Can a Pill Plus Infrared Light Replace Mammograms?

MedicalResearch.com Interview with:

Greg Thurber, PhD Assistant Professor Department of Chemical Engineering Assistant Professor Department of Biomedical Engineering University of Michigan 

Dr. Thurber

Greg Thurber, PhD
Assistant Professor
Department of Chemical Engineering
Assistant Professor
Department of Biomedical Engineering
University of Michigan 

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

Response: Most current disease screening strategies rely on either blood tests, where the physician can obtain information on specific disease molecules but has no idea where they originated in the body, or anatomical imaging, where the physician can see changes in the structure of tissues but doesn’t have any molecular information. We wanted to develop a method that could provide both molecular information and an image of where these molecules were located. We know from decades of research in cancer that this is a molecular disease, so providing molecular information to the physician will help improve detection and diagnosis. Breast cancer screening provides an excellent opportunity to apply this approach to improve detection. Currently, estimates indicate that we are overspending $4 billion per year on the overdiagnosis and overtreatment of breast cancer because we cannot accurately determine which patients need treatment and which can be safely monitored with no intervention. Despite this problem with overdiagnosis, however, screening saves lives…we simply need a better way.

Molecular imaging has the capability of providing both molecular information and the location within the body. However, most of these techniques are expensive and use ionizing radiation, meaning there is a small risk of actually causing cancer. This is not acceptable for screening large numbers of otherwise healthy patients. To avoid this risk and provide a safe, inexpensive, and relatively easy method for patients to undergo screening, we decided to develop near-infrared fluorescent imaging agents that can be taken as a pill. The goal is for the patient to simply take a pill a day or two before their visit, and then the physician shines near-infrared light on the breast tissue to detect tumors where they ‘light up’ by giving off a different color of light.

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Benefits and Complexities of More Breast Cancer Genes to Screen For

Dr-Allison W. Kurian

Dr. Kurian

MedicalResearch.com Interview with:
Allison W. Kurian, M.D., M.Sc.

Associate Professor of Medicine (Oncology) and of Health Research and Policy
Director, Women’s Clinical Cancer Genetics Program
Stanford University School of Medicine
Stanford, CA 94305-5405 

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

Response: Changes in genetic sequencing technology and regulation have allowed much cheaper testing of many more genes in recent years. We investigated how these changes have affected hereditary cancer risk evaluation in women newly diagnosed with breast cancer.

The main findings are that more comprehensive multiple-gene sequencing tests have rapidly replaced more limited tests of two genes (BRCA1 and BRCA2) only. This has helped patients by doubling the chance of finding an important gene mutation that can change their treatment options.

However, there are important gaps in how this new, more comprehensive sequencing is used: more testing delays and more uncertain results, particularly among racial/ethnic minority women.  Continue reading

Osteoporosis Drug Has Potential To Fight Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Chenfang Dong, Ph.D & M.D.
Professor
Department of Pathology and Pathophysiology
Zhejiang University School of Medicine, 

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 a poor clinical outcome due to few treatment options and poor therapeutic response; thus there is a pressing need to elucidate the determinants of aggressiveness in BLBC and identify potential therapeutic targets for this challenging disease.

By analyzing gene expression profiles of breast cancer in multiple publicly available datasets that contain over 5000 cases, we have identified that UDP-galactose ceramide galactosyltransferase (UGT8), a key enzyme in the sulfatide biosynthetic pathway, promotes BLBC progression by activating sulfatide-αVβ5 axis.

Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which has the potential to become a valuable targeted drug for treating Basal-like breast cancer.  Continue reading

Liquid Biopsy Can Guide Radiation Therapy in Early Stage Breast Cancer

MedicalResearch.com Interview with:

Chelain Goodman, MD PhD PGY-3, Radiation Oncology Northwestern University Chicago, IL 60611

Dr. Goodman

Chelain Goodman, MD PhD
PGY-3, Radiation Oncology
Northwestern University
Chicago, IL 60611

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

Response: Circulating tumor cells are cancer cells that are shed from the primary tumor into the peripheral blood stream and are hypothesized to be one of the first steps in the initiation of metastatic progression. Prospective studies have demonstrated that approximately 15-25% of patients with early-stage breast cancer can be found to have at least one circulating tumor cell in a small sample of their blood. Currently, all patients with early-stage invasive breast cancer who undergo breast conserving surgery receive adjuvant radiation therapy. In these analyses, we wanted to determine whether presence of circulating tumor cells may be predictive of benefit of radiation therapy following surgery.

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What’s the Prognosis If You Get Breast Cancer After a Negative Mammogram?

MedicalResearch.com Interview with:

Anne Marie McCarthy, PhD Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston

Dr. McCarthy

Anne Marie McCarthy, PhD
Department of Medicine
Massachusetts General Hospital and Harvard Medical School
Boston

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

Response: Mammography is effective in reducing breast cancer mortality. However, it is not perfect, and approximately 15% of breast cancers are diagnosed despite a negative mammogram before the next recommended screening.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Using data from the NCI funded PROSPR (Population-Based Research Optimizing Screening through Personalized Regimens) Consortium, we determined the rates of cancer diagnosis within one year following a negative or positive screening mammogram. The rate of cancer diagnosis within one year of a negative mammogram was small (5.9 per 10,000 screenings), but those cancers were more likely to have poor prognosis than cancers diagnosed after a positive mammogram (43.8% vs. 26.9%). As expected, women with dense breasts were more likely to have cancer diagnosed within 1 year of a negative mammogram. However, breast density was not a good predictor of poor prognosis among women diagnosed with cancer after a negative mammogram. Younger women were more likely to be diagnosed with poor prognosis breast cancer after a negative screening mammogram.

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Which Cancers Cost The Most To Treat?

MedicalResearch.com Interview with:

Matthew P. Banegas, PhD, MPH Center for Health Research Kaiser Permanente

Dr. Banegas

Matthew P. Banegas, PhD, MPH
Center for Health Research
Kaiser Permanente

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

Response: Despite a large body of research on cancer care costs, we observed a significant evidence gap. Namely, while about one-half of cancer diagnoses in the U.S. occur among people under age 65, it can be difficult to find good data on the costs of care for this population. That’s because most of the current literature on cancer care costs is based on SEER Medicare data, which are limited to Medicare fee-for-service beneficiaries.

At a time of rising costs and an ever-increasing number of new therapies, we felt it was important to improve our understanding of cancer costs for U.S. adults of all ages. We examined medical care costs for the four most common types of cancer in the United States: breast, colorectal, lung, and prostate cancer.

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Protein Associated with Metastatic Breast Cancer

MedicalResearch.com Interview with:
Yingfei Wang, Ph.D. and Weibo Luo, Ph.D.
Department of Pathology
UT Southwestern Medical Center
Dallas TX 75390

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

Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer.

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Digital Breast Tomosynthesis + Synthetic 2D Mammography Detects More Breast Cancers

MedicalResearch.com Interview with:
Dr. Solveig Hofvind, Dr. Philos.
Cancer Registry of Norway
Majorstuen, Oslo

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

Response: To test out Digital Breast Tomosynthesis (DBT) in combination with synthethic images (SM) as a screening tool for breast cancer.

We screened the women in Oslo with DBT+SM using equipment from Hologic, while women in the neighboring counties were screened with Digital Mammography.

MedicalResearch.com: What are the main findings? 

Response: We found a 50% higher rate of screen-detected breast cancer among women screened with DBT+SM compared with  Digital Mammography

Both the rate of invasive breast cancer and ductal carcinoma in situ was higher. Tumors detected with DBT+SM were smaller and less aggressive compared to those detected with Digital Mammography.
.
We found no differences in recall rates between the two groups.

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

Response: Screening with Digital Breast Tomosynthesis and Synthetic 2D Mammography detects more breast cancer as Digital Mammography. 

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

Response: We need to follow the women for interval breast cancer, but also the rate of screen-detected breast cancer and the characteristics of the tumors in the next screening round. 

MedicalResearch.com: Is there anything else you would like to add?

Response: The pro and cons of implementing Digital Breast Tomosynthesis and Synthetic 2D Mammography in a screening setting need further investigation, according to cost-effectiveness, also in a financial perspective. 

Citations: 

Radiology. 2018 Mar 1:171361. doi: 10.1148/radiol.2018171361. [Epub ahead of print]

Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Digital Mammography: Evaluation in a Population-based Screening Program.

Hofvind S1, Hovda T1, Holen ÅS1, Lee CI1, Albertsen J1, Bjørndal H1, Brandal SHB1, Gullien R1, Lømo J1, Park D1, Romundstad L1, Suhrke P1, Vigeland E1, Skaane P1. 

 

 

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Everolimus plus Endocrine Therapy: Effective 1st Line Option for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer

MedicalResearch.com Interview with:

Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque

Dr. Royce

Melanie E. RoyceMDPhD
Division of Hematology/Oncology
University of New Mexico Comprehensive Cancer Center
Albuquerque

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

Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.

A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%).

Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression.
Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5).

Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.  Continue reading

Obesity Fuels Resistance To Anti-VEGF Therapy in Breast Cancer Patients

MedicalResearch.com Interview with:

Dr. Fukumura

Dr. Fukumura

Dai Fukumura, M.D., Ph.D
Associate Professor, Radiation Oncology
Harvard Medical School
Deputy Director, Edwin L. Steele Laboratory,
Radiation Oncology, Massachusetts General Hospital
Boston, MA 

 

 

Joao Incio

Dr. Incio

Dr. Joao Incio PhD
Post-Doc, Edwin L. Steele Laboratory

 

 

 

 

 

Dr. Rakesh K. Jain PhD

Dr. Jain

Dr. Rakesh K. Jain PhD
Andrew Werk Cook Professor of Tumor Biology and director of the Edwin L. Steele Laboratories for Tumor Biology
Rradiation oncology department
Massachusetts General Hospital and Harvard Medical School.

 

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

Response: Based on promising data from preclinical studies and subsequent increase in progression-free survival in patients, anti-vascular endothelial growth factor (VEGF) therapy received accelerated approval for metastatic breast cancer. However, this approval was withdrawn in the United States based on the lack of overall survival benefit in several subsequent phase III studies in metastatic and adjuvant settings. Potential mechanisms of resistance to anti-VEGF therapy include the upregulation of alternative angiogenic and pro-inflammatory factors. Production of some of these factors has been shown to increase in obesity specifically in hypoxic adipose tissues including the breast. Given that up to 70% of breast cancer (BC) patients in the United States are overweight or obese, we addressed one simple but important question in this study: Is obesity contributing to anti-VEGF treatment resistance in breast cancer?

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