Some Breast Cancer Patients With Complete Response To Neoadjuvant Therapy Can Avoid Further Surgery

MedicalResearch.com Interview with:

Audree Tadros, MD, MPH Chief Administrative Fellow, Breast Surgical Oncology Training Program Department of Breast Surgical Oncology MD Anderson Cancer Center and

Dr. Tadros

Audree Tadros, MD, MPH
Chief Administrative Fellow, Breast Surgical Oncology Training Program
Department of Breast Surgical Oncology
MD Anderson Cancer Center and

Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Cancer Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program

Dr. Kuerer

Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Cancer Research
Dept of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program

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

Response: Neoadjuvant chemotherapy (NCT) has the ability to confer a pCR (pathologic complete response-when no residual cancer is found) in both the breast and axillary lymph nodes. We know that this is most likely to occur in women with HER2 positive and triple negative disease. The high rate of pCR among these patients raises the question of whether surgery is still required, particularly among those who will receive adjuvant radiation therapy.

Until recently, we lacked the ability to pre-operatively predict patients who achieved a breast pCR. Recently, we completed a clinical feasibility trial examining the ability of image-guided biopsy to predict a pCR after neoadjuvant chemotherapy. Our biopsy technique was able to accurately predict a pCR in 98% of patients with only a 5% false negative rate. Based upon these findings, we believe we can accurately determine which patients achieve a breast pCR. This led us to develop a clinical trial to see if breast surgery is redundant in patients who achieve a pCR. An important question that remained was if we are going to omit breast surgery in these exceptional responders, can we also omit axillary surgery?

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Bisphosphonates Can Be Reduced In Second Year of Breast Cancer Metastases

MedicalResearch.com Interview with:

Gabriel N. Hortobagyi, MD, FACP, FASCO Professor, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX 77230-1439

Dr. Gabriel Hortobagyi

Gabriel N. Hortobagyi, MD, FACP, FASCO
Professor, Department of Breast Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX 77230-1439 

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

Response: Bisphosphonates have been commercially available for several decades as supportive care for patients with bone metastases. They reduce the frequency and severity of bone-related complications. While the optimal dose and short-term scheduling of zoledronic acid (and previously, pamidronate) have been determined, there has been no research to determine how long these drugs need to be maintained nor the optimal dose and schedule beyond the first year of therapy. These questions are particularly important for this family of drugs, since they are incorporated into bone and not excreted from the body for many years.

We set out to determine whether a reduction in the frequency of administration of zoledronic acid (every 12 weeks) was able to maintain the therapeutic efficacy of this intervention when compared to the “standard” schedule of administration (every 4 weeks). It was a prospective, randomized, non-inferiority trial that recruited patients with metastatic breast cancer with bone metastases and who had previously received 9 or more doses of zoledronic acid or pamidronate. The primary endpoint was the proportion of patients with one or more skeletal-related events. Four hundred and sixteen patients were randomized in a 1:1 ratio. The two groups were comparable at baseline. After the first year of follow-up, there was no statistically significant difference in SRE rate between the two arms, confirming the non-inferiority fo the every-12-week schedule of zoledronic acid.

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Image-Guided Biopsies May Reduce Need For Surgery in Breast Cancer Patients Who Respond to Chemotherapy

MedicalResearch.com Interview with:

Henry M. Kuerer, MD, PhD, FACS</strong> Executive Director, Breast Network Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program

Dr. Henry M. Kuerer

Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Network Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Research
Department of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program

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

Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation.

We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed?

The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not.

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One Size Fits All Strategy No Longer Works For Treatment of Ovarian Cancer

MedicalResearch.com Interview with:

Larissa A. Meyer, MD MPH F.A.C.O.G. Assistant Professor Dept of Gynecologic Oncology and Reproductive Medicine Houston, TX 77030-1362

Dr. Larissa Meyer

Larissa A. Meyer, MD MPH F.A.C.O.G.
Assistant Professor
Dept of Gynecologic Oncology and Reproductive Medicine
Houston, TX 77030-1362

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

Response: Despite the completion of two randomized controlled trials, controversy regarding the optimal approach for the treatment of advanced ovarian cancer remains. Our observational study highlights the importance of thoughtful selection of individuals for primary cytoreductive surgery for advanced ovarian cancer. Our results suggest that primary cytoreductive surgery may improve survival for patients with stage IIIC ovarian cancer who are likely to achieve an optimal cytoreduction, while neoadjuvant chemotherapy may be the preferred option for many women with stage IV ovarian cancer.

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Molecular Subtyping of Rectal Cancers Can Guide Prognosis, Treatment and Future Screening

MedicalResearch.com Interview with:

Y. Nancy You, MD, MHSc Associate Professor Section of Colorectal Surgery Department of Surgical Oncology Medical Director Familial High-risk Gastrointestinal Cancer Clinic University of Texas MD Anderson Cancer Center

Dr. Y. Nancy You

Y. Nancy You, MD, MHSc
Associate Professor
Section of Colorectal Surgery
Department of Surgical Oncology
Medical Director
Familial High-risk Gastrointestinal Cancer Clinic
University of Texas MD Anderson Cancer Center

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

Response: Despite the progress in the treatment of many cancers, colorectal cancer (CRC) remains the third most common and lethal cancer in the US. Over 130,000 people are expected to be diagnosed and over 50,000 patients will die from CRC this year. In the recent years, the most exciting development has been our understanding of the molecular complexity of CRC.

Currently, four major molecular subtypes of colorectal cancer are recognized. Our study focuses on the Consensus Molecular Subtype 1, which accounts for up to 15% of CRCs, and is characterized by a deficiency in DNA mismatch repair (dMMR), a high level of mutations (i.e. hypermutated), by instability in parts of the genome called microsatellites, and by strong immune activation. Prior to our study, patients with rectal cancer that belong to this molecular subtype have represented an unknown, in terms of their prognosis, and how the tumors respond to current treatments. More importantly, this molecular subtype harbor a genetic condition that can be transmitted within the family called “Lynch Syndrome”. So we designed our study to fill these gaps in our understanding that exist in this subtype of CRCs and to highlight key clinical care issues related to the caring for patients with a genetic syndrome.

The main findings are that rectal cancers belonging to this molecular subtype have favorable prognosis, respond well to standard chemoradiation, and are linked to Lynch Syndrome and should be treated at centers with expertise in hereditary cancer syndromes. Continue reading

Genetic Signatures Reveal Gender Differences In Cancer Biomarkers

MedicalResearch.com Interview with:

Dr. Han Liang PhD Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Faculty Member, Baylor College of Medicine Houston, TX

Dr. Han Liang

Dr. Han Liang PhD
Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology
The University of Texas MD Anderson Cancer Center
Faculty Member, Baylor College of Medicine
Houston, TX

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

Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages.

We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups.

One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures.

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Gene Therapy to Spinal Cord Offers Potential Hope to Peripheral Nerve Pain Patients

MedicalResearch.com Interview with:

Hui-Lin Pan, MD, PhD Helen T. Hawkins Distinguished Professor  and Deputy Division Head for Research Division of Anesthesiology and Critical Care, Unit 110 The University of Texas MD Anderson Cancer Center Houston, TX

Dr. Hui-Lin Pan

Hui-Lin Pan, MD, PhD
Helen T. Hawkins Distinguished Professor
and Deputy Division Head for Research
Division of Anesthesiology and Critical Care, Unit 110
The University of Texas MD Anderson Cancer Center
Houston, TX

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

Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain.

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Study Targets Obesity Genes That May Raise Risk of Kidney Cancer

MedicalResearch.com Interview with:

Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas

Dr. Xifeng Wu

Dr. Xifeng Wu, MD PhD
Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences
Director, Center for Translational and Public Health Genomics
Professor, Department of Epidemiology
Division of Cancer Prevention and Population Sciences
The University of Texas MD Anderson Cancer Center, Houston, Texas

Medical Research: What is the background for this study? What are the main findings?

Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms.

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Immunotherapy Drug Nivolumab May Help Some Aggressive HPV-Induced Anal Cancers

MedicalResearch.com Interview with:

Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center

Dr. Van Morris

Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center

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

Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.

Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.

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Hepatitis C Raises Risk of HPV Head and Neck Cancers

MedicalResearch.com Interview with:

Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030

Dr. Harrys Torres

Harrys A. Torres, MD, FACP, FIDSA
Associate Professor
Director of Hepatitis C Clinic
Department of Infectious Diseases, Infection Control and Employee Health
The University of Texas MD Anderson Cancer Center
Houston TX 77030

Medical Research: What is the background for this study? What are the main findings?

Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers.

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High Glycemic Index May Raise Lung Cancer Risk Especially in Never Smokers

MedicalResearch.com Interview with:

Xifeng Wu, M.D., Ph.D Professor of Epidemiology

Dr. Xifeng Wu

Xifeng Wu, M.D., Ph.D
Professor of Epidemiology and

Dr. Stephanie Claire Melkonian PhD Epidemiologist, Postdoctoral Research Fellow

Dr. Melkonian

Dr. Stephanie Claire Melkonian  PhD
Epidemiologist, Postdoctoral Research Fellow
The University of Texas MD Anderson Cancer Center

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

Response: Glycemic index (GI) assigns foods an indexed value to show how quickly and how much carbohydrates in the food cause blood glucose levels to rise after eating and is a measure of overall carbohydrate quality. Glycemic load (GL) is a related measure that is calculated by multiplying Glycemic index by the amount of carbohydrates in grams in that specific food and by the amount consume, then dividing by 100. Previous studies have investigated the association of GI and GL with certain types of cancer, including colorectal, stomach, and pancreatic cancer, but there has been limited research into the association with lung cancer.

We conducted a study using patients and control subjects from an ongoing case-control study of lung cancer conducted at MD Anderson. The patients were newly diagnosed and had not received treatment other than surgery. The healthy control subjects were selected from patient lists at Kelsey-Seybold Clinics, a large physician group in the Houston area. The study results encompass 1,905 cases and 2,413 controls. Using data collected from in-person interviews regarding health histories and dietary behaviors, we were able to categorize the study subjects according to their dietary Glycemic index and GL.

What we found was that individuals in the highest category of GI were at an almost 50% increased risk for developing lung cancer as compared to those in the lowest group. This association was different based on different subtypes of cancer. Most interestingly, however, among those individuals that never smoked, high Glycemic index was associated with an almost 2 fold increased risk of lung cancer. In other words, we found a more profound association between GI and lung cancer in never smokers in this study.

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Gene Expression Profile Can Indicate Aggressive Prostate Cancer

MedicalResearch.com Interview with

Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA

Dr. Dingxiao Zhang

Dr. Dingxiao Zhang Ph.D
Department of Epigenetics and Molecular Carcinogenesis
University of Texas MD Anderson Cancer Center
Smithville, TX 78957, USA

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

Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing.

One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers.

Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

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