comparison of Colorectal and Endometrial Carcinoma in Patients with Lynch-Like Syndrome versus Patients with Lynch Syndrome

Blogger's Note: of interest to those with dual malignancies/mutation negative genetic testing...

abstract

 Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinoma identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathologic features of colorectal and endometrial carcinoma in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified

Are clear cell carcinomas of the ovary and endometrium phenotypically identical? A proteomic analysis

Abstract

 Summary

Phenotypic differences between otherwise similar tumors arising from different gynecologic locations may be highly significant in understanding the underlying driver molecular events at each site and may potentially offer insights into differential responses to treatment. In this study, the authors sought to identify and quantify phenotypic differences between ovarian clear cell carcinoma (OCCC) and endometrial clear cell carcinoma (ECCC) using a proteomic approach. Tissue microarrays were constructed from tumor samples of 108 patients (54 ECCCs and 54 OCCCs). Formalin-fixed samples on microarray slides were analyzed by matrix-assisted laser desorption/ionization mass spectrometry, and 730 spectral peaks were generated from the combined data set. A linear mixed-effect model with random intercept was used to generate 93 (12.7%) peaks that were significantly different between OCCCs and ECCCs at the fold cutoffs of 1.5 and 0.667 and an adjusted P value cutoff of 1.0 × 10⁻¹⁰. Liquid chromatography–tandem mass spectrometry was performed on selected cores from each group, and peptides identified therefrom were compared with lists of statistically significant peaks from the aforementioned linear mixed-effects model to find matches within 0.2 Da. A total of 53 candidate proteins were thus identified as being differentially expressed in OCCCs and ECCCs, 45 (85%) of which were expressed at higher levels in ECCCs than OCCCs. These proteins were functionally diverse and did not highlight a clearly dominant cellular theme or molecular pathway. Although ECCCs and OCCCs are very similar, some phenotypic differences are demonstrable. Additional studies of these differentially expressed proteins may ultimately clarify the significance of these differences.

Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer (California)

Blogger's Note: this abstract provides nothing new to what is already known except possibly public perception

abstract

OBJECTIVE:

To identify characteristics associated with long-term survival for patients with epithelial ovarian cancer using the California Cancer Registry.

METHODS:

A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow-up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared with three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years.

RESULTS:

A total of 3,582 out of 11,541 (31%, confidence interval 30.2-31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and nonserous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer.

CONCLUSION:

Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced-stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling.

Petition · Protest High Cancer Drug Prices so all Patients with Cancer have Access to Affordable Drugs

Petition - change.org

 9,944 needed to reach 35,000

 Protest High Cancer Drug Prices so all Patients with Cancer have Access to Affordable Drugs to Save their Lives

Background - Cure

 Speak Out About Rising Cancer Drug Prices, Group of Oncology Experts Urges
 
Oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs.

BY TONY HAGEN
PUBLISHED TUESDAY, AUGUST 4, 2015

If you’re a patient with cancer or an advocate for that community and you have thoughts on the rising costs of treatment, it’s time to make your voice heard. That’s the opinion of 118 well-known cancer experts who have come together to spotlight the issue.
In a July 23 commentary published in the journal Mayo Clinic Proceedings, the oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs. The petition can be found on Change.org at http://chn.ge/1DCWT1M.
“A cancer patient–based grassroots movement that advocates against the high price of cancer drugs can accomplish a great deal,” wrote the experts in the commentary, which outlines their recommended drug pricing reforms.
The authors suggest that advocates model their efforts on the movement by HIV/AIDS activists in the late 1980s and 1990s, which helped to spur faster drug development and broaden access to promising experimental drugs.......

Speak Out About Rising Cancer Drug Prices, Group of Oncology Experts Urges

Oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs.

BY TONY HAGEN

PUBLISHED TUESDAY, AUGUST 4, 2015

Discussions >>

Talk about this article with other patients, caregivers, and advocates in the General Discussions CURE discussion group.

If you’re a patient with cancer or an advocate for that community and you have thoughts on the rising costs of treatment, it’s time to make your voice heard. That’s the opinion of 118 well-known cancer experts who have come together to spotlight the issue.

In a July 23 commentary published in the journal Mayo Clinic Proceedings, the oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs. The petition can be found on Change.org at http://chn.ge/1DCWT1M.

“A cancer patient–based grassroots movement that advocates against the high price of cancer drugs can accomplish a great deal,” wrote the experts in the commentary, which outlines their recommended drug pricing reforms.

The authors suggest that advocates model their efforts on the movement by HIV/AIDS activists in the late 1980s and 1990s, which helped to spur faster drug development and broaden access to promising experimental drugs.

- See more at: http://www.curetoday.com/articles/speak-out-about-rising-cancer-drug-prices-group-of-oncology-experts-urges?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%5Femail%5F8%2D5%2D15#sthash.3LZfPSad.dpuf

Speak Out About Rising Cancer Drug Prices, Group of Oncology Experts Urges

Oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs.

BY TONY HAGEN

PUBLISHED TUESDAY, AUGUST 4, 2015

Discussions >>

Talk about this article with other patients, caregivers, and advocates in the General Discussions CURE discussion group.

If you’re a patient with cancer or an advocate for that community and you have thoughts on the rising costs of treatment, it’s time to make your voice heard. That’s the opinion of 118 well-known cancer experts who have come together to spotlight the issue.

In a July 23 commentary published in the journal Mayo Clinic Proceedings, the oncology experts supported a patient-driven online petition asking Congress to give the government, patients and other stakeholders more power when it comes to negotiating prices for cancer drugs. The petition can be found on Change.org at http://chn.ge/1DCWT1M.

“A cancer patient–based grassroots movement that advocates against the high price of cancer drugs can accomplish a great deal,” wrote the experts in the commentary, which outlines their recommended drug pricing reforms.

The authors suggest that advocates model their efforts on the movement by HIV/AIDS activists in the late 1980s and 1990s, which helped to spur faster drug development and broaden access to promising experimental drugs.

- See more at: http://www.curetoday.com/articles/speak-out-about-rising-cancer-drug-prices-group-of-oncology-experts-urges?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%5Femail%5F8%2D5%2D15#sthash.3LZfPSad.dpuf

Mutation spectrum and risk of colorectal cancer in African American families with Lynch Syndrome

abstract
 

Background & Aims

African Americans (AAs) have the highest incidence and mortality of colorectal cancer (CRC) in the United States (US). Few data are available on genetic and non-genetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC syndrome, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch Syndrome.

Methods

We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk studying members of the mutation-carrying families.

Results

We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at an age of 80 y were estimated to be 36.2% (95% confidence interval [CI], 10.5%–83.9%) for men and 29.7% (95% CI, 8.31%–76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44–56.5).

Conclusions

We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1—some were found in multiple individuals and some have not been previously reported. Differences in the mutation spectrum are likely to reflect the genetic diversity of this population.

Earlier Detection of Ovarian Cancer (CA125/p53)

video (1:46 min)

 Posted on : 05/13/15
Added : 3 months ago

Description: Dr. Bast discusses a study that may help in early detection of ovarian cancer by detecting a patient’s own immune response to tumor-associated antigens.

Robert C. Bast, Jr., MD, vice president, Translational Research, The University of Texas MD Anderson Cancer Center,

Advances in the Management of Advanced and Relapsed Ovarian Cancer (immunotherapy)

video

 © 2015 Imedex, LLC. Shared By : imedex
Posted on : 07/24/15
Added : 12 days ago

Description: Filmed on location in Las Vegas during the 21st Annual NOCR Meeting, this webcast is part of a series that provides expert discussions from physicians and researchers from around the USA reviewing current standards of management and analyzing the most important new data that has the potential to modify treatment guidelines.

In this presentation, Dr. Bradley J. Monk discusses the latest advances in the management of advanced and relapsed ovarian cancer.
 

Ovarian cancer in BRCA1/2 mutation carriers: The impact of mutation position and family history on the cancer risk

abstract
 

Highlights

•

The impact of mutation position and family history on ovarian cancer (OC) risks was assessed.

•

In BRCA1 families women with a mutation within the OCCR region have higher OC risks.

•

In BRCA2 families, mutation position did not significantly affect the OC risk.

•

In BRCA2 families, a family history including only OC presented a strong impact on OC risk.

Treatment of climacteric symptoms in survivors of gynaecological cancer

abstract

 Highlights

•

Physicians are reluctant in prescribing HRT in gynaecological cancer survivors because of the fear that hormones may influence the risk of recurrence.

•

No evidence of increased risk in the available studies on HRT in survivors of endometrial, ovarian and squamous cervical cancer, even if no definitive results have been formulated

•

The positive effect of HRT on the quality of life seems to outweigh the unfounded suspicion about an increased risk of recurrence

•

It is mandatory to inform patients about alternative therapies other than estrogens, in particular for prevention of osteoporosis and cardiovascular disease.

---

Different treatments (surgery, radiotherapy, chemotherapy) for gynaecological cancers may cause ovarian failure or increase menopausal symptoms. There is a widespread reluctance among physicians to prescribe hormone replacement therapy (HRT) to the survivors of gynaecological cancer. This review analyses the use of HRT and of alternative therapies in such women. Squamous cervical cancer is not estrogen dependent and thus HRT is not contraindicated. While a cautious approach to hormone-dependent cancer is warranted, for women treated for non-hormone-related tumours alternative treatments for menopausal symptoms should be given due consideration, as any reluctance to prescribe HRT for them has neither a biological nor a clinical basis. In studies of HRT for survivors of endometrial and ovarian cancer, for instance, no evidence of increased risk was found, although no definitive conclusions can yet be formulated. The positive effect of HRT on quality of life seems to outweigh the unfounded suspicion of an increased risk of recurrence of non-hormone-related tumours. Effective non-hormonal alternatives for vasomotor symptoms are selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors.

Low-grade epithelial ovarian cancer: a number of distinct clinical entities?.

abstract

Purpose of review: The purpose of this study is to summarize the contemporary understanding of low-grade epithelial ovarian cancers.

Recent findings: Low-grade serous ovarian cancer is biologically distinct from high-grade serous ovarian cancer. It is associated with a high incidence of K-RAS and B-RAF mutations. Although described as indolent due to median progression-free and overall survivals of 20 and 99 months, respectively, with a median age of diagnosis of 43 years, it accounts for a significant number of patient-years lost. Retrospective studies suggest response rates of 5% for chemotherapy and 9% for antioestrogen therapy. A prospective study of the mitogen-activated protein kinase kinase inhibitor selumetinib (response rate 15%) and retrospective bevacizumab studies suggest that these may be more effective approaches.

Limited retrospective clinical data and even more sparse molecular data suggest that similar distinctions may exist between low-grade endometrioid and mucinous ovarian cancers and their respective high-grade counterparts, but more research is required in order to clarify the biological differences and the implications that these have for management.

Summary: The results of phase III mitogen-activated protein kinase kinase inhibitor studies in low-grade serous ovarian cancer and further clinical and biological assessment of low-grade endometrioid and mucinous ovarian cancers are urgently required.