Targeting Breast Cancer Screening To Higher Risk Patients Reduces Overdiagnosis, Costs and Side Effects

MedicalResearch.com Interview with:

Dr Nora Pashayan PhD Clinical Reader in Applied Health Research University College London Dept of Applied Health Research London 

Dr. Pashayan

Dr Nora Pashayan PhD

Clinical Reader in Applied Health Research

University College London

Dept of Applied Health Research

London 

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

Response: Not all women have the same risk of developing breast cancer and not all women have the same potential to benefit from screening.

 

If the screening programme takes into account the individual variation in risk, then evidence from different studies indicate that this could improve the efficiency of the screening programme. However, questions remain on what is the best risk-stratified screening strategy, does risk-stratified screening add value for money, and what are benefit and harm trade-offs.

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Higher Vitamin D Levels Linked to Lower Breast Cancer Incidence

MedicalResearch.com Interview with:

Cedric F. Garland, Dr.P.H., F.A.C.E. Adjunct Professor Division of Epidemiology Department of Family Medicine and Public Health University of California San Diego La Jolla, California 92093-0620

Dr. Garland

Cedric F. Garland, Dr.P.H., F.A.C.E.
Adjunct Professor
Division of Epidemiology
Department of Family Medicine and Public Health
University of California San Diego
La Jolla, California 92093-0620

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

Response: Studies mapping death rates from female breast cancer in the US, the former USSR and Canada by Drs. Edward Gorham, and Frank and Cedric Garland revealed for the first time in history that death rates from breast cancer tracked latitude where people lived.

The rates were highest in the least sunny northern tier of states, lowest in the sunny southwest. This led these scientists to be the first to theorize that vitamin D prevents breast cancer” said study first author Sharon McDonnell. Continue reading

Panitumumab (Vectibix) For Primary HER2-Negative Inflammatory Breast Cancer

MedicalResearch.com Interview with:

Naoto Tada Ueno, M.D., Ph.D., F.A.C.P. Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXNaoto Tada Ueno, M.D., Ph.D., F.A.C.P.
Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

 

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

Response: The best outcome of inflammatory breast cancer (IBC) is dependent on achieving a pathological completed response after neoadjuvant chemotherapy for primary inflammatory breast cancer, which is the most aggressive type of breast cancer.

We have conducted extensive preclinical work, which showed that EGFR is a potential therapeutic targets of IBC.

Based on this preclinical data, we have conducted a phase II study to determine the pathological complete response rate of panitumumab plus neoadjuvant chemotherapy for HER2 negative primary inflammatory breast cancer.  Continue reading

First in Class Antibody-Drug Conjugate Shows Promise in Metastatic Breast Cancer

MedicalResearch.com Interview with:

Dr. Aditya Bardia  MD, MPH Assistant Professor, Medicine, Harvard Medical School Attending Physician, Medical Oncology Massachusetts General Hospital

Dr. Bardia

Dr. Aditya Bardia  MD, MPH
Assistant Professor, Medicine
Harvard Medical School
Attending Physician, Medical Oncology
Massachusetts General Hospital

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

Response: Hormone receptor-positive (HR+)/ and human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common sub-type of breast cancer. While metastatic HR+/HER2- breast cancer is initially treated with endocrine therapy-based combinations, including CDK 4/6 inhibitors, patients eventually have disease progression, but the response rate to standard chemotherapy is low (~10-15 percent, post-taxane setting). In particular, patients with visceral disease have a poor prognosis.

In this trial, we evaluated the efficacy of sacituzumab govitecan in patients with metastatic HR+/HER2- breast cancer, who had measurable disease and had received prior therapies for metastatic breast cancer. We observed an overall response rate of 31 percent in a heavily pre-treated population (prior number of therapies for metastatic breast cancer = 5; number of patients with prior CDK 4/6 inhibitor use = 69 percent). The responses were durable (median duration of response = 7.4 months). Neutropenia was the main adverse event noted (grade 3 neutropenia = 42 percent), and two patients (3.7 percent) discontinued the clinical trial due to adverse events. The response rate in patients with visceral metastaseswas 27 percent.  Continue reading

Novel SM-88 Therapy Has Potential Efficacy in Metastatic Breast Cancer

MedicalResearch.com Interview with:

Dr. Giuseppe Del Priore, MD, MPH Chief Medical Officer of Tyme Inc. 

Dr. Del Priore

Dr. Giuseppe Del Priore, MD, MPH
Chief Medical Officer of Tyme Inc.

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

Response: Metastatic breast cancer, sometimes also called “stage IV” or “advanced breast cancer,” is the most extensive stage of breast cancer. It is an invasive cancer that has spread to other parts of the body, most often bones, lungs, liver, and brain. The current standard of care for metastatic breast cancer is systemic drug therapies, such as hormone therapy, chemotherapy, targeted drugs or a combination of these.  Because they reach every cell in the body, they have side effects that can worsen the patient’s quality of life. Existing treatments cannot cure metastatic breast cancer and are palliative in intent. This presents a great unmet need and challenge in treating patients with metastatic breast cancer.

SM-88 is a novel relatively non-toxic combination therapy that harnesses cancer’s unique cell metabolism and oxidative stress to selectively drive cancer cell death. Earlier studies with SM-88 therapy demonstrated its potential efficacy in breast and other metastatic cancers. In this current report, we assessed the efficacy of SM-88 in patients with metastatic breast cancer from the first in human “Phase 1” and compassionate use programs from 2012 to 2017. Data demonstrated the potential efficacy of SM-88 in metastatic breast cancer with favorable safety and quality of life profiles. In addition, there were no indications of cross-resistance based on hormone profile, previous treatments or metastatic site. This is an extremely important finding since most cancer deaths are due to resistance to subsequent therapies.  As predicted by the SM-88 mechanism of action, we could not detect this problem with SM-88 use.

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Everolimus Plus Exemestane vs Monotherapy for ER+ HER2- Advanced Breast Cancer

MedicalResearch.com Interview with:

Guy Jerusalem, MD, PhD CHU Sart Tilman Liege and Liege University Liege, Belgium

Dr. Jerusalem

Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium

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

Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.

The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).

A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design.  Continue reading

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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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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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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Greater Risk of Breast Cancer in Women With Schizophrenia

MedicalResearch.com Interview with:
Chuanjun Zhuo, MD, PhD

Department of Psychiatric Laboratory
Department of Psychiatric Neuroimaging Faculty
Tianjin Mental Health Center
Tianjin, China 

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

Response: According to previous epidemiological studies, women with schizophrenia may be associated with significantly increased risk of breast cancer. However, the results of these studies were not always consistent. In view of the fact that medical care for patients with schizophrenia is becoming multidisciplinary, we aimed to evaluate the risk of breast cancer in women with schizophrenia via a meta-analysis of relevant cohort studies. We included twelve cohorts and adopted the recently proposed prediction interval to evaluate the heterogeneity among the included studies.

We found that schizophrenia was associated with about 30% increased risk of breast cancer incidence in women. However, significant heterogeneity existed of the included studies, which indicates that more extensive researches into the potential mechanisms underlying the associations between schizophrenia and breast cancer risk are needed.

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Genetic Variant of p53 Associated With Poor Breast Cancer Survival

MedicalResearch.com Interview with:
Maureen E. Murphy, Ph.D.
Program Leader and Professor
Molecular and Cellular Oncogenesis and
Subhasree Basu PhD
Postdoctoral researcher
The Wistar Institute
Philadelphia, PA 19104

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

Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis.

In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  Continue reading

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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