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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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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First Steps Toward Breast Cancer Vaccine Using HER-2 Mimotope

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

Dr. Josef Singer

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.

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Abraxane Demonstrates Benefit Over Paclitaxel in Metastatic Breast Cancer

MedicalResearch.com Interview with:

Corey Pelletier PhD Director, Health Economics & Outcomes Research at Celgene Celgene Corporation Summit, NJ

Dr. Corey Pelletier

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.

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Combination Everolimus/Exemestane For ER+|HER2- Advanced Breast Cancer

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

Dr. Melanie Royce

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.

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Significant Cardiovascular Mortality Following Early-Stage Breast Cancer

MedicalResearch.com Interview with:

Husam Abdel-Qadir

Dr. Husam Abdel-Qadir

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.

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Anti-Tumor Activity of PM01183 (lurbinectedin) in BRCA1/ 2-associated Metastatic Breast Cancer Patients

MedicalResearch.com Interview with:

Judith Balmana MD Medical Oncology Hospital Vall d’Hebron and Vall d’Hebron Institute of Oncology Barcelona, Spain

Dr. Judith Balmaña

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.

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Ribociclib and Letrozole May Represent Paradigm Shift in Treating HR+ Advanced Breast Cancer

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

Prof. Gabriel N. Hortobagyi

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.

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Breast Cancer Mortality Varies By Latina Subgroups

MedicalResearch.com Interview with:

Bijon Hunt Epidemiologist photographed for Sinai Health System on Wednesday, February 4, 2015 at Mount Sinai Hospital in Chicago, Illinois. Photo credit: Randy Belice

Bijon Hunt

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?

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Survey Reveals Communication Gaps Between Oncologists and Patients With Advanced Breast Cancer

MedicalResearch.com Interview with:

Adam Brufsky, MD, PhD, FACP Medical Director of the Women's Cancer Center University of Pittsburgh Medical Center

Dr. Adam Brufsky

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.

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Scaffold Can Potentially Deliver Therapeutic miRNA To Decrease Breast Cancer Metastases

MedicalResearch.com Interview with:

Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science (IMES) and Assistant professor of medicine Brigham and Women's Hospital And co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva Eitan Friedman, Noam Shomron

Dr. Natalie Artzi

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.

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Genetic Ancestry using Mitochondrial DNA in patients with Triple-Negative Breast Cancer

MedicalResearch.com Interview with:

Roshni Rao, M.D Breast Surgery University of Texas Southwestern

Dr. Roshni Rao

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.

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Risk of breast cancer associated with a diagnosis of atypical ductal hyperplasia may be lower than previously reported

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).

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RANK signaling-blockade reduces breast cancer recurrence by inducing tumor cell differentiation

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

Dr. Eva Gonzalez Suarez

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.

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In Utero Exposure to Ethinyl Estradiol Linked to Tamoxifen Resistance and Breast Cancer Recurrence

MedicalResearch.com Interview with:

Leena Hilakivi-Clarke, PhD Professor of Oncology Georgetown University Washington, DC 20057

Dr. Leena Hilakivi-Clarke

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.

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Breast Cancer: Long-term Prognostic Factors in the Boost vs No Boost Trial

MedicalResearch.com Interview with:

Conny Vrieling, M.D., Ph.D. Radiation Oncologist Clinique des Grangettes Geneva

Dr. Conny Vrieling

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.

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Breaking a Feedback Loop May Trigger Cell Death in Triple Negative Breast Cancer

MedicalResearch.com Interview with:

James R. Lambert, PhD. Department of Pathology University of Colorado Anschutz Medical Campus Aurora, CO

Dr. Jim Lambert

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.

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Genetic Counselling Did Not Increase Anxiety in Breast and Ovarian Cancer Patients

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.

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70-Gene Signature Can Help Identify Early-Stage Breast Cancer Patients Who Do Not Need Chemotherapy

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

Dr. Laura Van’t Leer

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.

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Breast Cancer Cells Can Switch HER2 On and Off, Requiring Combination Treatment

MedicalResearch.com Interview with:

Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research

Dr. Shyamala Maheswaran

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.

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New Guidelines for Surgical Margins After DCIS Breast Cancer

MedicalResearch.com Interview with:

Monica Morrow, MD, FACS Chief, Breast Service, Department of Surgery Anne Burnett Windfohr Chair of Clinical Oncology

Dr. Monica Morrow

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.

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Patients With Newly Diagnosed DCIS Breast Cancer May Not Need Their Core Needle Biopsy Tested for Hormone Receptors

MedicalResearch.com Interview with:

Pedram Argani, M.D. Professor of Pathology and Principal consultant of the Breast Pathology Service Johns Hopkins Medicine

Dr. Pedram Argani

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.

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Risk of Background Changes on Breast MRI Reexamined

MedicalResearch.com Interview with:

Barbara Bennani-Baiti, MD, MS

Dr. Bennani-Baiti

Barbara Bennani-Baiti, MD, MS and

Pascal Andreas Baltzer MD

Dr. P. Baltzer

Pascal Andreas Baltzer MD
Departement of Biomedical Imaging and Nuclear Medicine
Medical University of Vienna
Vienna, Austria

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

Response: Breast MRI ist the most sensitive method for detecting breast cancer. It is currently routinely used in the screening of high-risk patients and as an additional imaging technique in case of inconclusive conventional imaging (mammography and ultrasound).

Besides its high sensitivity for detection of breast cancer, breast MRI further provides functional information about normal breast tissue perfusion. Background parenchymal enhancement (BPE) reflects the perfusion or vascularization of the breast and is generally higher in active breast tissue. High-risk patients harbor breast tissue that is at an elevated risk for breast cancer due to several factors (i.e. mutations such as BRCA1, high familial risk, previous radiation of the chest wall, etc.). After a connection between increased breast cancer odds and elevated BPE has been shown in high-risk patients, the community has since assumed that an elevated background enhancement at breast MRI equates an elevated risk for breast cancer for all women. We have shown that this not true for women that are not considered high-risk. In fact, the only risk factor for women undergoing breast MRI without additional risk factors is age.

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Most Patients With Newly Diagnosed Breast Cancer Don’t Use Social Media For Advice

MedicalResearch.com Interview with:

Lauren P. Wallner, PhD, MPH Assistant Professor, Departments of Medicine and Epidemiology University of Michigan Ann Arbor, MI

Dr. Lauren Wallner

Lauren P. Wallner, PhD, MPH
Assistant Professor, Departments of Medicine and Epidemiology
University of Michigan
Ann Arbor, MI

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

Response: Online communication tools like email and social media could be used to support patients through their cancer treatment decision making and ongoing care. Yet, we know very little about whether and how newly diagnosed cancer patients use these tools and whether using online communication influences patients appraisals of their treatment decision making process.

We surveyed 2,460 women with newly diagnosed breast cancer as part of the iCanCare Study about their use of email, texting, social media and web-based support groups following their diagnosis. Our findings suggest that women who more often used these online communication tools deliberated more about their surgical treatment and were more satisfied with their treatment decision. However, the use of social media in this diverse population was lower than we expected (12%), and was less common in older women, those with less education, and Black and Latina women.

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Is There an Increased Risk of Breast Cancer in Women Who Have IVF?

MedicalResearch.com Interview with:

Alexandra W. van den Belt-Dusebout, PhD Department of Epidemiology The Netherlands Cancer Institute The Netherlands

Dr. Alexandra van den Belt-Dusebout

Alexandra W. van den Belt-Dusebout, PhD
Department of Epidemiology
The Netherlands Cancer Institute
The Netherlands

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

Response: In vitro fertilization (IVF) is commonly used, but because of the relatively recent use of IVF, long-term breast cancer risk is not yet known. Female sex hormones have been shown to affect breast cancer risk. Because sex hormone levels during hormonal stimulation of the ovaries for IVF are up to 10 times higher than in natural cycles, IVF was expected to increase breast cancer risk.
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Breast Density Interpretation Varies Among Radiologists

MedicalResearch.com Interview with:

Dr-Brian-SpragueBrian L. Sprague, PhD
Assistant Professor
Department of Surgery
Assistant Professor
Department of Biochemistry
University of Vermont

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

Response: Having dense breasts makes mammography more difficult to interpret and is also an independent risk factor for developing breast cancer. About half of all U.S. states require that information on the density of a woman’s breasts be made available to her after a mammogram, and in some states the report must also inform such women that there are additional tests, such as breast magnetic resonance imaging (MRI), that may detect breast cancer in women who have dense breasts and normal mammograms.

Such laws are controversial because of the large number of women affected (around 40% of women aged 40-74) and due to a lack of consensus in the medical community regarding the benefits and harms of supplemental screening strategies. An additional concern is the subjective nature of breast density assessment, which is based on the Breast Imaging Reporting and Data System (BI-RADS) that provides four possible categories for breast density.

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Younger Breast Cancer Patients With Radiation and Node Dissection More Likely To Have Post-Op Pain

MedicalResearch.com Interview with:

Jason Busse PhD Department of Anesthesia Department of Clinical Epidemiology & Biostatistics McMaster University Hamilton, ON

Dr. Jason Busse

Jason Busse PhD
Department of Anesthesia
Department of Clinical Epidemiology & Biostatistics
McMaster University
Hamilton, ON

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

Response: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. We found that development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection increases the absolute risk of persistent pain by 21%, and provides the only high yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.

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Prediction of Cancer Outcomes Can Be Improved By Genetic Analysis of Tumor

MedicalResearch.com Interview with:

Ana I. Vazquez PhD Department of Epidemiology and Biostatistics Michigan State University East Lansing, Michigan

Dr. Ana I. Vazquez

Ana I. Vazquez PhD
Department of Epidemiology and Biostatistics
Michigan State University
East Lansing, Michigan

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

Response: Precise predictions of whether a tumor is likely to spread would help clinicians and patients choose the best course of treatment. But current methods fall short of the precision needed. We tested whether breast cancer survival predictions could be improved by profiling primary tumor samples with genomic technologies. We found that predictions based on clinical information, such as cancer stage and subtype, improve when they incorporate comprehensive data on which genes are active in tumor samples compared to non-cancerous tissues from the same patient. This is also true for genome-wide methylation data, which maps the parts of the DNA that carry molecular “tags” that influence gene activation. If developed for use in the clinic, our approach could spare some patients from unneeded chemotherapy.

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Neoadjuvant Endocrine Therapy May Be Alternative to Chemotherapy for Estrogen Receptor–Positive Breast Cance

MedicalResearch.com Interview with:

Aditya Bardia, MD, MPH Massachusetts General Hospital Cancer Center Harvard Medical School Boston, MA

Dr. Aditya Bardia

Aditya Bardia, MD, MPH
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, MA 

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

Response: While endocrine therapy is the recommended therapy for Estrogen Receptor positive (ER+) breast cancer, the role of endocrine therapy in neoadjuvant (pre-surgical) setting is unclear. We performed this systematic review and meta-analysis to comprehensively evaluate the efficacy of neoadjuvant endocrine therapy, both alone and in combination with other therapies, compared to neoadjuvant chemotherapy for localized ER+ breast cancer. We found no statistically significant differences between the two treatments in regards to clinical response, imaging response, rates of breast conservation therapy, and achievement of pathologic complete response.

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GW Radiologist Discusses Implications of Breast Density Notification Laws

MedicalResearch.com Interview with:

Rachel Brem, MD Professor of Radiology and Director of Breast Imaging and Intervention George Washington University School of Medicine.

Dr. Rachel Brem

Rachel Brem, MD
Professor of Radiology and
Director of Breast Imaging and Intervention
George Washington University School of Medicine.

MedicalResearch.com Editor’s note: Many states now have laws regarding patient notification of breast density after mammography screening.
Dr. Brem discusses the background and implications of the new mandatory notification laws.

MedicalResearch.com: What is meant by ‘breast density?’ Is breast density a risk factor for breast cancer? Is breast cancer more difficult to detect in dense breasts?

Dr. Brem: Breast density is a measure used to describe the proportion of fat versus breast tissue, which includes fibrous and glandular tissue. Dense breasts contain more fibrous and glandular tissue and less fatty tissue. This is important because on a mammogram dense breast tissue is white and breast cancer is white. The lack of contrast can make detecting cancer more difficult.

You can only tell if your breasts are dense from the mammogram. You can’t feel dense breast tissue or see it.

An estimated 40 percent of women have dense breast tissue that may mask the presence of cancerous tissue in standard mammography. Dense breast tissue decreases with age, but remains important throughout life. Over 75 percent of women in their 40s have dense breast tissue but over a third of women in their 70s have dense breast tissue.

As breast density increases, mammography sensitivity decreases. This is significant, but we must consider the increased risk of breast cancer in women with dense breast tissue. Women with dense breast tissue have up to a four-fold increased risk of developing breast cancer. So, breast density is essentially the “perfect storm” where the ability to detect cancer decreases while the risk for breast cancer increases. Therefore, optimal approaches to individualized breast cancer screening are needed.

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Women With Breast Cancer Have Different Bacterial Microbiome in Breasts

MedicalResearch.com Interview with:

Gregor Reid, B.Sc. Hons., Ph.D., MBA, ARM, CCM, Dr. HS, FCAHS Director, Canadian Centre for Human Microbiome and Probiotic Research Lawson Health Research Institute London, Ontario, Canada

Dr. Gregory Reid

Gregor Reid, B.Sc. Hons., Ph.D., MBA, ARM, CCM, Dr. HS, FCAHS
Director, Canadian Centre for Human Microbiome and Probiotic Research
Lawson Health Research Institute
London, Ontario, Canada

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

Response: Women who breast feed have reduced risk of breast cancer. Human milk has bacteria passed on to the child. These bacteria reach the breast through the nipple and from the gut via the blood. Lactobacilli and Bifidobacteria, beneficial bacteria, grow well in milk. So, I wondered what if women never lactate or breast feed, could bacteria be there? Could bacteria be in the tissue itself and influence whether you got or did not get cancer. Proving there are bacteria in the actual breast tissue itself was an interesting discovery defying previous beliefs.

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Breast Cancer Surgery Can Be Improved By Turning Patient Over For MRI

MedicalResearch.com Interview with:

Eva C. Gombos, MD Assistant Professor, Radiology Harvard Medical School Brigham and Women’s Hospital

Dr. Eva Gombos

Eva C. Gombos, MD
Assistant Professor, Radiology
Harvard Medical School
Brigham and Women’s Hospital

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

Response: Treatment of early stage breast cancer, breast-conserving therapy (BCT), which consists of lumpectomy followed by whole-breast irradiation, requires re-excision 20 %–40% of patients due to positive margins.

Breast MR is the imaging modality with the highest sensitivity to detect breast cancer. However, patients who undergo breast MR imaging have not experienced reduced re-excision or improved survival rates.

Our hypothesis is that supine (performed with patient lying on her back) MR imaging within the operating room can be used to plan the extent of resection, to detect residual tumor immediately after the first attempt at definitive surgery, and to provide feedback to the surgeon within the surgical suite. The aim of this study was to use intraoperative supine MR imaging to quantify breast tumor deformation and displacement secondary to the change in patient positioning from imaging (prone performed the patient lying on her stomach) to surgery (supine) and to evaluate the residual tumor immediately after BCT.
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Older Breast Cancer Patients Much Less Likely to Receive 21-Gene Recurrence Score Testing

MedicalResearch.com Interview with:

Valentina Petkov, MD, MPH Health Scientist/Program Officer NIH/NCI/DCCPS/Surveillance Research Program

Dr. Petkov

Valentina Petkov, MD, MPH
Health Scientist/Program Officer
NIH/NCI/DCCPS/Surveillance Research Program

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

Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level.

We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30).

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MRI Imaging Links Saturated Fat In Breasts with Aggressive Breast Cancer

MedicalResearch.com Interview with:
Sungheon G. Kim, PhD
Associate Professor
Department of Radiology
NYU Langone and
Researcher at the Center for Advanced Imaging, Innovation, and Research

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

Dr. Kim: The role of fat in breast cancer development and growth has been studied extensively using body mass index (BMI), a measure of whole body fatness, and dietary fat intake in a number of epidemiological studies. However, there is a paucity of studies to assess the role of breast fat itself in breast cancer due to lack of a non-invasive and fast measurement method. Since breast fibroglandular cells are surrounded by breast fat cells, the characteristics of breast fat may have a stronger relationship with breast cancer development and growth than BMI and/or dietary fat. However, it is not trivial to study the role of breast fat, mainly due to the lack of a non-invasive and fast measurement method sensitive enough to important features of breast fat, such as types of fat.

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Opioid-Free Approach To Breast Cancer Surgery Explored

MedicalResearch.com Interview with:
Dr. Sarah Saxena
Université Libre de Bruxelles

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

Dr. Saxena: Opioids are well known analgesics, but like every drug, they do not come without side-effects. Recently, certain studies have been published about an opioid-free approach in bariatric patients. An opioid free approach is possible combining ketamine, lidocaine and clonidine.

We studied this type of approach in breast cancer patients and looked at several factors such as patient comfort pain quality after an opioid free approach vs after an opioid approach. The study showed patients requiring less analgesics after an opioid free approach.

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Breast and Ovarian Cancers May Have Common Epigenetic Origin

MedicalResearch.com Interview with:

Sibaji Sarkar Ph.D Instructor of medicine Boston University School of Medicine Boston

Dr. Sibaji Sarkar

Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston

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

Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.

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Adolescent Diet High in Saturated Fats Linked to Breast Density in Adulthood

MedicalResearch.com Interview with:
Seungyoun Jung, ScD, Fellow and
Joanne F. Dorgan Ph.D., M.P.H., Professor

Department of Epidemiology & Public Health
Division Director Of Cancer Epidemiology
University of Maryland

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

Response: Despite the strong evidence from the animal and experimental studies, the lack of association between fat intake and breast cancer has been observed in epidemiologic studies of adult women. However, the development of breast tissue, which induces rapid structural changes and makes breasts vulnerable to exposures, mostly occurs during adolescence. The effect of dietary fat intake on the breasts, therefore, might be greater at younger than older ages. However, only a few prospective cohort studies have examined the role of fat intake during adolescence in relation to the possible risk of breast cancer later in adulthood. Therefore, we examined the association between adolescent intakes of dietary fat and breast tissue composition as measured by breast density, a strong risk factor for breast cancer, measured among young women in the Dietary Intervention Study in Children 2006 Follow-up (DISC06) study.

MedicalResearch.com: What are the main findings?

Response: We observed that higher intake of saturated fat and lower intake of mono- and polyunsaturated fat during adolescence are associated with higher breast density measured approximately 15 years later.

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

Response: The take home message from our results, if confirmed, is that the diet consumed in early life is important and may confer risk or protective benefits for breast cancer later in adulthood. In particular, adherence to a healthy diet higher in healthy unsaturated fats and lower in saturated fats during youth may contribute to lower breast density, and possibly decreased breast cancer risk.

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

Response: As a future direction of our study, it will be important to see if our results are replicated in a large prospective cohort study and are not attributable to other components in major food sources of different types of fat, and to identify possible underlying mechanism.

MedicalResearch.com: Is there anything else you would like to add?

Response: Breast cancer is the most common cause of cancer incidence and cancer death among women worldwide. However, the established known risk factors for breast cancer, such as age at menarche, age at first full term pregnancy and age at menopause, are not readily modifiable. Although further research is warranted, our result is important as it suggests the promising role of dietary modification during adolescence for promotion of breast health as well as prevention of diabetes, cardiovascular disease and other chronic diseases in adulthood.

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

Citation:

Seungyoun Jung, Olga Goloubeva, Catherine Klifa, Erin S. LeBlanc, Linda G. Snetselaar, Linda Van Horn, and Joanne F. Dorgan. Dietary Fat Intake During Adolescence and Breast Density Among Young Women. Cancer Epidemiology, Biomarkers & Prevention, May 2016 DOI:10.1158/1055-9965.EPI-15-1146

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Breast Cancer Drug May Also Treat Aggressive Leukemia

MedicalResearch.com Interview with:

Dr. Iris Z Uras

Dr. Uras

Dr. Iris Z Uras and Univ.-Prof. Dr. Veronika Sexl

Univ.-Prof. Dr. Veronika Sexl

Dr. Sexl

Institute of Pharmacology and Toxicology
University of Veterinary Medicine
Vienna

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

Response: Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Patients suffering from AML have poor prognosis and high mortality rate despite considerable advances in chemotherapy and hematopoietic stem cell transplantations. Up to 30% of patients with AML harbor an activating mutation in the FLT3 receptor tyrosine kinase (FLT3-ITD). Such mutations are associated with a high predisposition to relapse after remission. In a simplified way we can say that these tumor cells depend on FLT3: Is FLT3 blocked, cells die. Hence, FLT3 inhibitors are being developed as targeted therapy for FLT3-mutant AML; however, clinical responses are short-lived and their use is complicated by rapid development of resistance. This emphasizes the need for additional therapeutic targets.

Our study represents a novel therapeutic window to specifically target and kill AML cells with FLT3-ITD mutations. We found that the tumor-promoting enzyme CDK6 but not its close relative CDK4 directly regulates and initiates the production/transcription of FLT3 and thus lead to disease. The FDA-approved kinase inhibitor Palbociclib not only blocks the activity of CDK6 but in turn impairs FLT3 expression: Mutant AML cells die immediately. The treatment does not affect cells without the mutation.

The power of CDK6 inhibition in AML cells goes beyond FLT3: Palbociclib also stops production of the PIM1 kinase and thus overcomes the potential activation of survival pathways counteracting the effects of FLT3 inhibition.

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Women May Overestimate Breast Cancer Risk, Underestimate Obesity, Heart Disease Risks

MedicalResearch.com Interview with:

Julie M. Kapp, MPH, PhD Associate Professor 2014 Baldrige Executive Fellow University of Missouri School of Medicine Department of Health Management and Informatics Columbia, MO 65212

Dr. Kapp

Julie M. Kapp, MPH, PhD
Associate Professor
2014 Baldrige Executive Fellow
University of Missouri School of Medicine
Department of Health Management and Informatics
Columbia, MO 65212

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

Dr. Kapp: For the past several decades the U.S. has had the highest obesity rate compared to high-income peer countries, and for many years people in the U.S. have had a shorter life expectancy. For female life expectancy at birth, the U.S. ranked second to last. At the same time, the U.S. has the third highest rate of mammography screening among peer countries, and the pink ribbon is one of the most widely recognized symbols in the U.S. While the death rate in females for coronary heart disease is significantly higher than that for breast cancer, at 1 in 7.2 deaths compared to 1 in 30, respectively, women have higher levels of worry for getting breast cancer.

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Teenagers Who Eat Lots of Fruits & Vegetables May Lower Breast Cancer Risk

Dr. Maryam S. Farvid, PhD Takemi Fellow Harvard T.H. Chan School of Public Health

Dr. Maryam Farvid

MedicalResearch.com Interview with:
Maryam Farvid, Ph.D.
Visiting Scientist
Department of Global Health and Population
Harvard T.H. Chan School of Public Health

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

Dr. Farvid: Breast cancer is one of the most frequently diagnosed cancers and is the second leading cause of cancer deaths among women in the United States. While we know many breast cancer risk factors, few of them are easily modified. Further, evidence suggests that exposure to carcinogens and anti-carcinogens in early life may play an important role. According to this study, what women eat as teens or young adults could affect their breast cancer risk in the future. Teenage girls who eat a lot of fruits may have a lower risk of breast cancer later in life. The risk of breast cancer among women who reported the highest amount of dietary fruits during high school, about 2.9 servings of fruit a day, was 25 percent lower, compared with those who had eaten the lowest amount, about 0.5 serving of fruit a day. We also analyzed individual fruit and vegetable intake and risk of breast cancer: greater consumption of apple, banana, and grapes during adolescence, as well as oranges and kale for young adult was significantly associated with a reduced risk.

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Intra-operative Radiation For Breast Cancer Better For Patients and Environment

MedicalResearch.com Interview with:
Jayant S Vaidya MBBS MS DNB FRCS PhD  Professor of Surgery and Oncology,  Scientific Director, Clinical Trials Group, Division of Surgery and Interventional Science, University College London Whittington Health - Clinical Lead for Breast Cancer Royal Free Hospital University College London Hospital
Jayant S Vaidya MBBS MS DNB FRCS PhD 
Professor of Surgery and Oncology,
Scientific Director, Clinical Trials Group,
Division of Surgery and Interventional Science,
University College London
Whittington Health – Clinical Lead for Breast Cancer
Royal Free Hospital
University College London Hospital

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

Prof. Vaidya: TARGIT-A randomised clinical trial (ISRCTN34086741) compared giving TARGIT IORT during lumpectomy vs. traditional EBRT given over several weeks after lumpectomy for breast cancer; local-recurrence-free-survival was similar in the two arms of the trial, particularly when TARGIT was given simultaneously with lumpectomy. Also, there were significantly fewer deaths from other causes with TARGIT IORT.

This study calculated journeys made by patients with breast cancer to receive their radiotherapy, using the geographic and treatment data from a large randomised trial.

The study then assessed the same outcomes (travel distances, travel time and CO2emissions) in two semi-rural breast cancers—the results of this assessment confirm and reinforce the original results: the benefit of the use of TARGIT for patients from two semi=rural breast centres was even larger (753 miles (1212 km), 30 h, 215 kg CO2 per patient).

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Overdiagnosis of Breast Cancer Through Mammograms Complicated by Lack of Understanding of Tumor Progression

MedicalResearch.com Interview with:
Ragnhild Falk PhD
Oslo Centre for Biostatistics and Epidemiology
Research Support Services
Oslo University Hospital and
Solveig Hofvind PhD
Department of Screening Cancer Registry of Norway
and Oslo and Akershus University College of Applied Sciences
Oslo, Norway

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

Response: The issue of overdiagnosis has been heavily debated, and a variety of results have been presented. However, the exact proportion of overdiagnosis is unknown as one do not know what would have happen in the absent of screening.

We have split the proportion of overdiagnosis into two parts based on the time at which the death occur; scenario 1 as the proportion of women diagnosed with a screen-detected breast cancer and who died within the lead-time period, and scenario 2 as women detected with slow growing tumors that never would have caused any harm during the women’s life if she had not attended screening.

In principle, all screening programs will detect breast cancer among women who die of other causes in the near future since there exist competing risk of death among women targeted by screening. Although the all-cause mortality rates are low, it is inevitable.

We wanted to focus on the first scenario and estimated the number of women diagnosed with screen detected breast cancer who died within the estimated lead-time period caused by screening. We estimated his proportion to be less than 4 percent of all screen-detected cases in the given England & Wales and the Norwegian setting.

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Aromatase Inhibitors Do Not Increase Risk of the Most Fatal Cardiovascular Events in Breast Cancer Patients

MedicalResearch.com Interview with:

Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif

Dr. Reina Haque

Reina Haque, PhD MPH
Research scientist
Kaiser Permanente Southern California Department of Research & Evaluation

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

Dr. Haque: The study fills an important knowledge gap about the long-term association of aromatase inhibitors on cardiovascular disease risk in breast cancer survivors.

This was a retrospective cohort study that included a cohort of 13,273 postmenopausal breast cancer survivors who were diagnosed with breast cancer, either estrogen or progesterone receptor positive, from 1991 to 2010. The patients were followed through 2011, or a maximum of 21 years. The study participants were divided into four groups based on the drugs they received: 31.7 percent were treated only with tamoxifen; 28.6 percent only with aromatase inhibitors; 20.2 percent used both; and 19.4 percent did not use any of these drugs. These oral drugs are used to combat breast cancer recurrence, but may have long-term side effects on other organs.

The study determined that the risk of cardiac ischemia (which can lead to a heart attack) and stroke were not elevated in patients who only took aromatase inhibitors compared to those who only took tamoxifen. These results provide reassurance that aromatase inhibitors may not increase risk of the potentially fatal cardiovascular outcomes compared to tamoxifen.

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Most Patients Referred By Genetic Screening For Breast MRI Do Not Have Study Performed

MedicalResearch.com Interview with:

Stamatia Destounis, MD, FSBI, FACR Elizabeth Wende Breast Care, LLC, Clinical Professor of Imaging Sciences University of Rochester School of Medicine and Dentistry  Rochester NY 14620

Dr. Stamatia Destounis

Stamatia Destounis, MD, FSBI, FACR
Elizabeth Wende Breast Care, LLC,
Clinical Professor of Imaging Sciences
University of Rochester
School of Medicine and Dentistry
 Rochester NY 14620 

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

Dr. Destounis: Identification of women who have an increased risk of breast cancer is important, as they are often eligible for additional screening methods, such as breast MRI. One criterion for eligibility for screening breast MRI is >20% lifetime risk of breast cancer, as determined by risk assessment models through genetic counseling.

At my facility, we have incorporated a genetics program. Through the program we are flagging and identifying a large volume of patients who are potentially eligible for additional services. This study was conducted to determine the value of screening MRI in the patient subgroup who have undergone genetic counseling at my facility. In this group we found 50% of patients who were referred for counseling were also recommended to have screening MRI. However, only 21.3% of those recommended actually pursued the exam. Of those patients who did have a screening MRI, 4 were diagnosed with breast cancer, all of which were invasive and node negative. We ultimately had a 10% biopsy rate and 50% cancer detection rate in this subgroup.
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Tomosynthesis is Mammography Made Better

MedicalResearch.com Interview with:

Elizabeth A. Rafferty, MD Department of Radiology, Massachusetts General Hospital, Boston  Now with L&M Radiology, West Acton,  Massachusetts

Dr. Elizabeth Rafferty

Elizabeth A. Rafferty, MD
Department of Radiology,
Massachusetts General Hospital, Boston
Now with L&M Radiology, West Acton,
Massachusetts

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

Dr. Rafferty: Breast tomosynthesis has been approved for mammographic screening in the United States for just over 5 years, and many single center studies have demonstrated its improved performance for screening outcomes over digital mammography alone. Our previously published multi-center analysis, (JAMA 2014;311(24), the largest study on this topic to date, demonstrated significantly improved cancer detection and reduced recall rates for women undergoing tomosynthesis compared with digital mammography alone.  In the current issue of JAMA we evaluate the differential screening performance after implementation of breast tomosynthesis as a function of breast density.

While tomosynthesis continues to be increasingly available, questions remained about which women should be imaged with this technique. In particular, does this technology offer additional benefit for all women, or only for women with dense breasts. The size of the database compiled by the centers participating in this study allowed us to evaluate this important question.

The most critical finding of our study was that the use of tomosynthesis for breast cancer screening significantly improved invasive cancer detection rates while simultaneously significantly reducing recall rates both for women with dense and non-dense breast tissue. Having said that, the magnitude of the benefit was largest for women with heterogeneously dense breast tissue; for this population, tomosynthesis increased the detection of invasive cancers by 50% while simultaneously reducing the recall rate by 14%.

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New Drug Combination May Delay Brain Metastases in HER2+ Breast Cancer

MedicalResearch.com Interview with:

Ahmad Awada, MD, PhD Medical Oncology Clinic Institut Jules Bordet Université Libre de Bruxelles Bruxelles, Belgium

Dr. Ahmad Awada

Ahmad Awada, MD, PhD
Medical Oncology Clinic
Institut Jules Bordet
Université Libre de Bruxelles
Bruxelles, Belgium

MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. AwadaThis Study compared, in a randomized fashion, paclitaxel + trastuzumab to paclitaxel + neratinib in the first line setting of metastatic breast cancer. All outcome endpoints (PFS, OS, ORR) were similar.

In addition, paclitaxel + neratinib delayed the appearance and decreased the incidence of central nervous system (CNS) events (secondary end point)

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Awada:  Paclitaxel + neratinib is as effective as paclitaxel + trastuzumab.

The data suggested that neratinib could influence the pattern of CNS events in HER2+ metastatic breast cancer. These emerging data on CNS events are under validation in the NALA trial.

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Genetic Variants May Raise Risk of Breast Cancer In Pediatric Radiation Therapy Patients

MedicalResearch.com Interview with:

Lindsay M. Morton, PhD Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic National Cancer Institute Bethesda, Maryland

Dr. Lindsay Morton

Lindsay M. Morton, PhD
Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic
National Cancer Institute
Bethesda, Maryland

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

Dr. Morton: We know that childhood cancer survivors, particularly those who received radiotherapy to the chest, have strongly increased risk of developing breast cancer. We studied about 3,000 female survivors of childhood cancer to identify whether inherited genetic susceptibility may influence which survivors go on to develop breast cancer.

MedicalResearch.com: What are the main findings?

Dr. Morton: In this discovery study, we found that specific variants in two regions of the genome were associated with increased risk of breast cancer after childhood cancer among survivors who received 10 or more gray of chest radiotherapy. A variant at position q41 on chromosome 1 was associated with nearly two-fold increased risk and one at position q23 on chromosome 11 was associated with a more than three-fold increased risk for each copy of the risk alleles. However, the variant alleles didn’t appear to have an effect among survivors who did not receive chest radiotherapy.

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Biomarker Defines Subgroup of HER2-positive Breast Cancers Resistant to Herceptin

MedicalResearch.com Interview with:
Sherene Loi, MBBS(Hons), FRACP, PhD
Associate Professor, University of Melbourne
Consultant Medical Oncologist, Breast Unit
Head, Translatonal Breast Cancer Genomics and Therapeutics Lab
Cancer Council Victoria John Colebatch Fellow
Peter MacCallum Cancer Centre, East Melbourne
Victoria, Australia

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

Dr. Loi: Even though HER2 amplification/overexpression is such a strong oncogenic driver in breast cancer, clinical and biological heterogeneity is still evident. Our study was performed to investigate the hypothesis that a subgroup of patients with ER-positive, HER2-positive primary breast cancers seem to have lower responses to anti-HER2 therapy, in this case trastuzumab (trade name Herceptin), and we could better identify this group using both ER and HER2 levels. Our study was designed to try to better define this group so we could potentially evaluate the efficacy of future treatment strategies in this group, particularly as combination anti-HER2 therapy (i.e. trastuzumab and pertuzumab) is currently being investigated in the adjuvant setting.

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Infertility and Fertility Treatments Linked To Greater Breast Density

MedicalResearch.com Interview with:

Frida Lundberg | PhD Student Dept. of Medical Epidemiology and Biostatistics Karolinska Institutet

Frida Lundberg

Frida Lundberg | PhD Student
Dept. of Medical Epidemiology and Biostatistics
Karolinska Institutet

Medical Research: What is the background for this study?

Response: Fertility treatments involve stimulation with potent hormonal drugs that increase the amount of the sex hormones estrogen and progesterone. These hormones have been linked to breast cancer risk. Further, as these treatments are relatively new, most women who have gone through them are still below the age at which breast cancer is usually diagnosed. Therefore we wanted to investigate if infertility and fertility treatments influences mammographic breast density, a strong marker for breast cancer risk that is also hormone-responsive.

Medical Research: What are the main findings?

Response: We found that women with a history of infertility had higher absolute dense volume than other women. Among the infertile women, those who had gone through controlled ovarian stimulation (COS) had the highest absolute dense volume. The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased risk of breast cancer. However, the observed difference in dense volume was relatively small and has only been linked to a modest increase in breast cancer risk in previous studies.  As the infertility type could influence what treatment the couples undergo, the association might also be due to the underlying infertility rather than the treatment per se.

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Acupuncture May Improved Hot Flashes in Breast Cancer Patients

MedicalResearch.com Interview with:
Giorgia Razzini, PhD

Unit of Medical Oncology Civil Hospital
Carpi Italy;

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

Dr. Razzini: Hot flashes experienced by breast cancer patients is a significant clinical problem because there are few reliable treatment that are free of side effects and it sometime reduces compliance with endocrine therapy for prevention of cancer recurrence. Menopausal symtoms overall  heavily impact on quality of life..

Acclimat found that acupuncture combined with self-care for 3 months, is associated with significantly lower hot flash scores, compared to self-care alone ( advices on diet, physical exercise and psycoloigical support if needed).

Beneficial effects persisted up to 6 months follow-up. These effects were not associated with significant adverse events.

MedicalResearch.com: What should clinicians and patients take away from your report? 

Dr. Razzini:  Research suggests that breast cancer women do not receive adequate care for menopausal symptoms in the clinical practice of most oncology department. Our study showed that oncologists can offer them specific integrative management strategy for menopausal symptoms including acupuncture and enhanced self-care to women with breast cancer, particularly in younger women when treatment with hormonal treatment is recommended, in order to help women to stay on their therapy and improve their quality of life.
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