BRCA Testing Shifts From Cancer Patients to Unaffected Women

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRCA testing in patients diagnosed with early-onset breast or ovarian cancer can identify women with high-risk mutations, which can guide treatment. Women who learn they have a high-risk mutation may also want to inform family members that they may also carry a high-risk mutation.

Additionally, BRCA testing can be used to identify high-risk mutation carriers before they develop breast or ovarian cancer. Carriers can then manage their cancer risks with screening (MRI/mammogram), chemoprevention, or prophylactic surgery. Current guidelines recommend BRCA testing for individuals who are considered high-risk for breast or ovarian cancer based on personal or family history.  However, this practice fails to identify most BRCA mutation carriers. It is estimated that more than 90% of mutation carriers have not been identified. One of the issues is that many women who do get tested are actually low-risk and do not have any personal or family history of breast or ovarian cancer.

This study assessed how BRCA testing was used in the US health care system during the past decade. We found that in 2004 most of the tests (75.7%) were performed in patients who had been diagnosed with breast or ovarian cancer. Only 24.3% of tests were performed in unaffected women. However, since 2006, the proportion of BRCA tests performed in unaffected women has increased sharply, with over 60% of the tests performed in unaffected women in 2014.

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Based on Genetic Profile, Longer Adjuvant Treatment Recommended for Some GIST Tumors

MedicalResearch.com Interview with:
Heikki Joensuu, MD

Department of Oncology
Helsinki University Hospital
University of Helsinki
Helsinki, Finland 

MedicalResearch.com: What is the background for this study?

Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear.

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Educational Disparities in Mortality Between Adults Aged 50–64 and 66–79 Years, U.S.

MedicalResearch.com Interview with:
Jiemin Ma PhD MHS
Strategic Director, Cancer Interventions Surveillance
American Cancer Society, Inc.
Atlanta, GA 30303

Jiemin Ma PhD MHS Strategic Director, Cancer Interventions Surveillance American Cancer Society, Inc. Atlanta, GA 30303

Dr. Jiemin Ma

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have shown that educational disparities are smaller in the elderly than in working-aged Americans. The differences may partly be explained by the higher health insurance coverage among the elderly (near universal coverage through Medicare for adults aged 65), as well as some aging-related changes in lifestyle and social factors (e.g. retirement). Some of the previous studies were limited by the use of proxy-reported educational information, which tended to be inaccurate for the elderly.

Our study used self-reported educational attainment to estimate relative differences in educational disparities in mortality rates between adults aged 50–64 and 66–79 years in a national representative cohort from the National Longitudinal Mortality Study (NLMS).

We found that educational disparities in all-cause mortality for ages 66–79 years were about 41% and 61% lower than those for ages 50–64 years in non-Hispanic whites and non-Hispanic blacks, respectively. Diminished disparities in the elderly were also found for deaths from cardiovascular disease and cancer among non-Hispanic Americans.

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70-Gene Signature Changes 50% of Breast Cancer Chemotherapy Advice

MedicalResearch.com Interview with:
Anne Kuijer, MD

Departments of Surgery and Radiology
University Medical Center Utrecht and
Thijs van Dalen, PhD
Department of Surgery
Netherlands Cancer Institute, Amsterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years it has become evident that clinicopathological factors fail to accurately determine prognosis in hormone receptor positive early stage breast cancer patients at intermediate risk of developing metastases. Gene-expression profiles, such as the 70-gene signature (MammaPrint) are therefore increasingly used for chemotherapy decision-making. In the current multicentre study we assessed the impact of 70-gene signature use on chemotherapy decisions in these patients. We demonstrated that, without the use of the 70-gene signature, half of patients was advised chemotherapy, which reflects the current controversy regarding chemotherapy benefit. Use of the 70-gene signature changed the chemotherapy advice in half of all patients and adherence to the 70-gene signature result was high.

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Shorter Term Precision Radiation Found Effective For Prostate Cancer

MedicalResearch.com Interview with:

Charles N Catton, MD, FRCPC Cancer Clinical Research Unit (CCRU) Princess Margaret Cancer Centre UHN

Dr. Catton

Charles N Catton, MD, FRCPC
Cancer Clinical Research Unit (CCRU)
Princess Margaret Cancer Centre
UHN 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prostate cancer is a very common malignancy which is frequently treated with external beam radiotherapy. A typical standard treatment course can extend over 7.5-8.5 weeks.

The introduction of high-precision radiotherapy treatment techniques provided the opportunity to compress treatment courses by delivering fewer, but more intensive daily treatments. The concerns with giving fewer and larger daily treatments (hypofractionation) is that toxicity may increase and that cancer control may become worse.

This international randomized trial enrolled 1206 men with intermediate risk prostate cancer and compared a standard 8 week course of external beam radiation treatment with a novel hypofractionated treatment course that was given over 4 weeks. Cancer control as measured by PSA control and clinical evidence of failure, bowel and bladder toxicity and quality of life were compared.

At a median follow-up of 6 years the hypofractionated regimen was found to be non-inferior to the standard regimen for cancer control. There was no difference early or late bladder toxicity between the two treatments. There was slightly worse early bowel toxicity during and immediately after treatment with the hypofractionated regimen, but there was actually slightly less long-term bowel toxicity with this same regimen.

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Racial Disparities in Genetic Testing of Women With Breast Cancer

MedicalResearch.com Interview with:

Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT

Dr. Cary Gross

Cary P. Gross, MD
Section of General Internal Medicine
Yale University School of Medicine
New Haven, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes.  As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments.

Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further.  That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities.

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Taking Testosterone Doesn’t Increase Prostate Cancer Risk

MedicalResearch.com Interview with:

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York

Dr. Stacy Loeb

Dr. Stacy Loeb MD Msc
Assistant Professor of Urology and Population Health
New York University Langone Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The association between exposure to testosterone replacement therapy and prostate cancer risk is controversial.  The purpose of our study was to examine this issue using national registries from Sweden, with complete records on prescription medications and prostate cancer diagnoses.  Overall, we found no association between testosterone use and overall prostate cancer risk. There was an early increase in favorable cancers which is likely due to a detection bias, but long-term users actually had a significantly reduced risk of aggressive disease.

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Clinical Outcomes Following a Low-Suspicion MRI for Prostate Cancer

MedicalResearch.com Interview with:

Lars Boesen MD PhD Department of Urology Herlev Gentofte University Hospital Herlev

Dr. Boessen

Lars Boesen MD PhD
Department of Urology
Herlev Gentofte University Hospital
Herlev

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transrectal ultrasound-guided biopsies (TRUS-bx) traditionally used for detecting prostate cancer (PCa) are prone to sampling errors due to difficulties in target identification. Therefore, concerns about the possibility of missing significant prostate cancer result in men with negative biopsy results frequently undergo repeated biopsies, leading to increased medical costs, patient anxiety and morbidity.

Multiparametric MRI (mp-MRI) has become increasingly important in prostate cancer diagnosis. A suspicious lesion can be targeted by MRI-guided biopsies and improve diagnosis. Conversely, a normal mp-MRI may non-invasively exclude the possibility of an aggressive disease, avoiding the need for further biopsies. However, there are no current guidelines for clinicians whether standard repeated biopsies (TRUS-bx) should be performed in men with either a low-suspicion mp-MRI or benign MRI-targeted biopsies of a suspicious lesion and the clinical outcome and future risk of detecting significant prostate cancer following these findings is unknown.

Therefore, we assessed the risk of being diagnosed with prostate cancer after either a low-suspicion mp-MRI or benign targeted biopsies of a suspicious lesion in men with prior negative TRUS-bx, but a persistent clinical suspicion of missed significant cancer over a follow-up period of at least three years. Our results suggest that a low-suspicion MRI in men with prior negative TRUS-bx can be used non-invasively in ruling out longer term significant cancer and immediate repeated biopsies are of limited clinical value and might be avoided even if prostate-specific-antigen levels are persistently elevated.

MedicalResearch.com: What should readers take away from your report?

Response: A low-suspicion mp-MRI in a man with prior negative TRUS-bx has a high accuracy in ruling out a significant aggressive prostate cancer during follow-up of at least three years. Thus, immediate repeated biopsies rarely find significant disease and could be avoided even if the prostate-specific-antigen level is persistently elevated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our results should be verified in larger prospective studies with a longer follow-up period to assess other clinical endpoints that include disease progression, cancer specific mortality and associated costs with an mp-MRI approach.

There are no disclosures or conflicts of interest

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
J Urol. 2017 Feb 21. pii: S0022-5347(17)30297-5. doi: 10.1016/j.juro.2017.02.073. [Epub ahead of print]
Clinical outcome following a low-suspicion multiparametric prostate MRI or benign MRI-guided biopsy to detect prostate cancer: A follow-up study in men with prior negative transrectal ultrasound-guided biopsies.
Boesen L1, Nørgaard N2, Løgager V3, Thomsen HS4.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Adiposity Related Cancer Risk May Vary On Fat Locations

MedicalResearch.com Interview with:
Arjun Gupta, MD and

Ian J. Neeland MD, Assistant Professor
Dedman Family Scholar in Clinical Care
Division of Cardiology
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Adiposity is traditionally measured using the body mass index, which refers to a persons weight in kilograms divided by their height (in meters) squared. Persons with higher body mas index have been shown to have increased risk of certain cancers, however body mass index by itself is not a completely representative measure of body fat risk, because distinct fat depots such as visceral adipose tissue, abdominal subcutaneous adipose tissue, liver fat and lower body fat have differing metabolic impact.

We aimed to study the relationship between specific fat depots and the risk of incident cancer among relatively young, multiethnic participants in the Dallas Heart Study. Individuals without prevalent cancer underwent quantification of adipose depots using MRI and DEXA scans from 2000-2002, and were followed for the development of cancer for up to 12 years. In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy and body mass index, visceral adipose tissue, subcutaneous adipose tissue or liver fat were not associated with risk of cancer but each 1-standard deviation increase in lower body fat was associated with a 31% reduced incidence of cancer.

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Drug For Diabetic Neuropathy May Also Target an Aggressive Form of Breast Cancer

MedicalResearch.com Interview with:
Chenfang Dong
Department of Pathology and Pathophysiology
Zhejiang Key Laboratory for Disease Proteomics
Zhejiang University School of Medicine
Hangzhou China 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Basal-like breast cancer (BLBC), which generally falls into the triple-negative breast cancer subtype, is associated with an aggressive clinical history, early recurrence, distant metastasis and shorter survival. The treatment of BLBC is an unmet medical need due to the absence of effective targeted therapies and poor response to standard chemotherapy. Therefore, elucidating the determinants of aggressiveness and identifying the relevant targets in BLBC are urgently needed. In this study, we report that aldo-keto reductase 1 member B1 (AKR1B1) overexpression occurs specifically in BLBC and predicts poor prognosis in breast cancer patients.

Our data reveal that AKR1B1 as a key modulator of tumor aggressiveness provides tumorigenic and metastatic advantage in basal-like breast cancer through a positive regulatory feedback loop that activates the EMT program and enhances CSC-like properties. Interestingly, epalrestat, the only AKR1B1 inhibitor that has been approved in Japan for the targeted treatment of diabetic complications, significantly inhibited cancer cell migration and invasion in vitro, suppressed tumorigenicity and metastasis of BLBC cells in mice models, displaying potent efficacy against BLBC.

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Diabetes Raises Risk of Death From Cancer in Asians

MedicalResearch.com Interview with:

Yu Chen</strong> Associate Professor, Department of Population Health Associate Professor, Department of Environmental Medicine Associate Professor, Department of Medicine NYU Langone School of Medicine

Dr. Yu Chen

Yu Chen PhD MPH
Associate Professor, Department of Population Health
Associate Professor, Department of Environmental Medicine
Associate Professor, Department of Medicine
NYU Langone School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response There is increasing evidence of an association between type 2 diabetes and cancer risk. However, previous studies in Asian only considered one or a few cancer types, included only a small number of patients with diabetes, or didn’t control for other important risk factors such as obesity.
We conducted pooled analyses of 19 prospective population-based cohorts included in the Asia Cohort Consortium (ACC), comprising data from over 771,000 individuals in the Asia.

Diabetes was associated with a 26% increased risk of death from any cancer in Asians.
Significant positive associations with diabetes were observed for the risk of death from cancers of the colorectum, liver, bile duct , gallbladder, pancreas, breast, endometrium, ovary, prostate, kidney, thyroid, as well as lymphoma. Diabetes was not statistically significantly associated with the risk of death from cancers of the bladder, cervix, esophagus, stomach, and lung or with leukemia.

MedicalResearch.com: What should readers take away from your report?

Response: Influence of diabetes on the risk of death from overall cancer, digestive cancers and breast cancer is largely similar in Asians and in developed Western countries

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: The findings indicate a potential need for appropriate cancer screening among individuals with diabetes, and a greater emphasis on lifestyle modifications to prevent diabetes and reduce cancer mortality, not only in Western populations, but also in Asians

No disclosures

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

 Chen Y, et al “Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium” Diabetologia 2017; DOI:10.1007/s00125-017-4229-z.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Colon Cancer Incidence Rises Dramatically For Young People in Their 20s and 30s

MedicalResearch.com Interview with:
Rebecca L. Siegel, MPH

Surveillance and Health Services Research
American Cancer Society
Atlanta, GA 

MedicalResearch.com: What are the main findings?

Response: It was known that colorectal cancer incidence rates are declining rapidly in people 50 years and older, but curiously increasing in people younger than 50 years. For a more comprehensive understanding of incidence patterns, we examined CRC incidence trends by 5-year age group and year of birth using age-period cohort analysis. This modeling technique helps enhance the understanding of disease trends by disentangling factors that influence all ages (period effects) from those that vary by generation (birth cohort effects).

In incidence data for almost 500,000  colorectal cancer patients during 1974-2013, we found both period and cohort effects. However, the period effects were dwarfed by the cohort effects. The age-specific risk of colorectal cancer declined during the first half of the 20thcentury, but has increased for subsequent generations since around 1950, such that those born in 1990 have twice the risk of colon cancer and 4 times the risk of rectal cancer compared to people born in 1950. Said another way, someone in their 20s today is 4 times more likely to be diagnosed with rectal cancer than someone who was in their 20s in 1970. The risk for contemporary generations has escalated back to that of people born circa 1890.

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