University of Pennsylvania Health System

Focus on Cancer

Tuesday, September 27, 2011

Understanding the Biology of Breast Cancer

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the second of four posts about the latest findings in treating breast cancer. 

One of the larger trends in cancer treatment, especially breast cancer treatment, is the increasing ability to identify biologic subtypes of the disease and the need for better prognostic biomarkers, or biomarkers that provide information regarding outcome without regard for therapy.

Angela DeMichele, MD, MSCE
At the 2011 ASCO conference, Angela DiMichele, MD, MSCE, assistant professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, talked about the important role biology plays in identifying these markers. As co-program leader of the Abramson Cancer Center's National Cancer Institute (NCI)-approved breast cancer program, she discussed one such marker, Ki-67, and intrinsic genetic subtypes.

Two studies (Abstracts 500 and 501) provide support for the validity of Ki-67 as a means of identifying highly proliferative tumors and those that are more likely to respond to specific chemotherapy regimens. Ki-67 is a cancer antigen that is found in growing, dividing cells but is absent in the resting phase of cell growth. This characteristic makes Ki-67 a good tumor marker. This test is done on a sample of tumor tissue, to help predict your prognosis.

Many studies have been done to determine Ki-67's value as a tumor marker test. Researchers agree that high levels of Ki-67 indicate an aggressive tumor and predict a poor prognosis and tumors that tested positive with high levels of Ki-67, have a higher risk of recurrence.

Perhaps more intriguing is the emergence of intrinsic subtypes of breast cancer. Gene expression studies have identified several distinct breast cancer subtypes. The value of this information is less clear, but understanding the specific biologic characteristics that influence these subtypes may help determine which patients will respond to which therapies.

Cancer researchers now understand that breast cancer is a spectrum of diseases, ranging from those that are more endocrine driven to those that are more chemosensitive. These findings reinforce the need for accurate molecular profiling for all breast cancer patients.

OncotypeDX has become a standard means for molecular profiling and guiding breast cancer treatment decisions, but another, potentially even more comprehensive tool is on the horizon. PAM-50 screens for 50 genes and is potentially more sensitive, but is not yet clinically available. Further studies are needed to validate its use.

Abstracts can be found on the 2011 ASCO meeting website.

Learn more about breast cancer treatment at Penn’s Abramson Cancer Center.

Are you at risk for breast cancer? Attend Penn Women’s Cancer Conference – Focus on Your Risk of Breast/Ovarian Cancer

Are you a breast cancer survivor? Attend the Penn Women’s Cancer Conference – Life after Breast Cancer

Coming up next, How Weight and Hormones Affect Breast Cancer Outcomes.

Monday, September 19, 2011

Latest Trends in Treating Breast Cancer - 2011

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the first of four posts about the latest findings in treating breast cancer.

The summary of the latest news in breast cancer treatment was delivered in rapid-fire style at the Abramson Cancer Center’s 2011 Update in Breast Cancer ASCO summary course. Unfortunately, many of those attending the annual conference thought the news was "not as exciting as last year," because of the lack of any single, major breakthrough.

At the 2010 conference, Penn cancer researchers highlighted the promising results of targeted immunotherapy in treating metastatic breast cancer.

While there may have been no single big story, significant data were presented across the full platform of breast cancer-related topics: from prevention to neoadjuvant therapy and managing metastatic disease. Major emphasis was placed on improved understanding of the biology of breast cancer and the development of more targeted therapies tailored to match the specific genetic profiles of patients.

From the Headlines: FDA Approval for Bevacizumab
David M. Mintzer, MD
One issue that has been in the headlines during the past months is the status of FDA approval of bevacizumab (Avastin®) for first-line of treatment of HER2-negative metastatic breast cancer in combination with paclitaxel.  Bevacuzumab received fast track approval in 2008. Subsequent studies, including those presented at ASCO 2011, demonstrated modest improvements in progression-free survival, but none in overall survival or improvement in disease-related symptoms.  The down sides of the drug are its toxicity and high costs of administration.

Just hours after the update concluded, the Oncologic Drugs Advisory Committee voted 6-0 to withdraw FDA approval for bevacizumab for treating HER2-negative metastatic breast cancer. While the committee vote was unanimous, the hearing itself was marked by emotional pleas from breast cancer patients who believe they are benefitting from bevacizumab treatment.   The recommendation is not binding and a final decision is expected in September. It also does not affect insurance coverage or availability at this time, or the drug's approval for other cancer types.

"We know this drug has activity in some women," said David Mintzer, MD, clinical associate professor and chief of hematology/oncology, Pennsylvania Hospital. "We have all seen it and we know that activity stops when you stop giving the drug, but we just know now how to predict which women will get that benefit."

Abstracts can be found on the 2011 ASCO meeting website.

Learn more about breast cancer treatment at Penn’s Abramson Cancer Center.

Are you at risk for breast cancer? Attend Penn Women’s Cancer Conference – Focus on Your Risk of Breast/Ovarian Cancer

Are you a breast cancer survivor? Attend the Penn Women’s Cancer Conference – Life after Breast Cancer 

Coming up next, Understanding the Biology of Breast Cancer.

Thursday, September 15, 2011

Research Community Rates Penn Breakthrough as 'Exceptional'

Bruce Levine, PhD, research associate professor at the Perelman School of Medicine, and facility director, Clinical Cell and Vaccine Production Facility at Penn's Abramson Cancer Center, shares some of the response to the findings of "serial killer" T cells to treat cancer.

Our recent breakthrough in using genetically modified T cells to destroy cancer cells announced continues to draw attention nationally and around the world.

Genetically modified T cells
The research, published simultaneously in the New England Journal of Medicine (NEJM) and Science Translational Medicine in August, is the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors. The study shows sustained remissions of up to a year among a small group of patients with advanced chronic lymphocytic leukemia (CLL) treated with genetically engineered versions of their own T cells.

Each of our recent reports were selected and evaluated by the Faculty of 1000 (F1000). F1000 identifies and evaluates the most important articles in biology and medical research publications. Articles are selected by a peer-nominated global 'faculty' of the world's leading scientists and clinicians who then rate them and explain their importance.  On average, 1,500 new evaluations are published each month; representing approximately 2 percent of all published articles in the biological and medical sciences.

The comments from the F1000 evaluators follow. While the evaluations highlight the technical research, both evaluations rated the study as "exceptional."

Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. (N Engl J Med 2011 Aug 10), evaluated by Christopher Thanos.
Evaluation details: Exceptional [10] New Finding, Technique

Review: This exceptional article investigated a possible avenue for the treatment of chronic lymphoid leukemia (CLL). The authors used a lentivirus system to infect harvested T cells with a vector that expresses a chimeric protein consisting of an extracellular, anti-CD19 scFv fused to intracellular CD137 and CD3 signalling domains. T cells expressing this chimeric anti-CD19-CD137-CD3 fusion protein were then administered back to a CLL patient and the results were profound. There was massive proliferation of these engineered T cells (>1000X) after administration to the patient, and, by day 23, there was no evidence of CLL in the patient's bone marrow (complete remission).

T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in  patients with advanced leukemia. (Sci Transl Med 2011 Aug 10), evaluated by Joyce Solheim.
Evaluation details: Exceptional [10] Clinical Trial

Review: This article expands on exciting new developments in the use of genetically modified T cells expressing antibody-binding domains as therapies against malignancies. As an accompaniment to their recent case report in the New England Journal of Medicine on the amazing impact of T cells expressing a CD19-specific chimeric antigen receptor, the authors have here provided a more detailed analysis. In this article, they describe the expansion and trafficking of the T cells that they have used to target chronic lymphocytic leukemia, and they delineate the immune responses (including the establishment of T cell memory and prolonged effector function). The clinical effects noted by the authors were impressive in all three patients, although the side effects observed were also quite significant. The specific strategies used by these investigators in their production of the modified T cells have yielded new clues about how complex immune responses in humans can be driven, and have surely laid the groundwork for many future clinical trials, particularly for B cell malignancies.

Senior author of the NEJM paper is Carl June, MD, director of translational research and professor of pathology and laboratory medicine at the Abramson Cancer Center, who led the work. Co-principal investigator is David Porter, MD, professor of medicine and director of Blood and Marrow Transplantation. Co-authors include Bruce Levine, PhD; Michael Kalos, PhD, and Adam Bagg, MD; all from Penn Medicine.

Drs. Kalos and Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include Drs. June, Porter and Bagg and Sharyn Katz, MD, from Penn and Stephan Grupp, MD, PhD, Children's Hospital of Philadelphia.

Wednesday, September 14, 2011

Integrative Medicine Enhances Quality of Life for Patients (Post 2 of 2)


Lorraine Gordon is a patient advocate for people with melanoma. Her family established the Roger A. Gordon Melanoma Research Fund in 2007 following her husband's diagnosis of stage 4 melanoma.  The Gordon family works in conjunction with Penn's Abramson Cancer Center (ACC) to increase melanoma awareness and secure research funding. In the second of two posts, she talks about the recent ACC-sponsored Focus On Integrative Medicine and Wellness Conference.

In my first post, I talked about how patients with cancer and cancer survivors are using integrative therapies to improve their quality of life during cancer treatment.  This time I want to share with you the message of two guest speakers, Daniel Gottlieb, PhD, and Michael Baime, MD.

Dr. Gottlieb was in a near fatal automobile accident in 1979, which left him paralyzed from the chest down.  A noted author, columnist, and radio host, his greatest gift to his audience is the understanding that all humans long for human contact, compassion and understanding. While he has not had cancer, he has been through this medical journey. He is a survivor, and all of us attending the program were inspired, motivated and moved by his presentation.
Michael Baime, MD, speaking at
the Focus On: Integrative Medicine and
Wellness Conference

“That nowhere place, where things come out of nowhere, it’s everywhere,” Dr. Gottlieb said.  "People with cancer feel different, isolated. Others look at you differently, you feel alone. There is a difference between the mind and the body: A disconnect between who you were and who you are now. Let go! Learn to tolerate your own vulnerability. You feel as vulnerable as you are."

Michael Baime, MD, is clinical associate professor of medicine at Penn and director of the Penn Program for Mindfulness.  A nationally recognized expert in stress management, he has created a variety of programs for patients in all stages of treatment and recovery for Penn's Abramson Cancer Center.

Dr. Baime shared his own experiences with mindfulness and its role in dealing with his own vision problems.
“You are totally alive, NOW,” he said. "You may wonder how you can be OK. You say, 'I had cancer: I’m always looking over my shoulder.' Let go! We have to celebrate what we have NOW. We don’t have to hope, because we have this moment of NOW. Do something about making the most for yourself. Believe it is possible. Take a chance.

"Mindfulness brings all of your awareness into the present moment," Dr. Baime said. "You can’t wait for the right moment or worry about tomorrow. You are present in the present moment. Letting go has to be conscious and mindfulness is the key to your survival."

Penn's Integrative Medicine and Wellness Program educates and empowers patients to actively manage symptoms and side effects of conventional cancer treatments (such as nausea, vomiting, fatigue and joint pain) in order to maximize the benefits of conventional treatments while maintaining desirable quality of life. Integrative therapies and complementary and alternative medicine are not a replacement for conventional cancer treatment.

Visit the Abramson Cancer Center website for more information about Integrative Medicine and Wellness and to view the podcasts of the 2011 Focus On Integrative Medicine and Wellness conference. 

Wednesday, September 7, 2011

Integrative Medicine Enhances Quality of Life for Patients (Post 1 of 2)

Lorraine Gordon is a patient advocate for people with melanoma. Her family established the Roger A. Gordon Melanoma Research Fund in 2007 following her husband's diagnosis of stage 4 melanoma.  The Gordon family works in conjunction with Penn's Abramson Cancer Center (ACC) to increase melanoma awareness. In the first of two posts, she talks about the recent ACC-sponsored Focus On Integrative Medicine and Wellness Conference.



“The difference between traditional and integrative care is like rain versus the sun shining.”
— Joseph Carver, MD, chief of staff, Abramson Cancer Center

I didn't know a lot about integrative medicine and I was impressed and touched by this uplifting and supportive conference. Many patients said they feel they have greater control of their illness and develop new ways of coping with the distress and uncertainty of their illness using integrative medicine. Had we known about these therapies I think my family's experience would have been quite different.

Integrative medicine and complementary and alternative therapies focus on the whole person. Therapies are usually performed by practitioners outside the conventional system in combination with traditional treatments.

Attendees at the Abramson Cancer Center's
Focus On: Integrative Medicine and Wellness Conference
Based on a recent Penn study, an estimated 66.5 percent of cancer survivors have used integrative therapies to improve their quality of life during cancer treatment.

Complementary and alternative medicine (CAM) refers to the use of non-conventional therapies that complement conventional medicine, including:
Jun Mao, MD, MSCE, assistant professor and director of integrative medicine at Penn, and the conference chair, is a licensed acupuncturist.  He told us that like all complementary therapies, acupuncture is not used as a primary cancer treatment.

"Acupuncture is used in combination with chemotherapy and/or radiation therapy," Dr. Mao said.  "You need to have the courage to try something new and be comfortable with the concept.  After receiving chemo or radiation you can be very fatigued, but acupuncture can help you get more energy."

Kathryn Schmitz, PhD, MPH, associate professor at the Perelman School of Medicine at the University of Pennsylvania and a member of the Abramson Cancer Center’s Cancer Prevention and Control Research Program, discussed the benefits of exercise. As an exercise interventionist who has led multiple trials, she told us exercise makes the journey very different.

Her research has shown:
  • 180 minutes of walking each week reduces the reoccurrence of breast cancer.
  • Survivor risk is cut in half by exercise.
She recommends patients try to exercise between treatments if they are not too tired or sick. Dr. Schmitz has performed extensive research into the benefits of exercise for breast cancer patients. Dr. Schmitz heads the Strength After Breast Cancer Program, a physical therapy program for breast cancer survivors.

Kimberly Fleisher, MSEd, RMT, founder and director of the Reiki School and Clinic in Philadelphia and leader of the Reiki volunteer program at Penn, said it is OK to be skeptical about complementary therapies. She said Reiki is a state of internal balance and harmony and does not involve manipulation, invasiveness or touching.  It encourages:
  • Peace
  • Nurturing
  • Nourishing
  • Balance
Gabriel Rocco, MA, is a staff instructor for  Penn's Program for Mindfulness and teaches classes based on the practice of mindfulness meditation. To help begin healing from within, he told us to find a comfortable position while finding the source of our own healing.  Letting go of unnecessary tensions allows us to connect with our own hearts and be at peace with our compassion. We must take care of ourselves as we would take care of a loved one, with the same compassion.

This conference really was an amazing experience for me. In the next post I will talk about two speakers and how they encouraged us to "live in the moment."

Penn's Integrative Medicine and Wellness Program educates and empowers patients to actively manage symptoms and side effects of conventional cancer treatments (such as nausea, vomiting, fatigue and joint pain) in order to maximize the benefits of conventional treatments while maintaining desirable quality of life. Integrative therapies and complementary and alternative medicine are not a replacement for conventional cancer treatment.

Visit the Abramson Cancer Center website for more information about Integrative Medicine and Wellness and the 2011 Focus On Integrative Medicine and Wellness conference.
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