Mammograms Reduce Mortality From Higher Grade Breast Cancers

MedicalResearch.com Interview with:

Prof-Stephen-Duffy.jpg

Prof. Duffy

Stephen W. Duffy
Professor of Cancer Screening
Wolfson Institute of Preventive Medicine,
Barts and The London School of Medicine and Dentistry
Queen Mary University of London

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

Response: The phenomenon of length bias, whereby screening has more chance of detecting slow growing tumours, has been known about for some years. This has led some colleagues to speculate that breast cancer screening only benefits those with slow-growing, less aggressive cancers, and does not reduce deaths from more aggressive, rapidly progressing cancers.

In this study, we addressed this question directly using data from a randomised trial of mammographic screening. We calculated the reduction in mortality from grade 1 (less aggressive), grade 2 (intermediate) and grade 3 (most aggressive) cancers, as a result of screening. We found that the greatest reduction in breast cancer mortality was from the aggressive, fast-growing grade 3 cancers, contrary to what had been suspected.  Continue reading

BRCA1/BRCA2 Testing Varies Widely Worldwide

MedicalResearch.com Interview with:

Amanda Toland, PhD, Cancer biology and genetics researcher of The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute 

Dr. Toland

Amanda Toland, PhD,
Cancer biology and genetics researcher of
The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

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

Response: The Breast Information Core (or BIC) is a database that catalogs BRCA1 and BRCA2 sequenced variants.  The BIC is hosted by the National Human Genome Research Institute at NIH and has a steering committee that oversees the BIC and has members from Europe, the middle East, Australia and the US.  In BIC SC discussions, we learned that there are differences in how BRCA1/2 clinical is testing between countries.

To characterize this variation, we performed an international survey of 86 genetic testing labs from around the world.

Our main findings are that there were many variations between testing laboratories.  These include: technologies differed for finding “large” genetic sequence variants, what parts of the genes were assessed, how genetic variants were classified as disease associated or not being associated with diseases, if genetic sequencing information was shared in public databases and testing volume.

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With or Without Reconstruction, Hard To Predict How You Will Feel After Mastectomy

MedicalResearch.com Interview with:
Dr. Clara Nan-hi Lee, MD Comprehensive Cancer Center The Ohio State UniversityDr. Clara Nan-hi Lee, MD
Comprehensive Cancer Center
The Ohio State University 

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

Response: The decision about breast reconstruction is very challenging because it’s unfamiliar, involves complex risk information, affects very personal concerns, and happens at a stressful time. One of the challenges is to predict how one will feel after the surgery. We know from psychology research that people often mis-predict their future emotions. So we were interested to see how well women predict their future well being after surgery.

The main findings are that patients having mastectomy without reconstruction believed they would be less satisfied than they turned out to be. And patients having mastectomy with reconstruction believed they would be more satisfied than they turned out to be. Continue reading

Improving Adjuvant Clinical Trials By Including Only Patients For Whom Current Therapies Do Not Work Well

MedicalResearch.com Interview with:

Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director of Breast Cancer Translational Research Co-Director of the Yale Cancer Center Genetics, Genomics and Epigenetics Program Yale School of Medicine New Haven, CT  06511

Dr. Pusztai

Lajos Pusztai, M.D, D.Phil.
Professor of Medicine
Director of Breast Cancer Translational Research
Co-Director of the Yale Cancer Center Genetics, Genomics and Epigenetics Program
Yale School of Medicine
New Haven, CT  06511

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

Response: Overall, about 85% of newly diagnosed stage I-III breast cancer patients will not die of their disease, and this roughly equates to an 85% cure rate. Of course cure rates are higher for stage I cancers and lower for stage III cancers. An 85% overall cure rate is good but not good enough, we continuously try to develop new therapies hoping to push these rates to 90%…,95%…etc. However, it is not possible to cure a patient twice over. For example, if surgery plus endocrine therapy cures all patients, the addition of chemotherapy cannot improve on it no matter how effective it is. If surgery plus endocrine therapy cures 95%, adding the perfect chemo to this treatment can only bring about a 5% improvement, and very good chemo that would push cure from 95% to 97%, would require a very large trial including many thousands of patients.

This is an increasingly common scenario in modern breast cancer adjuvant trials (where the goal is to improve survival and cure); the control arm that receives the current standard of care invariably does better than expected and the experimental arm only improves outcome by 1-3% that does not reach statistical significance.  The painful conclusion from these trials is that we do not know if the new drug actually works or not because there were not enough events to demonstrate an effect.

Of course, a lot of patients in the study were also exposed to a new drug with all of its associated toxicities who could not possibly benefit from it.

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Relative Risk of Breast-Anaplastic Large Cell Lymphoma With Implants is Low But Still Elevated

MedicalResearch.com Interview with:

Dr. Mintsje de Boer, MD Resident plastic surgery
Department of Plastic, Reconstructive and Hand-Surgery
Maastricht University Medical Centre+, Maastricht the Netherland

On behalf of the Netherlands BIA-ALCL Consortium: Daphne de Jong (Hematopathologist, VU university medical Center, Amsterdam, the Netherlands), Hinne Rakhorst (Plastic Surgeon, MST/ZGT, Enschede, the Netherlands) René van der Hulst (Plastic surgeon, MUMC+ Maastricht, the Netherlands) Flora van Leeuwen (Epidemiologist, Netherlands Cancer Institute, Amsterdam, the Netherlands), Jan Paul de Boer (Hemato-oncologist, Netherlands Cancer Institute, Amsterdam, the Netherlands) Lucy Overbeek (Database expert PALGA, Houten, the Netherlands), 

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

Response: Breast implants are one of the most commonly used medical devices worldwide. Associations with breast cancer, connective tissue diseases and auto-immune diseases have never been unequivocally supported. For lymphoma risk, this is different and several reports have suggested an association between breast implants and risk of anaplastic large cell lymphoma in the breast (breast-ALCL).

Over the past few years, the number of women with breast implants reported with breast-ALCL has strongly increased. This has resulted in significant attention amongst medical professionals and women alike with publications in medical journals and lay press. In part due to the rarity of the disease and due to the lack of breast implant prevalence data in the population, the absolute risks of breast-ALCL are largely unknown, precluding evidence-based counseling about implants. In the Netherlands, we are in the unique position to be able to retrieve all diagnosed breastALCL since 1990 as well as appropriate population-based control groups from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). This has allowed a formal epidemiological risk assessment study based on sufficient numbers. Moreover, using combined and complementary sources of information, we have been able to determine age- and calendar year-specific implant prevalence rates to determine reliable absolute risks.

This study could be successfully performed thanks to a multidisciplinary taskforce consisting of plastic surgeons, hematopathologists, epidemiologists, hemato-oncologists and radiologists from the several large institutions in the Netherlands  Continue reading

Deep Learning Algorithms Can Detect Spread of Breast Cancer To Lymph Nodes As Well or Better Than Pathologists

MedicalResearch.com Interview with:
Babak Ehteshami Bejnordi Department of Radiology and Nuclear Medicine Radboud University medical center, NijmegenBabak Ehteshami Bejnordi

Department of Radiology and Nuclear Medicine
Radboud University medical center, Nijmegen

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

Response: Artificial intelligence (AI) will play a crucial role in health care. Advances in a family of AI popularly known as deep learning have ignited a new wave of algorithms and tools that read medical images for diagnosis. Analysis of digital pathology images is an important application of deep learning but requires evaluation for diagnostic performance.

Accurate breast cancer staging is an essential task performed by the pathologists worldwide to inform clinical management. Assessing the extent of cancer spread by histopathological analysis of sentinel lymph nodes (SLN) is an important part of breast cancer staging. Traditionally, pathologists endure time and labor-intensive processes to assess tissues by reviewing thousands to millions of cells under a microscope. Using computer algorithms to analyze digital pathology images could potentially improve the accuracy and efficiency of pathologists.

In our study, we evaluated the performance of deep learning algorithms at detecting metastases in lymph nodes of patients with breast cancer and compared it to pathologist’s diagnoses in a diagnostic setting.

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Breast Cancer Survival Remains Lower For Black Women

MedicalResearch.com Interview with:
“Family Weekend 2014-Breast Cancer Walk” by Nazareth College is licensed under CC BY 2.0
Dr. Jacqueline Miller, MD
Division of Cancer Prevention and Control
CDC 

MedicalResearch.com: What efforts have proven successful in reducing racial disparities like these?

Response: While some racial disparities will exist due to differences in tumor types, improving early diagnosis and providing specific treatment based on tumor characteristics in a timely fashion would result in reducing breast cancer disparities.

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About 20% Increased Risk of Breast Cancer in Women On Oral Contraceptives

MedicalResearch.com Interview with:
“Birth control pills” by lookcatalog is licensed under CC BY 2.0Lina Mørch PhD, MSc

Senior Researcher
Rigshospitalet

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

Response: There was a lack of evidence on contemporary hormonal contraception and risk of breast cancer. In particular the knowledge of risk with newer progestins was sparse.

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PTK6 Inhibitors May Target Endocrine Therapy-Resistant ER+ Breast Cancer

MedicalResearch.com Interview with:

Hanna Irie MD PhD Assistant Professor Oncology Mount Sinai Health System 

Dr. Irie

Hanna Irie MD PhD, senior author
Assistant Professor of Medicine
(Hematology and Medical Oncology) and Oncological Sciences at The Tisch Cancer Institute,
Icahn School of Medicine at Mount Sinai

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

Response: Our study identified PTK6 as a critical gene regulating survival of ER+ breast cancer cells.

PTK6 inhibition also suppresses growth and survival of ER+ breast cancer cells that are resistant to the effects of therapies commonly used to treat patient ER+ breast cancers, making PTK6 an attractive candidate therapeutic target for these resistant cancers.

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Should Hormonal Therapy Be Extended Past Five Years After Estrogen+ Breast Cancer?

MedicalResearch.com Interview with:

Dr Hongchao Pan PhD Medical Research Council Population Health Research Unit Clinical Trial Service Unit & Epidemiological Studies Unit Nuffield Department of Population Health Oxford 

Dr Hongchao Pan

Dr Hongchao Pan PhD
Medical Research Council Population Health Research Unit
Clinical Trial Service Unit & Epidemiological Studies Unit
Nuffield Department of Population Health
Oxford

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

Response: We’ve known for a long time that recurrences can occur late in women with oestrogen receptor positive breast cancers. Our study aimed to assess how big the risk was for women who had taken endocrine treatment (tamoxifen or an aromatase inhibitor) for 5 years, which greatly reduces the risk of recurrence (by about a half during treatment and one third for the 5 years after stopping). We also wanted to find out what factors influenced the risk of recurrence, and whether some women had such a low risk that they could safely stop hormonal treatment after 5 years or, conversely, whether other women had a particularly high risk so it would make sense for them to keep on taking hormonal treatment.

What we found by following the progress of over 60,000 women who had stopped hormonal treatment at 5 years is that the risk of the cancer spreading stays about the same for the next 15 years. This risk is much higher for women whose breast cancer had spread to the nodes when first diagnosed but even for those with the best outlook (no spread to the lymph nodes and small tumours), there was a 10% chance of cancer spread over 15 years.

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Study Finds No Increased Recurrence Risk in Breast Cancer Survivors Who Become Pregnant

MedicalResearch.com Interview with:

Hatem A. Azim Jr, MD, PhD Adjunct Assistant Professor, American University of Beirut (AUB) Beirut, Lebanon 

Dr. Azim

Hatem A. Azim Jr, MD, PhD
Adjunct Assistant Professor, American University of Beirut (AUB)
Beirut, Lebanon 

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

Response: This study aimed at evaluating the safety of pregnancy after breast cancer particularly in patient with history of ER+ breast cancer; a subset in which safety of future pregnancy is always put into question by oncologists and obstetricians.

This study included more than 300 pregnant women and 800 non-pregnant breast cancer patients who acted as a comparator group The results show that after more than 7 years after pregnancy, women who became pregnant did not have an increased risk of recurrence compared to those who did not become pregnant irrespective of ER status. There was no impact of breastfeeding, abortion or time of pregnancy on patient outcome.

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Recurrent Metastatic Breast Cancer Remains a Clinical Challenge With Poor Prognosis

MedicalResearch.com Interview with:

Judith A. Malmgren, PhD President, HealthStat Consulting, Inc Epidemiology Department University of Washingto

Dr. Malmgren

Judith A. Malmgren, PhD
President, HealthStat Consulting, Inc
Epidemiology Department
University of Washington

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

Response: Metastatic breast cancer (MBC) has two types, de novo stage IV MBC discovered to be metastatic at initial diagnosis as advanced disease and recurrent MBC found on follow up after diagnosis and treatment for initial invasive breast cancer. Our institutional breast cancer registry tracks both de novo metastatic breast cancer and invasive breast cancer for distant metastases. With this information we were able to compare the presentation, treatment and outcomes of both types, something that is not possible in national SEER data as recurrent MBC is not tracked.

We found a remarkable improvement in 5-year survival from 28% to 55% over time among the de novo metastatic breast cancer patients.  Recurrent MBC 5-year survival did not improve in the same time period (23% to 13%) although incidence of recurrent MBC fell from 18% to 7% from 1990 to 2010. Incidence of recurrent metastatic breast cancer hormone receptor and HER2 positive breast cancer declined the most, leaving a large number of triple-negative recurrent metastatic breast cancer cases in the most recent time period.

Worse metastatic breast cancer survival was associated with recurrent vs. de novo MBC, hormone receptor negative disease, older age (70+) and visceral dominant disease. HER2 positive disease was associated with better outcomes.

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Machine Learning Applied To Predicting High-Risk Breast Lesions May Reduce Unnecessary Surgeries

MedicalResearch.com Interview with:

Manisha Bahl, MD, MPH Director, Breast Imaging Fellowship Program, Massachusetts General Hospital Assistant Professor of Radiology, Harvard Medical School

Dr. Bahl

Manisha Bahl, MD, MPH
Director, Breast Imaging Fellowship Program,
Massachusetts General Hospital
Assistant Professor of Radiology,
Harvard Medical School

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

Response: Image-guided biopsies that we perform based on suspicious findings on mammography can yield one of three pathology results: cancer, high-risk, or benign. Most high-risk breast lesions are noncancerous, but surgical excision is typically recommended because some high-risk lesions can be upgraded to cancer at surgery. Currently, there are no imaging or other features that reliably allow us to distinguish between high-risk lesions that warrant surgery from those that can be safely followed, which has led to unnecessary surgery of high-risk lesions that are not associated with cancer.

We decided to apply machine learning algorithms to help us with this challenging clinical scenario: to distinguish between high-risk lesions that warrant surgery from those that can be safely followed. Machine learning allows us to incorporate the full spectrum of diverse and complex data that we have available, such as patient risk factors and imaging features, in order to predict which high-risk lesions are likely to be upgraded to cancer and, ultimately, to help our patients make more informed decisions about surgery versus surveillance.

We developed the machine learning model with almost 700 high-risk lesions, then tested it with more than 300 high-risk lesions. Instead of surgical excision of all high-risk lesions, if those categorized with the model to be at low risk for upgrade were surveilled and the remainder were excised, then 97.4% malignancies would have been diagnosed at surgery, and 30.6% of surgeries of benign lesions could have been avoided.

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Most Women Unaware of Breast Cancer Overdiagnosis and Overtreatment

MedicalResearch.com Interview with:

Rebekah Nagler PhD Assistant professor Hubbard School of Journalism and Mass Communication University of Minnesota

Dr. Nagler

Rebekah Nagler PhD Assistant professor
Hubbard School of Journalism and Mass Communication
University of Minnesota 

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

Response: Both the American Cancer Society (ACS) and the U.S. Preventive Services Task Force (USPSTF) have stated that women in their 40s–or, in the case of ACS, women ages 40-44–should have the choice to decide when they want to start screening for breast cancer. These organizations recommend that women in this age group weigh the benefits and risks of mammography screening, with the goal of making an informed decision about when to start screening. Yet recent research has shown that women are more aware of the benefits of mammography screening than the harms, including overdiagnosis and overtreatment (doi:10.1001/jamainternmed.2017.2247). We therefore wondered whether women actually have the information they need to make informed screening decisions.

In a population-based sample of 429 U.S. women ages 35-55, we found that awareness of breast cancer overdiagnosis (16.5%) and overtreatment (18.0%) was low. Moreover, we found that most women did not find statements about these harms to be believable and persuasive.

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Kisqali (ribociclib) Plus Aromatase Inhibitor Receives EU Approval For Advanced Breast Cancer

MedicalResearch.com Interview with:

Wolfgang Janni, MD, PhD University of Ulm MONALEESA-2 investigator

Dr. Janni

Wolfgang Janni, MD, PhD
University of Ulm
MONALEESA-2 investigator

MedicalResearch.com: What is the background for the MONALEESA-2 trial? What are the main findings?

Response: The Phase III MONALEESA-2 trial was the primary study that supported the recent European approval of Kisqali (ribociclib). Findings from the study showed superior efficacy and demonstrated safety of Kisqali plus letrozole compared to letrozole alone in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer who received no prior therapy for their advanced breast cancer.

The trial showed Kisqali plus letrozole reduced the risk of progression or death by 43% versus letrozole alone. At a pre-planned analysis, Kisqali plus letrozole demonstrated a median progression-free survival (PFS) of 25.3 months compared to 16.0 months for letrozole alone (HR=0.568 (95% CI: 0.457-0.704; p<0.0001)). More than half of patients (55%) with measurable disease taking Kisqali plus letrozole experienced a tumor reduction of at least 30%. Finally, Kisqali plus letrozole demonstrated rapid clinical improvement in patients with measurable disease, with 76% seeing a reduction in tumor size after only eight weeks versus 67% with letrozole alone.

Most side effects in the MONALEESA-2 trial were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and/or reduction. The most common grade 3/4 adverse events (reported at a frequency ≥5%) for Kisqali plus letrozole compared to letrozole alone were neutropenia (60% vs 1%, respectively), leukopenia (21% vs 1%), hypertension (10% vs. 11%), increased alanine aminotransferase level (9% vs. 1%), lymphopenia (7% vs. 1%) and increased aspartate aminotransferase level (6% vs. 1%).

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