"Scientists have identified the first genetic variant specifically associated with the risk of a difficult-to-diagnose cancer sub-type accounting for around 10-15 per cent of all breast cancer cases.
The largest ever study of the breast cancer sub-type, called invasive lobular carcinoma, gives researchers important clues to the genetic causes of this particular kind of breast cancer, which can be missed through screening.
The research, published today in the journal PloS Genetics, was co-led by The Institute of Cancer Research, London, King’s College London, and Queen Mary University of London. It used gene chip technology and complex statistical analysis to compare the DNA of more than 6,500 women with invasive lobular cancer with the DNA of more than 35,000 women without the disease.
The study involved more than 100 research institutions from around the world and was funded by several organisations in the UK including Breast Cancer Campaign, Cancer Research UK, Breakthrough Breast Cancer and the ICR.
A woman with the genetic variant, called rs11977670, was found to have a 13 per cent higher chance of developing invasive lobular cancer than a woman without it. The variant is close to two genes on chromosome 7: BRAF, a known cancer-causing gene, and JHDM1D, which is involved in the activation and deactivation of other genes.
The discovery of the genetic variant, in conjunction with other markers, could help in the development of future genetic screening tools to assess women’s risk of developing invasive lobular cancer, and also gives researchers important new clues about the genetic causes of the disease and a related precursor to cancer called lobular carcinoma in situ.
Invasive lobular carcinoma develops in the lobes of the breast that produce milk and can be particularly difficult to diagnose, because the cancer often does not form a definite lump and may not show up on mammograms. As a result, women with this type of cancer tend to be diagnosed when the cancer is more advanced and more difficult to treat."
"A breast cancer therapy that blocks estrogen synthesis to activate cancer-killing genes sometimes loses its effectiveness because the cancer takes over epigenetic mechanisms, including permanent DNA modifications in the patient's tumor, once again allowing tumor growth, according to researchers.
The findings of this international team, headed by the University of Pittsburgh Cancer Institute (UPCI) in Pennsylvania, warrants research into adding drugs that could prevent the cancer from hijacking patients' repressive gene regulatory machinery, which might allow the original therapy to work long enough to eradicate the tumor. The study was published in Science Translational Medicine (2014; doi:10.1126/scitranslmed.3008326).
"Our discovery is particularly notable as we enter the era of personalized medicine," said senior author Steffi Oesterreich, PhD, of UPCI. "Resistance to hormonal therapy is a major clinical problem in the treatment of most breast cancers. Through testing of a tumor's genetic and epigenetic make-up, we may be able to identify the patients most likely to develop such resistance and, in the future, create a treatment regimen tailored to giving each patient the best chance of beating their cancer."
Epigenetic translates to above genetic and is an emerging field of study that looks at how environmental factors such as infections, pollutants, stress, and in this case, long-term exposure to drugs that block estrogen synthesis, could influence a person's DNA. Epigenetic changes do not alter the structure of the DNA, but they do change the way the DNA is modified, which subsequently determines the potential of gene regulation."
"A majority of cancer patients experience some level of fatigue during their course of treatment, and approximately 30% contend with persistent fatigue for years after treatment. Fatigue is among the most common and distressing long-term effects of cancer treatment and significantly affects patient quality of life. ASCO has adapted a pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Guideline for Cancer-Related Fatigue, and the NCCN Guidelines for Survivorship for use in the screening, assessment, and management of fatigue in adult survivors of cancer.
The adapted guideline, reported in the Journal of Clinical Oncology by Bower et al, applies to cancer survivors diagnosed at age ≥ 18 years who have completed primary cancer treatment with curative intent and are in clinical remission off therapy and to patients who are disease-free and have gone on to maintenance or adjuvant therapy. The guideline targets health-care professionals including medical, surgical, and radiation oncologists, psychosocial and rehabilitation professionals, primary care providers, nurses, and others involved in care for survivors, as well as patients, family members, and caregivers of patients who have survived cancer.
The primary guideline question was: “What are the screening, assessment, and treatment approaches to the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment?” A summary of the adapted guideline recommendations follows."
Susan Zager's insight:
All health-care providers should routinely screen patients for the presence of fatigue from diagnosis onward, including after completion of primary treatment, at least annually and as clinically indicated.
Elements of care include education and counseling, resolution of contributing factors, physical activity programs, psychosocial interventions, mind-body interventions, and pharmacologic interventions.
"Most breast cancers are treated by blocking their addictions, for example depriving estrogen-fueled tumors of estrogen. But what about breast cancers without these hormonal addictions? In so-called "triple negative" tumors the cancer's addiction remains a mystery, making this subtype difficult to treat. However, a University of Colorado Cancer Center study presented today at the American Association for Cancer Research (AACR) Annual Meeting 2014 showcased a new drug active against triple-negative breast cancer, and through analysis of the drug's mechanism of action, offers increased understanding of the biology of this very aggressive form of breast cancer.
"We developed the compound AMPI-109 in collaboration with Dr. Rahul Ray, a synthetic organic chemist at the Boston University School of Medicine, and showed its effectiveness in preliminary studies of renal and prostate cancers. But it seemed initially as if the drug was inactive against breast cancer," says James R. Lambert, PhD, investigator at the CU Cancer Center and assistant research professor at the CU School of Medicine.
However, the initial test of AMPI-109 had been performed against only one form of breast cancer and this disease is notoriously heterogeneous. Despite initial negative results, the group decided to investigate the drug's efficacy against a panel of all known breast cancer subtypes. Strikingly, Lambert and colleagues found the drug was especially effective in specifically one subtype: triple-negative breast cancer, in which the drug blocked the growth of cells by greater than 50 percent.
"This was exciting," Lambert says, "not only did we have a drug that potentially targeted triple-negative breast cancer, but we had a biochemical tool that could be used to dissect the molecular underpinnings of the disease. "
To begin to investigate the molecular mechanism of AMPI-109 action in triple negative breast cancer, the group performed a genome-wide functional genetic screen, individually turning off every gene in the cell while exposing the cells to the drug. Identification of the silenced genes in cells that survived drug treatment would show which genes are essential for the drug's cell-killing effect.
"A few weeks ago, I mentioned that there would be an exciting announcement made this week at the American Association of Cancer Research (AACR) annual meeting held this year in San Diego.
Both Pfizer and Eli Lilly have released their reports on the successful trial findings using CDK 4/6 inhibitor drugs.
Pfizer's drug is palbociclib and Eli Lilly's drug is bemaciclib. Both have been used for post-menopausal women who have metastatic estrogen receptor positive (ER+) breast cancer. Although breast cancer has several subtypes, ER+ is the largest population, with approximately 50,000 American women in this category.
What have they shown with this drug? They have shown that a cancer tumor can be targeted without killing the good cells at the same time, which is what chemotherapy does. That is why chemo has such horrible side effects. I think by now we all know what those side effects are, since I have experienced them all and am living with many that will always be with me.
The idea of creating "targeted therapy" is something that the Noreen Fraser Foundation has funded at UCLA from the beginning. We believed in this research and, of course, in the brilliance of both Dr. Dennis Slamon and Dr. Richard Finn, who were the principal investigators. About two years ago, Pfizer took over the research from UCLA and committed $190 million to continue the development."
Susan Zager's insight:
This is so encouraging to see that research is paying off and Noreen Frasier who has metastatic breast cancer is able to get this new treatment that doesn't come with heavy side effects. Pfizer's drug is called palbociclib and Eli Lilly's drug is called bemaciclib. Both are used for ER+ post-menopausal women and are CFK 4/6 inhibitors. With these drugs they have demonstrated that a cancer tumor can be targeted without killing the good cells at the same time, which helps by not having traditional chemotherapy side effects. They are making Noreen tired but keeping her tumors at bay and this kind of research is very exciting. According to Noreen, "Today, life is good and things are looking up!"
Noreen Fraser is living with Stage IV metastatic breast cancer. She is the Founder and CEO of the Noreen Fraser Foundation, a 501(c)(3) non-profit organization dedicated to funding groundbreaking women's cancer research.
Donald A. Berry, PhD, is a leader in the development of innovative statistical methodology for the improvement of clinical trial design and analysis, especially the Bayesian methods used in the I-SPY program.
Can you describe your involvement in the I-SPY trials and why these trials are so important?
I designed I-SPY 1 and I-SPY 2, working in developing and running I-SPY 2 with many others, especially Laura J. Esserman, MD, MBA, Anna D. Barker, PhD, and Janet Woodcock, MD. Traditional trials address a single question and progress is slow, while I-SPY 2 asks many questions, and answers them in an efficient, accurate way. Traditional trials are fixed and rigid, while I-SPY 2 is flexible and adaptive. The goal and the effect is to greatly decrease the overall duration of drug development. Both aspects are essential for accelerating progress in cancer. In addition, I-SPY 2 uses information garnered in the trial to treat trial participants more effectively.
I-SPY 2 introduced many innovations into the modern era of clinical trials and drug development, including:
Experimental agents evaluated for efficacy first in early “curable” disease
Many pharma companies contributing experimental drugs in an implicitly competitive trial, to everyone’s benefit
Learning during the trial which experimental regimens benefit which biomarker subsets
Adaptive randomization: patients with tumors that respond better to an experimental agents get assigned to that agent with higher probability. There are two important consequences: (1) patients in the trial receive treatments better for them and (2) agents that are performing well in particular subsets move through the process and “graduate” more rapidly
Regimens enter and leave the trial
Screening all patients for markers
Phase II trial but driven by a registration endpoint
Longitudinal modeling of patient outcomes (MRIs are given early to help understand the course of the patient’s disease and relate early assessments to the longer-term primary endpoint of the trial)
Adaptive sample size (veliparib graduated with 62 patients having been assigned and neratinib graduated having been assigned to 115 patients)
Graduations and futility dropping are based on predicting future success in a subsequent phase III trial
"(HealthDay News) -- Racial and ethnic minority patients seem to be more vulnerable to breast cancer-related privations and financial decline, according to a study published online March 24 in the Journal of Clinical Oncology.
Reshma Jagsi, M.D., from the University of Michigan in Ann Arbor, and colleagues examined the financial experiences of a racially and ethnically diverse cohort of women diagnosed with nonmetastatic breast cancer from 2005 to 2007. Surveys were conducted about nine months after diagnosis and four years later among 1,502 women.
The researchers found that the median out-of-pocket expenses were ≤$2,000, with 17 percent reporting spending >$5,000. At four years after diagnosis, 12 percent of respondents reported medical debt, with significant variation by race: 9 percent for whites; 15 percent for blacks; 17 percent for English-speaking Latinas; and 10 percent for Spanish-speaking Latinas (P = 0.03). One-quarter of women experienced financial decline that was at least partly due to breast cancer, with increased odds of decline for Spanish-speaking Latinas versus whites (odds ratio [OR], 2.76; P = 0.006). Eighteen percent of the sample reported at least one privation, with privation significantly more likely for blacks (OR, 2.6; P < 0.001) and English-speaking Latinas (OR, 2.2; P = 0.02) versus whites.
"Racial and ethnic minority patients appear most vulnerable to privations and financial decline attributable to breast cancer, even after adjustment for income, education, and employment," the authors write."
"The CDK4/6 inhibitor LY2835219 demonstrated promising single-agent activity in heavily pretreated patients with hormone receptor (HR)-positive metastatic breast cancer, according to a phase I expansion cohort analysis presented at the 2014 AACR Annual Meeting. The phase I study evaluated LY2835219 in 132 patients with glioblastoma, melanoma, lung cancer, colorectal cancer, and breast cancer. The study specifically enrolled 47 heavily pretreated patients with metastatic breast cancer, 36 of which were HR-positive. In these patients, the median progression-free survival (PFS) was 9.1 months, the overall response rate (ORR) was 25%, and the meaningful clinical benefit rate (CBR) was 61%. “Although our study was not designed to compare patient outcomes based on HR status, the clinical benefit rate was 61% in our patients with HR-positive breast cancer, which means patients had disease control for longer than 24 weeks or had their tumors reduce in size by more than 30%,” said the study’s lead author Amita Patnaik, MD, an associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas. In the study, LY2835219 was administered continuously at doses ranging from 150 mg to 200 mg every 12 hours in a 28-day cycle. In the breast cancer cohort, patients had received a median of 7 prior systemic therapies. In the 36 patients with HR-positive breast cancer, 9 achieved a partial response (PR) with no complete responses for an ORR of 25%. Altogether, 20 patients (56%) had stable disease (SD), 13 of which lasted ≥ 24 weeks. The overall CBR was 81% and was 61% specifically in patients who experienced longer durations of SD. The PFS was 9.1 months for patients with HR-positive breast cancer with 50% of patients remaining on LY2835219 therapy at the time of the analysis. Across all 47 patients with breast cancer, 9 (19%) achieved a PR and 24 (51%) had SD for a CBR of 70%. The median PFS was 5.8 months. The most common grade 3/4 treatment-related adverse events across the full study (n=132) were neutropenia (11%), diarrhea (5%), nausea (3%), fatigue (2%), and vomiting (2%). “This is very encouraging, and warrants the initiation of future clinical trials in this setting where treatments are needed,” said Patnaik. “When tested on various breast cancer types in preclinical studies, HR-positive cells were found to be highly sensitive to this drug. Approximately 80% of breast cancers are HR-positive.” Blocking CDK 4 and 6 acts on the cell cycle by stopping DNA synthesis through the prevention of progression from G1 to S phase. Preclinical models have demonstrated preferential activity for these agents in HR-positive breast cancer, resulting in a number of agents being investigated in early and late stage trials."
SAN DIEGO — The new oral drug LY2835219, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, showed early promise as monotherapy for patients with metastatic breast cancer, particularly for those with hormone receptor (HR)-positive disease, according to results of a phase I study presented here at the AACR Annual Meeting 2014, April 5-9.“Preclinical evaluation indicated that LY2835219 may have a potential therapeutic application for the treatment of human cancers in which aberrant CDK-4/6 pathway enhances cancer cell growth,” said Amita Patnaik, M.D., associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas. “When tested on various breast cancer types in preclinical studies, HR-positive cells were found to be highly sensitive to this drug.“Approximately 80 percent of breast cancers are HR-positive,” added Patnaik. “Although our study was not designed to compare patient outcomes based on HR status, the clinical benefit rate was 61 percent in our patients with HR-positive breast cancer, which means patients had disease control for longer than 24 weeks or had their tumors reduce in size by more than 30 percent. This is very encouraging, and warrants the initiation of future clinical trials in this setting where treatments are needed.”In this phase I trial, Patnaik and colleagues tested LY2835219 as a single-agent treatment for five different types of tumors."
"The 105th Annual Meeting of the American Association for Cancer Research will be held April 5-9, 2014, in San Diego, California. With about 18,000 researchers, patient advocates, and other professionals in the cancer field from around the world scheduled to be in attendance, the 2014 Annual Meeting continues the tradition of being the premier cancer research event where the latest and most exciting basic, translational, and clinical discoveries are presented. It provides a unique opportunity for members of the worldwide cancer research community to learn about cutting-edge advances, obtain feedback on their own research, and make connections that will foster future collaborations.
The theme for this year’s meeting, “Harnessing Breakthroughs – Targeting Cures,” reflects the fact that the translation of basic science into clinical advances for the benefit of cancer patients is occurring at an increasing pace and more seamlessly than ever before. Along with hundreds of invited talks from an elite roster of speakers, we will feature more than 6,000 proffered papers from the world’s top cancer researchers. As a new feature of this year’s meeting, we are providing five early-career investigators, called “NextGen Stars,” the chance to present their research during selected major symposia and current concepts sessions. We are very excited about this initiative because it is vital that we acknowledge the great work of these young investigators who will drive the remarkable progress against cancer going forward.
The annual meeting will also showcase pioneering clinical trials, many of which will highlight emerging approaches for personalizing cancer care. The therapeutics being evaluated in these clinical trials are underpinned by our knowledge of cancer biology, and this meeting provides a tremendous opportunity for basic and clinical researchers and clinicians to exchange ideas. Recognizing that personalized cancer medicine requires multidisciplinary and multi-institutional collaboration, we are also offering a robust regulatory science and policy track with 10 exciting sessions that will be of significant interest to both laboratory and clinical scientists in all subfields and sectors of the cancer field.
Susan Zager's insight:
Annual Meeting of the AACR will be held April 5-9, 2014, in San Diego, California
"Breast cancer patients with negative sentinel lymph node (SLN) biopsies can skip axillary lymph node dissection (ALND), according to an updated clinical guideline from the American Society of Clinical Oncology.
The same advice applies to most women who have one or two SLN metastases and plan to have breast-conserving surgery and whole-breast radiation therapy. Patients who have SLN metastases and opt for mastectomy should be offered axillary lymph node dissection, according to an article published online in the Journal of Clinical Oncology.
The update represents a major departure from the original version of the guideline, which recommended axillary lymph node dissection for all women with SLN involvement.
The change came about as a result of "recent trials that suggest no difference in outcomes and fewer complications with sentinel-node biopsy alone," guideline panel chair Gary Lyman, MD, of the Fred Hutchinson Cancer Research Center in Seattle, told MedPage Today via email.
"A new UCLA study on cell metabolism could lead to treatments for viral infections as well as cancer. A research team led by Minh Thai, a post-doctoral scholar, and Heather Christofk, an assistant professor of molecular and medical pharmacology, published their findings online on April 1 in the journal Cell Metabolism.
The study authors note that their study is the first to explain how viruses reprogram the cells they invade to promote their continued growth within an organism. They explain that their findings could have implications in cancer treatments based the on similarities between viruses and cancer cell mechanisms; thus, they could possibly lead to the development of drugs that could inhibit viruses, such as the one that causes the common cold.
The investigators note that a cell’s metabolism basically entails processes that go on within the cell, which are a group of physical and chemical events that feed and maintain the cell, allow it to reproduce, and eventually decide when it will die off and be replaced by its daughter cells. When a virus infects a cell, it initiates changes in the cell’s metabolism; thus, reprogramming the cell in such a manner that it stimulates maintenance and reproduction of the virus. It is known that viruses reprogram cells; however, the molecular mechanisms that a virus uses to accomplish this were previously unknown."
"Breast Cancer Wellness Magazine released the digital version of its Spring, 2014 issue on Wednesday, March 26, 2014 that features Mrs. Lori Baran’s article, Moving Beyond Hope in the Inspire section. Lori describes herself as a 'Stage IV metastatic breast cancer survivor.' In the article, as she shares her breast cancer journey, she is demonstrating how she is a thriver, Moving Beyond Hope.
Lori is involved in many breast cancer advocacy issues, organizations and projects. This author is always excited to find people of like minds who have embraced Complementary and Alternative Medicine (CAM) modalities, especially the Young Living Essential Oils (YLEO) Clinical Aromatherapy lifestyle. Lori has both embraced Clinical Aromatherapy and is affiliated with YLEO. However, the most important aspect is that she is restoring and supporting her body and continues to get good reports from her doctors. You can learn more about Lori's journey through her book, After Cancer by Lori . (You can learn more about Clinical Aromatherapy and the cancer population in the articles recommended below.)
The Breast Cancer Wellness Magazine brand is ‘BE A THRIVER!’ To this author, one aspect of being a Thriver is moving beyond day-to-day survival into progressive actions that are for the long-term benefit of everyone. ONE Health Institute, is the not-for-profit organization that serves Breast Cancer Wellness Magazine (BCWM); from the BCWM website: “The mission of Breast Cancer Wellness is to support the mental, emotional, physical, spiritual and environmental healing needs of women facing breast cancer, no matter what age or stage of the journey. ONE Health Institute and BCWM publishes the print and digital magazine, hosts an annual Thrivers Cruise, provides scholarships to attend and does much more to Grow, Nourish, Renew, Inspire and Connect, the breast cancer population to move from just surviving to thriving. Check it out!"
"ASCO has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer for use in the screening, assessment, and care of anxiety and depressive symptoms in adults with cancer. The adapted guideline, reported in the Journal of Clinical Oncologyby Andersen et al, applies to patients aged ≥ 18 years at any phase of the cancer continuum and regardless of cancer type, disease stage, or treatment modality, and is targeted to professional health-care providers including medical, surgical, and radiation oncologists, psychiatrists, psychologists, primary care providers, nurses, and others involved in care, as well as to patients, family members, and caregivers.
The pan-Canadian guideline underwent methodologic review by ASCO senior guideline staff members and content review by an ASCO ad hoc panel including multidisciplinary representation. The expert panel was cochaired by Barbara L. Andersen, PhD, of The Ohio State University, and Julia Howe Rowland, PhD, of the National Cancer Institute.
The final recommendations of the adapted guideline are as follows:
All patients with cancer and cancer survivors should be evaluated for symptoms of depression and anxiety periodically across the trajectory of care. Assessment should be performed using validated measures. Depending on levels of symptoms, different treatment pathways are recommended (see below). Failure to identify and treat anxiety and depression in cancer patients increases the risk of poor quality of life and, potentially, risk of disease-related morbidity and mortality.
Health-care practitioners implementing the guideline recommendations should first identify the available resources in their institution and community for the treatment of depressive and anxiety symptoms. The availability and accessibility of supportive care services are important in preventing or reducing the severity of symptoms of psychopathology.
Susan Zager's insight:
All patients with cancer and cancer survivors should be evaluated for symptoms of depression and anxiety periodically across the trajectory of care.
Adequate care requires supportive care services and ongoing follow-up and assessment.
"Women with aggressive breast cancer now have a new option for treatment.
Two years ago, doctors told Lisa Ridgeway she had triple negative breast cancer, a very aggressive disease with no cure. “There are not a lot of drugs that work, or work for a long period of time,” Ridgeway said.
The mother of two faced a typical life expectancy of just three years. “That’s a mom’s horror story, knowing that you aren’t going to be here,” she said.
Lisa had surgery, radiation, and chemo, but her cancer came back two more times. Now she’s trying something new. Doctors at the Cleveland Clinic are offering patients hyperthermia treatment.
“Hyperthermia is heat therapy. It’s actually been around since the time of the Egyptians,” Jennifer Yu, MD, Radiation Oncologist at Cleveland Clinic explained.
A hot bag is placed on top of the skin. A microwave unit heats the bag and the tissue under it to about 110 degrees. The heat increases blood flow and makes tumors more sensitive to radiation. “And it improves cell kill,” Dr. Yu said.
In one study, 66 percent of cancer patients who had hyperthermia and radiation had their tumors shrink completely compared to just 42 percent who had only radiation. Lisa hopes the treatment will give her more time. “My choice is I want to live,” she said.
Dr. Yu says about 10 centers around the country use hyperthermia for breast cancer. One of them is Temple University Medical Center in Philadelphia. Typically, treatments last one hour and are performed one to two times a week. Hyperthermia is also used in other cancers such as melanomas, gynecologic cancers, and head and neck cancers."
"Receptor status discordance, such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and metastatic lesions has been reported. The aim of this study was to evaluate the biopsy of clinically diagnosed metastatic lesions and to determine the changes in hormonal receptor and HER2 status of the metastatic lesions.
Methods: Sixty-three patients with clinically diagnosed metastatic breast cancer underwent an excisional biopsy or core needle aspiration guided by computed tomography/ultrasound.
ER, PR and HER2 were assessed by immunohistochemistry (IHC).
Results: A total of 48 metastases (76.2%) and nine second primary malignancies (14.3%, seven primary lung cancers and two primary pancreatic cancers) were found. The discrepancies between ER, PR and HER2 status between the primary breast cancer and metastatic lesions were 14.6%, 16.7% and 8.3%, respectively.
Six lesions (9.5%) were proved benign upon biopsy."
"SAN FRANCISCO, April 9, 2014 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR), a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technologies, today announced that preclinical data for NKTR-102 and NKTR-214 were presented at the 2014 Annual Meeting of the American Association of Cancer Research (AACR) being held in San Diego, California.
Positive preclinical data was presented for NKTR-102 (etirinotecan pegol), a novel, next-generation topoisomerase I inhibitor, which is currently in Phase 3 development for the treatment of advanced breast cancer. In a model of triple-negative breast cancer with brain metastases (MDA-MB-231Br cell line), NKTR-102 reduced the size and number of brain metastases and also prolonged survival as compared to both placebo and irinotecan, a first-generation topoisomerase-I inhibitor.
"Brain tumors resulting from metastatic breast cancer are notoriously difficult to treat because of the inability to achieve effective concentrations of standard anti-cancer agents in these tumors," said Paul R. Lockman, PhD., Chair of the Department of Basic Pharmaceutical Sciences, and the Associate Center Director for Translational Research in the Mary Babb Randolph Cancer Center. "These remarkable preclinical data for NKTR-102 clearly demonstrate that the drug's extended half-life combined with its unique molecular design allow NKTR-102 to penetrate through leaky brain tumor vasculature and concentrate in metastasized tumors, which results in significant tumor reduction and prolonged survival."
NKTR-102 is currently being evaluated in the BEACON study, which is a Phase 3, open-label, randomized, multicenter study of NKTR-102 that enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with ATC. More than one million women worldwide are diagnosed with breast cancer globally every year. (1) The chance of developing invasive breast cancer at some time in a woman's life is a little less than one in eight (12%). There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year. (2) Metastatic breast cancer refers to cancer that has spread from the breast to distant sites in the body.
Susan Zager's insight:
Abstract #4592: "Etirinotecan pegol accumulates in breast cancer brain metastases and prolongs survival in an experimental model of brain metastases of human triple negative breast cancer"
"Women whose breast cancer has spread to just a few axial lymph nodes are less likely to have their disease recur or to die from it if they have radiotherapy after mastectomy, according to new research. This study was presented at the European Breast Cancer Conference in Glasgow, Scotland, and was published in The Lancet (2014; doi:10.1016/S0140-6736(14)60488-8).
Until now, there has been uncertainty over whether women with early breast cancer that has spread to just one, two, or three lymph nodes under the arm gain any benefit from radiotherapy after surgery, explained Paul McGale, PhD, of the Early Breast Cancer Trialists' Collaborative Group at the Clinical Trial Services Unit in Oxford, United Kingdom.
"Another result from our study is that the proportional benefits of radiotherapy were similar in women regardless of whether or not they had also received chemotherapy or hormonal therapy. This is important because most women today receive these therapies. Our results suggest that women being treated today are likely to also benefit from radiotherapy if they have any positive lymph nodes," said McGale.
The research team analyzed results from 3,786 women in 14 randomized trials starting between 1964 and 1982. The women had underwent mastectomy along with the surgical removal of lymph nodes under the arm (axillary dissection) and were then randomized to either radiotherapy to the chest wall and surrounding regions or no radiotherapy. The women fell into three categories: those with no cancer in the lymph nodes; those with cancer in one, two, or three lymph nodes; and those with cancer in four or more lymph nodes. The women were followed for an average of a little more than 11 years, and data on the number of recurrences and deaths were available up to 2009."
"The combination of palbociclib and letrozole more than doubled progression-free survival (PFS) and showed a non–statistically significant 4.2-month improvement in overall survival (OS) for patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, according to results from the phase II PALOMA-1 trial that were presented at the 2014 AACR Annual Meeting. In the 165-patient open-label study, the CDK 4/6 inhibitor palbociclib improved PFS by 20.2 months compared with 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; P = .0004). The median OS was 37.5 months with palbociclib compared with 33.3 months with letrozole alone (HR = 0.813; 95% CI, 0.492-1.345; P = .2105). This first analysis of OS contained data from 61 patients (37%) and was not deemed statistically significant. A follow-up analysis of OS will be conducted once more events have accrued. “The palbociclib and letrozole combination demonstrated a significantly improved clinical outcome for patients who had hormone receptor-positive, metastatic breast cancer in this phase II trial,” said the study’s lead author Richard S. Finn, MD, an associate professor of medicine at the University of California, Los Angeles (UCLA). “The point of a randomized, phase II study is to have evidence that gives us confidence to do a phase III study, and we think that this study proved the hypothesis that a combination of palbociclib and letrozole is better than letrozole alone in this subgroup of patients.” Interim findings from the PALOMA-1 study culminated in a Breakthrough Therapy Designation from the FDA in April 2013. Pfizer, the company developing palbociclib, announced it is currently in discussions with the FDA to define the appropriate regulatory path forward for the drug."
"SUNDAY, April 6, 2014 (HealthDay News) -- In an early trial, an experimental breast cancer drug stopped disease growth and shrank tumors by more than 30 percent in some patients.
The pill, bemaciclib, was safe and well-tolerated by women with breast cancer that had spread, or metastasized, to other parts of the body, according to the results of this phase 1 trial.
"This is a novel oral treatment for patients with metastatic breast cancer," said lead researcher Dr. Amita Patnaik, the associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio.
If these results are replicated in future trials, it's conceivable that the pill might extend survival for women with terminal breast cancer, experts suggested.
The drug was particularly effective for the most common type of breast cancer, called hormone receptor-positive breast cancer. In this type of cancer, cancer cells grow in response to signals from the hormones estrogen and/or progesterone.
The study included more than 130 women. Overall, Patnaik said half of them had cancer growth controlled and 25 percent had shrinkage of their tumors.
Unlike standard cancer drugs, this is a twice-daily pill that allows women to go on with their daily lives. In contrast, other cancer drugs are given intravenously at a hospital or doctor's office. Another difference, Patnaik said, is that bemaciclib is a targeted therapy, a newer type of drug that is better able to identify and attack specific cells."
"PHILADELPHIA —Women who took clomiphene citrate (brand name Clomid) or gonadotropins as a part of fertility treatment did not experience an increased risk for breast cancer over 30 years of follow-up, compared with women who were not treated with these medications, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
"We wanted to evaluate the long-term relationship of fertility medications and breast cancer risk after controlling for other factors that have been shown to be correlated with both breast cancer risk and use of those drugs," said Louise A. Brinton, Ph.D., M.P.H., chief of the Hormonal and Reproductive Epidemiology Branch at the National Cancer Institute (NCI) in Bethesda, Md. "Overall, our data show that use of fertility drugs does not increase breast cancer risk in this population of women, which is reassuring."
An elevated risk for invasive breast cancer was observed for a small number of women who were exposed to 12 or more cycles of clomiphene, who had a little more than 1.5 times the risk of women in the study who never took fertility drugs. Women who were unable to become pregnant after taking gonadotropins and clomiphene citrate had nearly twice the risk of women in the study who never took either medication.
"The observed increase in risk for these small subsets of women may be related to persistent infertility rather than an effect of the medications," said Brinton. "Nevertheless, these findings stress the importance of continued monitoring of women who are exposed to fertility drugs."
Under current practices, clomiphene is usually limited to three to six cycles at doses up to 100 mg, which is far lower than in the past, including patients in this study who were prescribed doses up to 250 mg, oftentimes for many years, explained Brinton.
"By the time the elderly woman surrendered the 10 dogs living in her mobile home in rural Maryland, the shih tzus were unkempt and full of fleas and had gone years without their shots. A cream- and mushroom-colored female named Akyra, with a sweet disposition and a comical underbite, was in such bad shape that volunteer rescue groups declined to take her in.
Akyra’s mammary glands were riddled with tumors, including one the size of a golf ball. She would be hard to place in a home, and the medical care she needed would be expensive. The tumors could be cancerous.
“When my husband called and said they were going to leave one of the dogs behind because she had mammary tumors, I said, ‘No, you’re not!’ ” said Bekye Eckert, 49, a dog lover who lives outside Baltimore and has cared for several animals with mammary cancer.
Ms. Eckert arranged for Akyra to be enrolled in an innovative program at the University of Pennsylvania, where veterinary oncologists are learning about the progression of human breast cancer by treating mammary tumors in shelter dogs.
Like breast cancer in humans, tumors of the mammary glands are among the most common cancers in female dogs. Most pet owners never see this type of cancer because it is rare in animals that are spayed at a young age. Mammary cancer in dogs is fueled by estrogen, as it is in humans, so removing a dog’s ovaries greatly reduces the risk.
But among strays, females used as breeders in puppy mills and other unspayed female dogs, one in four has tumors.
Mammary cancers in dogs respond to many of the chemotherapy drugs that are used in people, and feature some of the same molecular abnormalities. As in humans, the risk of tumors increases with age, though some breeds, especially smaller dogs, develop the cancer at higher rates than others.
Because dogs typically have 10 mammary glands and often develop tumors in several glands at the same time, they present a unique research opportunity, enabling scientists to study lesions that are at different stages of development — from benign to cancerous, and at transitional stages — all in the same animal.
“The dog gives us the potential to answer the question: When did something go wrong at the molecular level?” said Dr. Karin Sorenmo, chief of medical oncology at Penn Vet’s Ryan Hospital, who founded the Penn Vet canine mammary tumor program in 2009. “We can also study the benign tumors and ask: What’s different in that one tumor that doesn’t change and become malignant versus another one that does change?”
Susan Zager's insight:
This is an interesting look at breast cancer in dogs and how it relates to humans.
MENLO PARK, CA and THE WOODLANDS, TX, Apr 02, 2014 (Marketwired via COMTEX) -- Corcept Therapeutics Incorporated CORT-4.51% , a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic, psychiatric and oncologic disorders, and US Oncology Research, one of the largest community-based research programs in the United States, announced today that two sites affiliated with US Oncology Research will participate in Corcept's multi-center, Phase I clinical study of mifepristone in combination with chemotherapy drug eribulin (Halaven(R))(1) in patients with metastatic or locally advanced unresectable breast cancer.
"Our research has focused primarily on metastatic triple-negative breast cancer, an aggressive form of cancer with a particularly poor prognosis. Currently, there is no FDA-approved treatment or standard chemotherapy regimen," said Joyce O'Shaughnessy, M.D., the US Oncology Research study lead and the Celebrating Women Chair of Breast Cancer Research at Texas Oncology - Baylor Charles A. Sammons Cancer Center. "We are pleased to be working with Corcept to investigate the potential that mifepristone may have in the treatment of this devastating disease."
Up to 20 patients with metastatic breast cancer will be eligible to enroll in the first phase of the study, which will determine the maximum tolerated dose of the mifepristone - eribulin combination. Up to an additional 20 patients with glucocorticoid receptor-positive metastatic triple-negative breast cancer will be enrolled into a subsequent expansion phase. This portion of the study will include efficacy endpoints.
The US Oncology Research participating sites include Texas Oncology - Baylor Charles A. Sammons Cancer Center, led by principal investigator Carlos Becerra, M.D. and Virginia Cancer Specialists, led by Alex Spira, M.D., PhD, F.A.C.P."
Hanna Sanoff MD, MPH Lineberger Comprehensive Cancer Center Department of Medicine University of North Carolina, Chapel Hill, NC
MedicalResearch.com: What are the main findings of the study?
Dr. Sanoff: We measured p16, a protein that increases with cellular aging, in blood cells of women receiving chemotherapy for breast cancer. We found that a standard course of chemotherapy led to an increase in p16 expression equivalent to what we have previous seen in people over the course of 10-15 years of chronological aging. This increase persisted in cancer survivors an average of three and half years after treatment.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Sanoff: The findings were in line with what we expected, though we were unsure how profound and persistent rise a rise in this molecular marker to expect.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Sanoff: Clinicians already are familiar with the idea that chemotherapy can cause long term adverse effects, effects that in some cancer survivors are profound. Our data raise the notion that accelerated molecular aging may underlie these problems. However, chemotherapy unequivocally saves lives. We think it premature to use our findings to make decisions about chemotherapy.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Sanoff: We are actively investigating how well the level of this marker, p16, can predict the actual experience of people during chemotherapy:
Are people with a high p16 (suggesting an advanced molecular age) more susceptible to chemotherapy effects?
Do people in whom chemotherapy leads to an elevated p16 manifest more weakness and difficulty with their physical function as we seen with advanced chronologic age?