Author Interviews, Breast Cancer, Immunotherapy / 22.12.2016

MedicalResearch.com Interview with: Joyce O'Shaughnessy, MD Co-Chair, Breast Cancer Research Texas Oncology-Baylor Charles A. Sammons Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The MONALEESA-2 trial is a Phase III, randomized, double-blind, international study of LEE011 in combination with letrozole vs. letrozole alone, in postmenopausal women with HR+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease. Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experience recurrence of their initial breast cancer. We analyzed a pre-defined subgroup of women with de novo HR+/HER2- advanced breast cancer to better understand the response of LEE011 plus letrozole in this patient population. In the de novo advanced breast cancer patient sub-group, progression free survival was significantly prolonged; LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267–0.750]). The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone. Most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common all-grade adverse events (≥30% of patients with de novo advanced breast cancer) in the LEE011 plus letrozole arm were neutropenia (70.2%), nausea (48.2%), fatigue (42.1%), alopecia (39.5%), and leukopenia (31.6%). (more…)
Author Interviews, Breast Cancer, Chemotherapy, Mammograms, MD Anderson, Surgical Research / 12.12.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 12.12.2016

MedicalResearch.com Interview with: Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The goal of this study was to understand molecular changes which occur when breast cancers metastasize to the brain, with the eventual of identifying new therapeutic strategies. Brain metastases occur in 10-15% of patients with metastatic breast cancer and are a major clinical challenge. Limited therapeutic options exist for patients with brain metastases. We analyzed molecular changes in pairs of patient-matched primary breast cancers and brain metastases. We found that brain metastases tended to have the same intrinsic subtype as the primary breast cancer, however, there were many genes which changes in gene expression and may represent therapeutic targets. The most common change was an increase in ErbB2/HER2 which can be targeted clinically. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016

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. (more…)
Author Interviews, Breast Cancer, Geriatrics, Radiation Therapy / 23.11.2016

MedicalResearch.com Interview with: Emily C. Daugherty, MD Upstate Medical University Radiation Oncology Resident, PGY-4 MedicalResearch.com: What is the background for this study? Response: Adjuvant radiation following breast conserving surgery has been well established in the management of early-stage breast cancer as it has been shown to decrease the incidence of ipsilateral breast tumor recurrences and also reduce breast cancer mortality. Large prospective trials have shown for elderly patients with favorable, ER positive pathology, omission of radiation after lumpectomy can be considered. However, women with ER negative disease were typically not included in these trials and given their higher risk for relapse as well as lack of effective endocrine therapy, we hypothesized that adjuvant radiation would benefit women over 70 years with early-stage, ER negative tumors. (more…)
Author Interviews, Breast Cancer, PNAS, Stem Cells / 20.11.2016

MedicalResearch.com Interview with: Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: One mysterious and devastating aspect of breast cancer is that it can reemerge abruptly, often as metastatic disease, in patients many years after an apparent eradication of the primary tumor. The sudden reappearance of cancer has been termed relapse and is thought to occur because a minimal number of resilient tumor cells are able to evade frontline therapies and linger in an undetectable/dormant state somewhere in the body for an unpredictable amount of time. Then, for reasons that remain unclear, these same dormant cells awaken and rapidly grow, and produce almost invariably fatal cancerous lesions. The therapeutic challenges of tumor dormancy and need to decode the underlying mechanisms involved are apparent. Cancer cell behavior is strongly influenced by various non-malignant cell types that are found within the tumor mass itself and that help make up the tumor microenvironment (TME). In particular, bone marrow-derived mesenchymal stem/stromal cells (MSCs), which are actively recruited into the tumor stroma, directly interact with carcinoma cells and significantly impact cancer progression, although the role of MSCs in tumor dormancy remains ill-defined. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 19.11.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Karolinski Institute / 09.11.2016

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. (more…)
Author Interviews, Breast Cancer, Vaccine Studies / 30.10.2016

MedicalResearch.com Interview with: Josef Singer MD, PhD Comparative Medicine Messerli Research Institute of the University of Veterinary Medicine Medical University Vienna University Vienna, Austria & Department for Comparative Immunology and Oncology Institute of Pathophysiology and Allergy Research Medical University Department of Internal Medicine II University Hospital Krems Karl Landsteiner University of Health Sciences Krems, Austria  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Immunotherapy of cancer has gained increasing interest in treatment of oncologic patients. Especially passive immunotherapy with monoclonal antibodies against tumor-associated antigens has been very successful due to good response rates with relatively moderate side effects compared to conventional chemotherapy. Trastuzumab, an antibody against the human epidermal growth-factor receptor-2 (HER-2), is widely applied for the treatment of metastatic breast cancer. Trastuzumab leads to longer progression-free and overall survival in patients with HER-2 positive disease. However, monoclonal antibody therapies have to be repetitively applied, which represents a risk for infusion-related side effects and, due to the high costs, a massive burden for social security systems. Our aim was to replace the passive immunotherapy by a vaccine actively inducing patients´ own antibodies with the same specificity as trastuzumab. A novel mimotope library platform enabled the development of a HER2-specific cancer vaccine: Mimotopes are small peptides that are able to mimic antibody epitopes on tumor-associated antigens, in our case the trastuzumab antigen on HER-2. We use Adeno-associated-viruses (AAV) as carriers for our HER2 vaccine as they are highly immunogenic and safe. We could demonstrate that this HER-2 mimotope AAV-vaccine induced antibodies against human HER- 2 similar to the clinically used trastuzumab. In a mouse tumor model the HER-2 mimotope AAV vaccine was able to delay the growth of tumors significantly. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, ESMO / 18.10.2016

MedicalResearch.com Interview with: Corey Pelletier PhD Director, Health Economics & Outcomes Research Celgene Corporation Summit, NJ MedicalResearch.com: What is the background for this study? What are the main findings? Response: In a phase III clinical trial, ABRAXANE demonstrated significant improvement in ORR vs paclitaxel in patients with metastatic breast cancer. Celgene initiated this study because limited data exist on the comparative effectiveness of ABRAXANE vs paclitaxel for patients with metastatic breast cancer, including HR+/HER2- and triple negative (TN) metastatic breast cancer (MBC), in a real-world setting. This study used a U.S. based electronic medical record (EMR) dataset to evaluate the real-world comparative effectiveness of second-line ABRAXANE vs paclitaxel in patients with MBC and included patients with HR+/HER2- or TN MBC. This study also assessed adverse events and use of supportive care in this patient population. The median time to treatment discontinuation (TTD) for ABRAXANE vs paclitaxel was 4.50 vs 2.83 months (adjusted P<0.0001*) in all patients. Patients with HR+/HER2- or TN MBC had similar TTD. The median time to next treatment (TTNT) in all patients was 5.9 vs 4.2 months (adjusted P=0.2140*) for ABRAXANE vs paclitaxel, respectively. Patients receiving ABRAXANE had less fatigue, neuropathy, and anemia compared to patients receiving paclitaxel. Patients treated with ABRAXANE also used less antiemetics, and had fewer treatments for hydration or allergic reaction compared to those treated with paclitaxel. Patients treated with paclitaxel used less GCSF and had fewer treatments for bone loss compared to those treated with ABRAXANE. *TTD and TTNT were adjusted for age, number of metastases, targeted agent use, adjunctive chemotherapy, HER2 status, TN status, and CCI score without age. (more…)
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 17.10.2016

MedicalResearch.com Interview with: Melanie Royce, MD, PhD Professor of Medicine University of New Mexico School of Medicine Director of the Breast Multidisciplinary Clinic and Program UNM Cancer Center. Albuquerque, NM 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/HER2-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the Phase II BOLERO-4 clinical trial, presented as an oral presentation at the 2016 European Society for Medical Oncology (ESMO) annual meeting, show preliminary evidence that everolimus in combination with letrozole is effective in treating women with HR-positive/HER2-negative advanced breast cancer in the first-line setting. With follow up of 17.5 months, the median progression-free survival (PFS) is not yet reached. At six months, 83.6% (95% CI: 77.3-88.2%) of women taking everolimus plus letrozole in the first-line setting were without disease progression, and 71.4% (95% CI: 64.0%-77.5%) did not have disease progression at twelve months. Safety findings from BOLERO-4 are consistent with previous studies of everolimus in advanced breast cancer, with the most common adverse events being stomatitis (67.8%), weight loss (42.6%) and diarrhea (36.1%). These adverse events were mostly grade 1 or 2 in severity1. (more…)
Author Interviews, Breast Cancer, Heart Disease, JAMA / 12.10.2016

MedicalResearch.com Interview with: Husam Abdel-Qadir, MD, FRCPC, DABIM (Cardiology and Internal Medicine) Graduate student, Clinical Epidemiology and Health Care Research Elliot Philipson Clinician Scientist Training Program University of Toronto MedicalResearch.com: What is the background for this study? Response: Breast cancer is the most common malignancy among North American women. The successes of screening and treatment have led to a marked increase in the number of breast cancer survivors, whose cardiovascular health is becoming of prime concern. Many recent publications have raised alarm about the incidence of cardiovascular abnormalities after breast cancer treatment. However, there is a paucity of data about the frequency of death from cardiovascular disease rather than breast cancer. Contemporary estimates of the incidence of competing risks like cardiovascular disease are important to guide discussions about prognosis, subsequent follow-up, and survivorship plans. It is important that such incidence estimates are generated using methodology that appropriately accounts for competing risks to avoid providing results that are biased upwards. (more…)
Author Interviews, Breast Cancer, ESMO / 12.10.2016

MedicalResearch.com Interview with: Judith Balmaña MD Medical Oncology Hospital Vall d’Hebron and Vall d’Hebron Institute of Oncology Barcelona, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Tumors  with brca1 or brca2 mutations share homologous recombination repair deficiency, which confers sensitivity to different types of dna damaging agents. An understanding of the role of brca1 and brca2 in the repair of double-stranded dna damage opened a window of opportunity for treating brca mutation–associated cancers with targeted therapies. Lurbinectedin is a trabectedin analog that specifically binds to cg-rich motifs with a selective mechanism of action: in living cells, lurbinectedin inhibits active transcription by degradation of elongating rna polymerase ii. This process occurs specifically on activated genes and is associated with the formation of double strand dna breaks and the collapse of replication forks. In addition, lurbinectedin exerts some antitumoral effect in the microenvironment by inhibiting the transcription of selected cytokines by tumor-associated macrophages, abrogating their protumoral properties. Observations that lurbinectedin was active against homologous-recombination-deficient cell lines led us to test it in patients with metastatic breast cancer having deleterious germline brca mutations. (more…)
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 10.10.2016

MedicalResearch.com Interview with: Gabriel N. Hortobagyi, MD, FACP, F.A.S.C.O. Professor of Medicine Nellie B. Connally Chair in Breast Cancer Department of Breast Oncology Co-Director, Multidisciplinary Breast Cancer Research Program University of Texas MD Anderson Cancer Center Houston, Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: MONALEESA-2 is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer. The primary efficacy results from the pivotal MONALEESA-2 study show LEE011 (ribociclib) plus letrozole significantly extended progression-free survival (PFS) compared to a standard of care, letrozole, as a first-line treatment in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (HR= 0.556; 95% CI: 0.429-0.720; p=0.00000329)1. The results demonstrate that LEE011 plus letrozole reduced the risk of death or progression by 44% over letrozole alone, significantly extending PFS across all patient subgroups. More than half of women with measurable disease taking LEE011 plus letrozole saw their tumor size shrink by at least 30% during treatment (overall response rate (ORR) in patients with measurable disease = 53% vs 37%, p=0.00028)1. (more…)
Author Interviews, Breast Cancer, Race/Ethnic Diversity / 04.10.2016

MedicalResearch.com Interview with: Bijou R. Hunt,  MA Sinai Urban Health Institute, Sinai Health System Chicago, IL  MedicalResearch.com: What is the background for this study? Response: Breast cancer is the most commonly diagnosed cancer in Hispanic women, as well as the leading cause of cancer death for this group. Research has shown that there are differences by Hispanic subgroup in various causes of death, including cancer, but we haven’t seen data on breast cancer specifically among Hispanic subgroups. The most important question we wanted to address with this study was: do breast cancer prevalence and mortality vary by Hispanic subgroup? (more…)
Author Interviews, Breast Cancer, Cancer Research, Education / 30.09.2016

MedicalResearch.com Interview with: Adam Brufsky, MD, PhD, FACP Medical Director of the Women's Cancer Center University of Pittsburgh Medical Center MedicalResearch.com: What is the background for this study? What are the main findings?
  • The Make Your Dialogue Count survey was conducted by Harris Poll on behalf of Novartis between June 20 and August 22, 2014. A total of 359 surveys were collected among women 21 years+ living with advanced breast cancer in addition to 234 caregivers of women with advanced breast cancer and 252 licensed oncologists who treat at least five advanced breast cancer patients per month within the United States. Novartis conducted the survey with guidance from oncologists, patient advocacy experts and a psychologist to better understand the dialogue around treatment goals and decisions that takes place among advanced breast cancer patients, caregivers and oncologists.
  • Main survey findings show communication gaps exist in discussions between patients and oncologists, particularly around treatment plans and goals.
  • 89% of patients and 76% of oncologists said that it’s important or very important to discuss long-term treatment plans beyond the current recommended treatment at their initial advanced breast cancer diagnosis. Yet, 43% of patients reported that this did not take place.
  • 70% of patients and 65% of oncologists said that it’s important or very important to refer patients to support services at their initial advanced breast cancer diagnosis. Yet, only 36% of patients reported that this was something their doctor did.
  • 23% of oncologists said that at times their emotions have kept them from sharing certain information with their advanced breast cancer patients, and 27% of oncologists said that, in certain situations, they do not discuss with patients the fact that advanced breast cancer is incurable.
(more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Nature, Technology / 23.09.2016

MedicalResearch.com Interview with: Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science and Assistant professor of medicine Brigham and Women's Hospital With co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron MedicalResearch.com: What is the background for this study? What are the main findings? Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer. In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis. Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells. My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis. Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis. (more…)
Author Interviews, Breast Cancer, Cancer, Genetic Research, UT Southwestern / 23.09.2016

MedicalResearch.com Interview with: Roshni Rao, M.D Breast Surgery University of Texas Southwestern MedicalResearch.com: What is the background for this study? What are the main findings? Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer. TNBC is more common in young, African American women, but can be found in other ethnic groups as well. This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer. (more…)
Author Interviews, Breast Cancer, JAMA / 15.09.2016

MedicalResearch.com Interview with: Tehillah S. Menes, MD Department of Surgery Tel Aviv-Sourasky Medical Center Tel Aviv, Israel MedicalResearch.com: What is the background for this study? Response: Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. The diagnosis is made by a biopsy showing a uniform proliferation of cells lining the ducts of the breast. These cells have monomorphic round nuclei and characteristically fill only part of the involved duct. Women diagnosed with ADH are recommended to undergo increased surveillance and offered chemoprevention (i.e. Tamoxifen) for risk reduction. Most studies reporting on the risk of subsequent breast cancer in women with ADH were done prior to the wide use of screening mammography and percutaneous needle biopsy. Our study examined 10-year risk of invasive breast cancer in women diagnosed with ADH (by needle biopsy or excisional biopsy), using data collected by the Breast Cancer Surveillance Consortium (BCSC). (more…)
AACR, Author Interviews, Biomarkers, Breast Cancer / 15.09.2016

MedicalResearch.com Interview with: Eva Gonzalez Suarez, PhD Group Leader Transformation and Metastasis lab. Cancer Epigenetics and Biology Program-PEBC Institut d'Investigació Biomédica de Bellvitge-IDIBELL Hospital Duran i Reynals Avinguda Gran Via de l'Hospitalet, L'Hospitalet de Llobregat-Barcelona-Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, driving osteoclastogenesis. RANK signaling pathway acts as a paracrine mediator of progesterone in mouse and human mammary epithelium. RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remained unknown. Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy in mouse models that closely resemble the clinical disease. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes differentiation of tumor cells into milk-producing cells, as observed during pregnancy. (more…)
Author Interviews, Breast Cancer, Endocrinology, OBGYNE / 13.09.2016

MedicalResearch.com Interview with: Leena Hilakivi-Clarke, PhD Professor of Oncology Georgetown University Washington, DC 20057 MedicalResearch.com: What is the background for this study? Response: About 70% of women who develop breast cancer express estrogen receptors in their cancer. These patients are treated with endocrine therapies that target estrogen receptors. Endocrine therapies are effective in half of the patients, but the other half are resistant to the treatment and recur. Prior to the start of endocrine therapy, there is no way to predict who will respond to it and who will have recurrence of breast cancer. Therefore, it is not known which patients might benefit from an additional therapy to prevent recurrence, and what that additional therapy would entail. We wondered if resistance to endocrine therapy (we used tamoxifen) is pre-programmed by maternal exposure to the estrogenic endocrine disrupting chemical ethinyl estradiol (EE2). Previously, we and others have found that EE2 and other estrogenic compounds, when given during pregnancy, increase breast cancer risk in the female offspring in animal studies and among humans. The current study was done using a preclinical animal model that was used 50 years ago to discover that tamoxifen is an effective endocrine therapy for estrogen receptor positive breast cancer patients. (more…)
Author Interviews, Breast Cancer, JAMA / 08.09.2016

MedicalResearch.com Interview with: Conny Vrieling, M.D., Ph.D. Radiation Oncologist Clinique des Grangettes Geneva MedicalResearch.com: What is the background for this study? Response: In the early ’90s, the EORTC (European Organisation for Research and Treatment of Cancer) ran the “boost no-boost” trial, randomizing 5569 early-stage breast cancer patients, treated with breast-conserving surgery and whole-breast irradiation, between no boost and a 16-Gy boost. A third of the patients were included in a central pathology review. The 10-year follow-up results of this subpopulation showed that young age and high-grade invasive carcinoma were the most important risk factors for ipsilateral breast tumor recurrence (IBTR). In this study, we re-analyzed with long-term follow-up the pathological prognostic factors related to IBTR, with a special focus on the evolution of these effects over time. (more…)
Author Interviews, Breast Cancer / 01.09.2016

MedicalResearch.com Interview with: James R. Lambert, PhD. Department of Pathology University of Colorado Anschutz Medical Campus Aurora, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our laboratory has been investigating a novel small molecule drug, AMPI-109, as a targeted therapeutic agent for triple-negative breast cancer (TNBC). We demonstrated that AMPI-109 is a potent inducer of apoptosis in TNBC cells and that its cell killing activities are largely specific for the TNBC subtype of breast cancer. Through our efforts to identify the molecular mechanism of AMPI-109 action in TNBC cells we identified the oncogenic phosphatase, PRL-3 as a mediator of AMPI-109 action and as a potential direct target of the drug in TNBC cells. Our studies have defined PRL-3 as an oncogenic driver of  triple-negative breast cancer as exemplified by knocking down PRL-3 using shRNAs, or treating TNBC cells with AMPI-109, ultimately results in TNBC cell apoptosis. We thus became interested in elucidating the mechanisms whereby loss of PRL-3 expression, or function, results in cell death. During the course of these investigations we noted that at early times following PRL-3 knock down TNBC cells undergo a period of cell senescence followed by induction of apoptosis. This dynamic reprogramming of  triple-negative breast cancer cell fate was determined to be mediated through signaling events mediated by an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop. TNF-R1, which binds the pro-inflammatory cytokine TNFα, is a widely studied mediator of both cell survival and cell death yet the precise molecular mechanism controlling this toggling effect of TNF-R1 on TNBC cells remained largely unknown. In this report, we demonstrate that PRL-3 is transcriptionally regulated by the pro-inflammatory NF-ĸB pathway in  triple-negative breast cancer cells, and that PRL-3 knock down elicits an autocrine TNF-R1 feedback loop that results in cell cycle arrest and senescence as a pre-determinant to engaging apoptosis of TNBC cells. These studies reveal a previously undescribed mechanism for how PRL-3 influences TNBC cell growth and further increase our understanding of the role of TNFα signaling in the disease. (more…)
Author Interviews, Breast Cancer, Genetic Research, Mental Health Research, Ovarian Cancer, Psychological Science / 31.08.2016

MedicalResearch.com Interview with: Mag. Dr. Anne Oberguggenberger PhD Medizinische Universität Innsbruck Department für Psychiatrie, Psychotherapie und Psychosomatik Innsbruck Austria MedicalResearch.com: What is the background for this study? Response: Genetic counseling and testing is increasingly integrated in routine clinical care for breast- and ovarian cancer (BOC). Knowledge on follow-up psychosocial outcomes in all different groups of counselees is essential in order to improve follow-up care and counselees’ quality of life. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM / 26.08.2016

MedicalResearch.com Interview with: Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, Nature / 25.08.2016

MedicalResearch.com Interview with: Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research MedicalResearch.com: What is the background for this study? What are the main findings? Response: About 85% hormone receptor positive HER2 negative metastatic breast cancer patients show that cancer cells acquire HER2 expression during disease progression. These HER2 positive cells coexist with HER2 negative cancer cells, and these two populations are able to spontaneously oscillate between these two states; in culture and in cancers established in mice. Both HER2 positive and HER2 negative cells form tumors when injected into mice, but HER2 positive cancer cells form tumors more rapidly than HER2 negative tumors. At a molecular level, several growth factor pathways are activated in HER2 positive cancer cells, while activation of the Notch pathway, an embryonic signaling event, is observed in HER2 negative cells. Thus the HER2 positive and HER2 negative cancer cells exhibit differential sensitive to drugs: the HER2 positive cells, which are more proliferative and non-responsive to HER2-targeting agents, are responsive to chemotherapy drugs whereas the HER2 negative tumor cells are sensitive to Notch inhibitors. A combination of chemotherapeutic drugs and notch inhibitors effectively eliminate tumors formed by a mixture of these two population of cancer cells compared to either drug alone. These findings highlight the importance of tumor heterogeneity in cancer progression and drug responses and suggest that targeting all the different populations within cancers is necessary to effectively manage cancer progression. (more…)
Author Interviews, Breast Cancer, Cancer Research, Cost of Health Care, Sloan Kettering, Surgical Research / 18.08.2016

MedicalResearch.com Interview with: Monica Morrow, MD, FACS Chief, Breast Service Department of Surgery Anne Burnett Windfohr Chair of Clinical Oncology Memorial Sloan-Kettering Cancer Center MedicalResearch.com: What is the background for this study? Response: DCIS, ductal carcinoma in situ, intraductal cancer or Stage 0 cancer refers to what some people call the earliest form of cancer we can find and others term “precancerous”. This difference in terms is due to the fact that DCIS lacks the ability to spread to other parts of the body, a fundamental characteristic of cancer. The goal of treatment in DCIS is to prevent progression to invasive cancer which has the ability to spread. DCIS accounted for only 2-3 % of breast cancers seen in the pre-screening mammography era, but it comprises 25-30% of the malignancies detected in screening mammography programs. For this reason it is uncommon in women under age 40, and more commonly seen in women over 50 years of age. Approximately 70% of the women in the US diagnosed with DCIS are treated with lumpectomy (removal of the DCIS and a margin of surrounding normal breast tissue), and additional surgeries to obtain clear, or more widely clear, margins are done in approximately 30% of women. For this reason, the Society of Surgical Oncology, the American Society for Therapeutic Radiation Oncology, and the American Society of Clinical Oncology undertook the development of an evidence based guideline to determine the optimal clear margin for women with DCIS treated with lumpectomy and whole breast radiotherapy. (more…)
Author Interviews, Breast Cancer, Cost of Health Care, Johns Hopkins / 11.08.2016

MedicalResearch.com Interview with: Pedram Argani, M.D. Professor of Pathology and Principal consultant of the Breast Pathology Service Johns Hopkins Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most pathology laboratories, at the request if clinicians, automatically (reflexively) test needle core biopsies containing ductal carcinoma in situ (DCIS) for estrogen receptor (ER) and progesterone receptor (PR). The logic for testing DCIS for these hormone receptors is that, for patients who have pure DCIS that is ER positive after surgical excision, treatment with estrogen blockers like Tamoxifen can decrease the recurrence of DCIS by a small amount, though overall survival (which is excellent) is not impacted. However, there are several factors which suggest that this reflex testing unnecessarily increases costs. • First, the ER/PR results on core needle biopsy do not impact the next step in therapy; namely, surgical excision. • Second, a subset of excisions performed for DCIS diagnosed on core needle biopsy will harbor invasive breast carcinoma, which would than need to be retested for ER/PR. • Third, because ER and PR labeling is often variable in DCIS, negative results for ER/PR in a small core biopsy specimen should logically be repeated in a surgical excision specimen with larger amounts of DICS to be sure that the result is truly negative. • Fourth, many patients with pure DCIS which is ER/PR positive after surgical excision will decline hormone therapy, so any ER/PR testing of their DCIS is unnecessary. • Fifth, PR status in DCIS has no independent value. We reviewed the Johns Hopkins experience with reflex ER/PR testing of DCIS on core needle biopsies over 2 years. We found that reflex core needle biopsy specimen testing unnecessarily increased costs by approximately $140.00 per patient. We found that ER/PR testing in the excision impacted management in only approximately one third of cases, creating an unnecessary increased cost of approximately $440.00 per patient. Extrapolating the increased cost of reflex ER/PR testing of DCIS to the 60,000 new cases of DCIS in the United States each year, reflex core needle biopsy ER/PR testing unnecessarily increased costs by approximately 35 million dollars. (more…)