Small Cell Lung Cancers Form Chemotherapy-Resistant Circulating Tumor Spheres

MedicalResearch.com Interview with:

Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna 

Prof. Hamilton

Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna

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

Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.

Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs – if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.

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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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Precision Therapy In Early Stages For Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Eran Andrechek, PhD

Eran Andrechek, PhD Associate Professor Department of Physiology Michigan State University East Lansing, MI

Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI 

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

Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment.  Other types can be treated with personalized medicine, resulting in better outcome.  For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself.  The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.

The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options.  Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.  Continue reading

For African American Women, Breast Cancer Symptoms Worsen During Initial Treatments

MedicalResearch.com Interview with::

Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN Acute and Tertiary Care Department University of Pittsburgh School of Nursing

Margaret Rosenzweig

Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN
Acute and Tertiary Care Department
University of Pittsburgh School of Nursing

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

Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for  African American women with breast cancer. The purpose of the current study was to:

1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and

2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.

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ER-beta May Identify Breast Cancer Patients For Whom Chemotherapy is Sufficient

MedicalResearch.com Interview with:
Helena Jernström, PhD
Associate Professor in Experimental Oncology
Study Coordinator for Graduate studies Division of Oncology and Pathology
Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University
Division of Oncology and Pathology, Department of Clinical Sciences, Lund
Lund University Cancer Center/Kamprad
Lund, Sweden

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

Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.

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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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Breast Cancer: 21-gene assay Can Help Choose Neoadjuvant Therapy

MedicalResearch.com Interview with:

Harry D. Bear, MD, PhD Walter Lawrence, Jr. Distinguished Professor of Oncology; Chair, Division of Surgical Oncology, Department of Surgery; Professor, Departments of Surgery, Microbiology & Immunology, VCU School of Medicine; Director, Breast Health Center, VCU Massey Cancer Center; Medical Director Massey Cancer Center Clinical Trials Office Virginia Commonwealth University

Dr. Harry Bear

Harry D. Bear, MD, PhD
Walter Lawrence, Jr. Distinguished Professor of Oncology;
Chair, Division of Surgical Oncology, Department of Surgery;
Professor, Departments of Surgery, Microbiology & Immunology,
VCU School of Medicine; Director, Breast Health Center,
VCU Massey Cancer Center; Medical Director
Massey Cancer Center Clinical Trials Office
Virginia Commonwealth University

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

Response: This was based on the utility of using the 21-gene assay of breast cancers to guide the decision to add chemotherapy to the adjuvant therapy for patients with hormone-responsive breast cancer.

We hypothesized that the Recurrence Score could be used to guide the choice of neoadjuvant therapy for women with hormone responsive breast cancer who needed pre-operative treatment to shrink the tumor and make breast conservation feasible.

The main findings were:
1) Using the 21-gene RS assay to guide  neoadjuvant therapy is feasible.
2) Clinical and pathologic responses were not negatively impacted by using neoadjuvant hormonal therapy in patients with RS<25.
3) Patients whose tumors have a low recurrence score can be safely and effectively treated with hormone therapy alone.

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

Response: These results support the use of the recurrence score to choose hormonal vs. chemotherapy, enabling more personalized care and optimizing outcomes for patients with ER+ early breast cancerwho are candidates for NST.

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

Response: I would like to see a larger prospective trial to build on the evidence from this pilot study that would provide definitive evidence for the use of genomic profiling of breast cancers to guide neoadjuvant therapy.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Disclosure:  Study supported by Genomic Health Inc.

Citation:
39th Annual SABCS 2016
Abstract: P2-10-04
Poster: “Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial”
Authors: Bear HD, Wan W, Robidoux A, Rubin P, Limentani S, White, Jr. RL, Granfortuna J, Hopkins JO, Oldham D, Rodriguez A, Sing AP.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Breast Cancer: PARP Inhibitor Veliparib Has Potential To Enhance Platinum Chemotherapy in Recurrent or Metastatic Disease

MedicalResearch.com Interview with:
Vince Giranda, M.D., PH.D.
Project Director
AbbVie Oncology Development

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

Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate.

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Low-Dose Regularly Timed Chemotherapy May Keep Some Resistant Cancers in Check

MedicalResearch.com Interview with:

Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan

Dr. Kelvin K. Tsai

Kelvin K. Tsai, MD, PhD
Associate Investigator and Attending Physician
Laboratories for Tumor Aggressiveness and Stemness
National Institute of Cancer Research, National Health Research Institutes
Associate Professor and Principal Investigator
Laboratories of Advanced Molecular Therapeutics
Graduate Institute of Clinical Medicine
College of Medicine, Taipei Medical University, Taiwan

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

Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers.

We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.

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MARIANNE Study of HER2+ Metastatic Breast Cancer: Trastuzumab Emtansine With or Without Pertuzumab vs Trastuzumab Plus Taxane

MedicalResearch.com Interview with:

Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology

Dr. Edith Perez

Edith Perez, MD
Vice President and Head of U.S. Medical Affairs
Genentech BioOncology

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

Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.

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