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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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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Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

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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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Predictors of Chemosensitivity in Triple Negative Breast Cancer

MedicalResearch.com Interview with:

Christos Hatzis, PhD Assistant Professor of Medicine Director of Bioinformatics, Breast Medical Oncology Yale Comprehensive Cancer Center Yale School of Medicine New Haven, CT

Dr. Christos Hatzis,

Christos Hatzis, PhD
Assistant Professor of Medicine
Director of Bioinformatics, Breast Medical Oncology
Yale Comprehensive Cancer Center
Yale School of Medicine
New Haven, CT

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

Response: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.

Identifying chemosensitive triple negative breast cancers could significantly impact
the survival of patients with these difficult to treat cancers until novel targeted
therapies become available. We hypothesized that genomic somatic aberrations may
provide important molecular clues about chemosensitivity in TNBC. Our study used
a carefully selected cohort of 29 uniformly treated TNBC patients who either achieved
pathologic complete response (pCR) or had extensive residual disease after neoadjuvant
anthracycline/taxane chemotherapy.

MedicalResearch.com: What are the main findings?

Response: We sequenced the coding genomic DNA of TNBC tumors and compared the somatic mutations found in the two groups at the two extremes of the chemosensitivity spectrum.

Our analysis revealed that, although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor
(AR) and FOXA1 pathways were much more sensitive to chemotherapy.
We also found that mutations that lowered the levels of functional BRCA1 or BRCA2 RNA
were associated with significantly better survival outcomes; we derived a BRCA
deficiency signature to define this new, highly chemosensitive subtype of TNBC.
BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as
more clonal tumors with a higher number of mutations per clone, and are also associated
with a higher level of immune activation, which may explain their greater chemosensitivity.

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

Response: Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens.

The newly defined RNA-based BRCA-deficient subtype includes up to 50% of the
Triple negative breast cancer tumors that appear to be immune primed, and it would be of interest to investigate combinations of chemotherapy with immunotherapies, which could provide clinical benefit for these patients. Although our study showed concordant results in three different datasets, our key findings need to be further validated in a larger, prospectively designed study with archival samples.

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

Response: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in Triple negative breast cancer and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. Our results suggest that the combination of immunotherapies with ACT chemotherapy or PARP inhibitors might be an effective strategy for treating BRCA-D tumors.

The strong connection of ACT chemosensitivity and immune activity with a new transcriptionally defined BRCA-D phenotype could help inform future therapeutic strategies for TNBC patients.

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

Citation:

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic AnalysisTingting Jiang,Weiwei Shi,Vikram B. Wali,Lőrinc S. Pongor,Charles Li,Rosanna Lau,Balázs Győrffy,Richard P. Lifton,William F. Symmans,Lajos Pusztai,Christos Hatzis

PLOS Medicine Published: December 13, 2016http://dx.doi.org/10.1371/journal.pmed.1002193

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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How Does Tailoring Chemotherapy Affect Breast Cancer Survival?

MedicalResearch.com Interview with:
Jonas Bergh M.D, Ph.D. F.R.C.P. (London, UK)
Professor of Oncology (Mimi Althainz´donation)
Director Strategic Research Program in Cancer
Karolinska Institutet
Radiumhemmet, Karolinska University Hospital
Stockholm, Swede

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

Response: Present standard dosing of chemotherapy is aiming at a similar dose for each individual (similar effects and side-effects) , by calculating the dose per mg/m2 based on a formula originally established by du Bois (1916), based on body surface calculations by measuring height and weight. As I recall it, this was done on nine individuals…
However, the body surface has very little to do with how you cytotoxic drugs are metabolized and excreted… in practice this means that chemotherapy dosing based on body surface area will result in under- or overdosing of quite a proposition of the patients… Please Google/run a PubMed research on H. Gurney in Australia, he and other have really expressed their concerns with our present chemotherapy dosing strategies.

In our prospective adjuvant chemotherapy study of high risk breast cancer patients we tested a very well established standard chemotherapy regimen given every third week (FEC100 mg/m2 x 3+ docetaxel 100 mg/m2 x3) vs. our experimental arm given very second week in a dose dense fashion. We also tried to optimize the dosing, aiming at avoiding overdosing some patients at the first course and increase the dose for those without predefined toxicities. Therapy duration was similar in both groups, 15 weeks. Please see the end of the discussion in JAMA for the shortcomings with our study.

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Antiemetic Drugs Can Be Overprescribed To Chemotherapy Patients

MedicalResearch.com Interview with:
Ayako Okuyama, RN, PHN, MW, PhD
Center for Cancer Control and Information Services
National Cancer Center, Japan

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

Response: Chemotherapy-induced nausea and vomiting (CINV) is a major concern for chemotherapy patients. Despite widespread concern, not all chemotherapeutic drugs cause severe CINV. Our study illustrated that the potential for overuse of prophylactic antiemetics for chemotherapy with minimal and low emetic risks according to the antiemetic guidelines.

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Localized Prostate Cancer: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy

MedicalResearch.com Interview with:

Professor Jenny Donovan  PhD   OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for  Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK

Prof. Jenny Donovan

Professor Jenny Donovan  PhD
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Bristol, UK

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

Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.

The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).

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