"Dr. Lee Schwartzberg, Editor-in-Chief of PracticeUpdate Oncology, recommends the following papers in breast cancer to be presented at the ESMO 2014 Congress held September 27 through September 30, 2014, in Madrid.
September 27, 2014; 12:45 PM–1:45 PM
Poster Discussion: Metastatic and Locally Advanced Breast Cancer: Facing With Heterogeneity and Endpoints in Clinical Trials
358PD Vinflunine (VFL) plus capecitabine (CAPE) for advanced breast cancer (ABC) previously treated with or resistant to anthracycline and resistant to taxane : a phase 3 study versus capecitabine.
Authors: MM Jimenez, Y Demidchik, I Bondarenko, et al
This open-label, multicenter study randomized 770 ABC patients (up to three prior CT regimens) to VFL plus CAPE (n=384) or CAPE alone (n = 386). Patients taking VFL plus CAPE had prolonged PFS compared with CAPE alone (median, 5.6 vs 4.1 months; P = .0426). VFL plus CAPE had better response rate (22.9% vs 17.9%), disease control rate (57.3% vs 47.9%), and OS (674 total deaths; 13.9 months vs 11.7 months). The most frequent grade 3/4 event was neutropenia for the combination and hand–foot syndrome for CAPE.
For A/T pretreated/resistant patients with ABC, VFL plus CAPE showed significant improvement in PFS over CAPE alone.
359PD Final efficacy and safety analysis of the CARIN phase III trial: Capecitabine (Cap) and bevacizumab (Bev) with or without vinorelbine (Vin) in 1st line metastatic breast cancer (MBC).
Authors: A Welt, N Marschner, C Lerchenmüller, et al
"Advanced breast cancer (ABC) is a treatable but still generally incurable disease. The goals of care are to optimize both length and quality of life. Due to continuous research, several advances have been made, particularly for the human epidermal growth factor receptor 2 (HER-2)-positive and for luminal-like subtypes. Notwithstanding these advances, median overall survival of patients with ABC is still only 2–3 years, although the range is wide [1–5], and survival may be longer for patients treated in specialized institutions . Implementation of current knowledge is highly variable among countries and within each country.
The use of treatment guidelines has been associated with a significant improvement in survival [7–9]. This has been achieved mainly in early breast cancer. For ABC, and particularly metastatic breast cancer (MBC), less level 1 evidence exists and only recently has international consensus guidelines been developed (ABC1) . The ABC Consensus Conference was created by the European School of Oncology (ESO) with the ambitious goal of improving outcomes for all patients with ABC. Backed by strong political advocacy, ABC guidelines are seeking to improve standards of care, to raise awareness about how to best meet to the needs of this underserved group of patients, and to identify research priorities, so that clinical research is focused on the most important areas of unmet need.
Following the work of the ESO-ABC Task Force [11–14], created in 2005, and the successful undertaking of the 1st International Consensus Guidelines Conference on ABC (ABC1), held in November 2011, the 2nd International Consensus Conference for Advanced Breast Cancer (ABC2) took place in Lisbon, Portugal, on 7–9 November 2013. The conference brought together about 1100 participants from 71 countries, including health professionals, patient advocates, and journalists. A series of guidelines were discussed and agreed upon, based on the most up-to-date evidence, and can be used to guide treatment decision-making in diverse health-care settings globally. These guidelines are developed as a joint effort from ESO and ESMO (European Society of Medical Oncology), are endorsed by EUSOMA (European Society of Breast Cancer Specialists), SIS (Senologic International Society), and Flam (Federación Latino Americana de Mastologia), and organized under the auspices of UICC (Union Internationale Contre Le Cancer), OECI (Organization of European Cancer Institutes), and the BCRF (Breast Cancer Research Foundation).
While a number of new cancer therapies and diagnostic agents have been approved over the last year, especially targeted molecular treatments and agents that address the tendency of some newer drugs to lose effectiveness over time, the American Association for Cancer Research says in its 2014 annual cancer progress report that continued budget constraints on the National Institutes of Health will hamper new and ongoing research at a time that developing new treatments is critical.
During a telephone news briefing last week, the association’s leadership said that with an aging population, new cancer diagnoses can be expected to increase from 1.6 million this year to 2.4 million by 2035, and that developing new therapies as soon as possible is essential to address this expected surge. Half of all new cancer patients are over age 50.
AACR President Carlos Arteaga, MD, Director of the Center for Cancer Targeted Therapies at Vanderbilt-Ingram Cancer Center, noted that there has been tremendous progress in developing new treatments, from bench to bedside, over the last 25 years: “It is safe to say that we are seeing transformational changes in treatment, but the pace has slowed due to years of declining budgets at the National Institutes of Health and the National Cancer Institute,” he told reporters.
“This emphasizes the vital importance of federal funding of the NIH, and especially the NCI. If we are to fully realize the promise of science to transform cancer care, it will require leadership in Congress and from the Administration, to ensure that biomedical research becomes a priority… in order for [research] to grow at a robust pace to address the burden.”
Although universal insurance coverage for postmastectomy breast reconstruction has been mandated since 1998, a new study has found that the persistently high rates of American women who choose not to undergo reconstruction surgery are due primarily to patient preferences and not a lack of awareness.
Clovis Oncology CLVS, -0.24% today announced that its Phase 2 study of lucitanib in patients with FGF-aberrant, advanced breast cancer has commenced and the first patient dosed at a U.S. study site. Lucitanib is the Company’s oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 and 2 (FGFR1-2), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR a-ß).
“Early lucitanib data are encouraging, and suggest that determination of genetic alterations in the FGF pathway may be important to identify the patients most likely to benefit from lucitanib treatment,” said Professor Carlos L. Arteaga, MD, Associate Director for Clinical Research, Director of the Center for Cancer Targeted Therapies, and Director of the Breast Cancer Program at the Vanderbilt-Ingram Cancer Center of Vanderbilt University. “This study will further explore two doses of lucitanib in patients with FGF-aberrant breast cancer, a population which possesses these genetic alterations, and for whom new treatment options are needed.”
More and more women are choosing to aggressively treat a cancer diagnosis in one breast with a double mastectomy, but new research says that won’t make a difference in long-term survival rates. A large new study by the Stanford University School of Medicine and the Cancer Prevention Institute of California found that the rate of double mastectomies jumped from 2.0 percent in 1998 to 12.3 percent in 2013. But survival rates were similar to those who had the more targeted procedure of breast-conserving surgery — when just the malignant lump is removed, followed by radiation. The findings were published Tuesday in the Journal of the American Medical Association. “When faced with a new breast cancer diagnosis, many patients assume that they will achieve a survival advantage by pursuing the
"Presurgical application of a gel containing an active metabolite of tamoxifen was just as effective in inhibiting cell proliferation as oral tamoxifen in women with estrogen receptor-positive ductal carcinoma in situ (DCIS), but with lower levels in the blood and hence potentially fewer serious side effects, according to a small Phase II trial.
In the study, published in Clinical Cancer Research (2014;20:3672-3682), researchers tested the gel, which contains the breakdown product 4-hydroxytamoxifen (4-OHT), in 26 patients enrolled in the randomized, double-blind, placebo-controlled study, 12 of whom used the gel. After six to 10 weeks, the gel was found to reduce Ki-67, a key marker of cell proliferation in the breast, at rates comparable to those achieved with oral tamoxifen over a similar period of time.
The team, led by senior author Seema A. Khan, MD, Professor of Surgery at Northwestern University Feinberg School of Medicine, found equal amounts of 4-OHT in the breast tissue of patients in both the gel and oral arms (5.8 versus 5.4 ng/g, respectively) collected during surgery, but the level of 4-OHT in the blood of patients from the gel arm was 5.5-fold lower than in those in the oral tamoxifen arm (0.2 versus 1.1 ng/ml, respectively).
Oral tamoxifen decreases the risk of cancer recurrence in the same breast and secondary primary cancer in the other breast. Studies have shown, however, that as many as half of eligible women decline or fail to adhere to treatment out of concern for side effects, which can include an increased risk of thromboembolism, endometrial and uterine cancers, hot flashes, vaginal, and other symptoms.
Oral tamoxifen must be broken down by the liver into its active components, which include 4-OHT, but it then enters the bloodstream. Because of this, harmful side effects can arise, such as the activation of certain proteins that cause blood clots and increased risk of endometrial and uterine cancers.
“We found that applying the gel to the skin resulted in high drug levels in the breast but not in the blood, which mean that it maintains the effectiveness of the drug but should minimize serious side effects,” she said in an interview. “When the 4-OHT gel is applied directly to breast skin it is not directly metabolized by the liver, which should eliminate the risk of blood clots.”
"Years ago, women and men diagnosed with cancer did not dare speak publicly of their private torments. Over time, cancer care improved and survivors of the once-deadly disease increased. In particular, breast cancer moved from the shadows into daylight beginning with FLOTUS Betty Ford’s highly publicized battle and gaining ground from the many participants in walk-a-thons as well as the countless celebrities willing to discuss their ordeals.
In the closet no more, breast cancer is now the stuff of daily life for most Americans, as each of us seems to know somebody who has been diagnosed with this form of cancer. For this reason, it may come as a shock to learn that less than 42 percent of women choose breast reconstruction following their mastectomy. Researchers at Memorial Sloan Kettering Cancer Center led by Dr. Monica Morrow found in their new study of breast cancer patients the factors associated with foregoing reconstruction include being older, being black, and having a lower education level."
"Three to four years of treatment with bisphosphonates to boost bone density is not linked to a lowered risk of invasive postmenopausal breast cancer, concludes an analysis* of data published in JAMA Internal Medicine.
Some studies have suggested that bisphosphonates, which are commonly used to treat osteoporosis, may curb the risk of tumour growth and spread, while some observational studies have suggested bisphosphonates may protect women from breast cancer.
The researchers analysed the relationship between postmenopausal breast cancer and bisphosphonate use by looking at data from two randomised, double-blind, placebo-controlled trials.
The Fracture Intervention Trial (FIT) randomly assigned 6,459 women aged 55 to 81 to alendronate or placebo, with an average follow-up of 3.8 years.
The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7,765 women aged 65 to 89 to annual intravenous zoledronic acid or placebo for an average follow-up of 2.8 years."
"A dancer since the age of 4, Maggie Kudirka knows the grit, discipline and focus required to become a professional ballerina.
Now the same drive that kept her dancing may be what keeps her alive: at 23 years old, Maggie, who trains and performs at the prestigious Joffrey Ballet School, was diagnosed with Stage 4 breast cancer.
As she takes the biggest leap of her life—a leap of faith that an aggressive treatment will attack her cancer—Maggie has launched a social media campaign. What started with the Bald Ballerina Facebook page to inform friends and family of her health situation has turned into a platform for Maggie to raise awareness about breast cancer in young women and raise money to help pay for her medical expenses.
After her June 19 diagnosis, Maggie says her world took a surreal turn. A schedule of six hours a day of ballet training with fellow Joffrey dancers in New York abruptly ended, as Maggie moved back home to live with her parents in Ellicott City, Maryland, and begin treatment.
Susan Zager's insight:
According to the article a 2013 study published in JAMA found, "while it’s a relatively small number, metastatic breast cancer — disease that has spread to the bones or other organs — tripled among women younger than 40 between 1976 and 2006. And the incidence of advanced cancer has gone up fastest in younger women ages 25 to 34."
"My colleagues at Northern Westchester Hospital and I recently published research findings on breast reconstruction outcomes that have the potential to dramatically improve quality of life after breast surgery as well as to save women’s lives. Published in The American Journal of Cosmetic Surgery, our article was titled “Breast Reconstruction With or Without Human Acellular Dermal Matrices:
A Single-Clinic Review of Esthetic Outcomes and Risk Factors for Complications,” and co-authored by David A. Palaia, MD; Anthony C. Cahan, MD; Karen S. Arthur, MD; Danielle M. DeLuca-Pytell, MD; and Philip C. Bonanno, MD.
What makes our findings such good news for women – possibly for you, or someone you love? To understand their impact, let’s look at the context of the study for a moment:
Breast reconstruction has become increasingly important in the total treatment of women with breast cancer. Of course, the priority is to cure the cancer. However, re-establishing quality of life and making survivorship, the post-cancer portion of life, as normal as possible, is really the modern goal of cancer treatment. When the focus is on the woman with cancer – rather than the cancer – breast reconstruction becomes critically important."
"A new study in East Asian women has identified three genetic changes linked to an increased risk of breast cancer. The research, led by Vanderbilt University investigators, was published online July 20 in Nature Genetics.
While breast cancer is one of the most common malignancies among women worldwide, most studies of the genetic risk factors for the disease have focused on women of European ancestry.
Given the differences in genetic heritage and environmental exposures between East Asian women and those of European ancestry, the investigators decided to conduct a study in East Asians to search for genetic changes that are linked to breast cancer development. The current study was conducted as part of the Asia Breast Cancer Consortium led by Wei Zheng, M.D., Ph.D., MPH, Ingram Professor of Cancer Research at Vanderbilt.
First author Qiuyin Cai, M.D., Ph.D., associate professor of Medicine, and colleagues performed a genome-wide association study of 22,780 women with breast cancer, and 24,181 control subjects who were recruited in 14 studies in Asian countries, including China, Japan, Korea, Malaysia and Singapore.
DNA for the gene assays was obtained through blood samples or buccal cells from mouthwash.
"We found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk and we identified a possible association with a fourth gene locus," said Cai. "Two of those sequence changes are in parts of the genome that regulate the expression of nearby genes."
"As breast cancer prevention and therapy improve and the number of survivors rises, more women are living with long-term effects of treatment. Women with breast cancer learned about ways to cope with therapy-related side effects at the September 27 Annual Fall Conference of Living Beyond Breast Cancer, entitled “Breast Cancer Today: Individual Treatments, Shared Experiences,” in Philadelphia.
Among the various side effects that Virginia F. Borges, MD, MMSc, of the University of Colorado Cancer Center, Denver, spoke about, fatigue was underscored as a major problem.
Dr. Borges cited the National Comprehensive Cancer Network in her definition of fatigue as “a distressing, persistent, subjective physical, emotional and/or cognitive sense of tiredness or exhaustion related to cancer or its treatment that is not proportional to recent activity and interferes with usual functioning and different from usual fatigue as it is not relieved by rest and sleep.”
One-third of survivors up to 10 years out report significant, life-altering fatigue. Fatigue is rated on a scale of mild, moderate, or severe, with moderate fatigue requiring work-up, referrals, or treatment. The clinical picture consists of both objective and subjective components, including physical weakness or tiredness, depression or negative alteration of mood, lack of motivation or initiative, cognitive impairment, and a weakened ability to sustain relationships."
"Tamoxifen was approved by the FDA in 1977 to treat advanced breast cancer. In 1998, the Early Breast Cancer Trialists’ Cooperative Group published results showing that tamoxifen was effective in preventing breast cancer recurrence in patients whose tumors were estrogen receptor (ER)-positive or of unknown ER status,1 which led to an expansion of the drug’s indication.2 As effective as tamoxifen and other therapies have been, some breast tumors do recur. Despite the considerable scientific data and many successes in treating breast cancer, not much is known about recurrent breast tumors, other than that they can appear in almost any location in the body and at any time after remission is attained—even decades later.
A Cure or a Disease-Free Period?
The incidence of breast cancer has remained relatively stable since 2004.3 Declining incidence during the 1990s was attributed in part to lower utilization for estrogen replacement therapy for the treatment of menopausal symptoms.4
"NEW YORK - Procter & Gamble is canceling an on-field breast cancer awareness promotion it had been planning with the National Football League, the latest sponsor to respond to the NFL's growing problems.
The consumer products maker is the latest major sponsor, following PepsiCo and Anheuser-Busch, to show concern over the NFL's handling of domestic abuse allegations against several players.
Women make up 35 percent of the average audience of 17.4 million during a regular season NFL game, and the NFL has made it a point to reach out to women in recent years.
The league has made Breast Cancer Awareness month in October a particular focus. Part of its NFL Pink "Crucial Catch" campaign, in partnership with the American Cancer Society, features players, coaches and referees wearing pink game apparel, on-field pink ribbon stencils, special game balls and pink coins.
P&G's Crest brand had been working on a program with players from each of the NFL's 32 teams to wear pink mouthguards and participate in other activities.
"The American Society of Clinical Oncology (ASCO) today issued a new clinical practice guideline on chemotherapy and targeted therapy for women with HER2-negative advanced breast cancer. The guideline provides detailed, evidenced-based information on the efficacy and side effects of various therapies.
"In releasing this guideline, our aim is to improve both the length and quality of patients' lives," said Ann H. Partridge, MD, MPH, Founder and Director, Program for Young Women with Breast Cancer,Director, Adult Survivorship Program at Dana-Farber Cancer Institute and co-chair of ASCO's expert panel that developed the guideline. "Although no clear chemotherapy winner emerged – the guideline will help doctors and patients choose the best therapy based on what treatment would be most tolerable and convenient for the patient."
Nearly 80 percent of women with advanced breast cancer are HER2-negative, meaning that they have normal levels of HER2 protein in their tumor and are not candidates for HER2 targeted therapies. The new ASCO guideline assesses systemic therapy options for these women about to begin a chemotherapy treatment regimen."
"What causes cells to become mutated and develop into cancer can also be used as a form of cancer therapy.
DNA damage, when incorrectly repaired, leads to genomic instability and eventually cancer. However, therapies combined with adjuvant radiotherapy (DNA-damaging agent) have been demonstrated to improve the survival of triple-negative breast cancer (TNBC) patients. Nonetheless, the emergence of tumor cells resistant to such therapy, makes the development of new therapeutic strategies to overcome radioresistance and improve radiosensitivity crucial.
TNBC accounts for 15-20% of all newly diagnosed breast cancer cases, and is defined by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and minimal HER2 expression."
"NORTH ANDOVER — An amazing laugh. Dynamic blue eyes. A smile that lit up the room. These are the things Fiona Maguire will remember about her husband Peter Devereaux, a well-liked Marine and male breast cancer advocate who died Thursday after a six year battle with the illness. He was 52.
“He really had a great, light personality. He liked everyone. He was probably the least judgmental person you’d ever meet in your life,” Maguire said. “He never looked at people for money they made, or how they looked,or anything like that. He was really just a kind man.”
Devereaux became well known as an advocate for breast cancer patients through talks he gave at fundraisers in Greater Boston and beyond. Devereaux was part of the largest group of male breast cancer patients ever recorded: former Marines who were stationed at Camp Lejeune. At the North Carolina base, Marines and their families were exposed to toxic water from at least 1957 to 1987. Devereaux served four years with the Marines beginning when he was 18 and was stationed at Camp Lejeune for 16 months."
Susan Zager's insight:
Peter was pretty incredible.I was fortunate to meet him with other advocates at SABCS. Our prayers go out to all of his family and friends.
"Scientists have made it easier to predict both breast cancer relapses and responses to chemotherapy, through the identification of a unique gene. The newly found marker could help doctors classify each breast cancer patient and customize a treatment regimen that is more effective. The discovery was a collaborative effort by scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB), and the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS).
Despite advancements in cancer treatment, breast cancer remains the most common cancer among Singapore women. Thirty percent of early breast cancer patients in the world experience relapse due to metastasis, or the spread of cancer cells to other organs in the body. Some patients also do not respond well to chemotherapy. The inability to forecast relapses or the effectiveness of chemotherapy has led to a pressing need to identify predictive markers, which doctors can use to tailor appropriate treatment for each breast cancer patient at an early stage.
Mutations in the gene can make breast cancer up to nine times more likely to develop, an international team of researchers reports in this week’s New England Journal of Medicine.
About 5 to 10 percent of breast cancers are thought to be due to bad BRCA1 or BRCA2 genes. Beyond those, many other genes are thought to play a role but how much each one raises risk has not been known, said Dr. Jeffrey Weitzel, a genetics expert at City of Hope Cancer Center in Duarte, Calif.
The new study on the gene— called PALB2 — shows “this one is serious,” and probably is the most dangerous in terms of breast cancer after the BRCA genes, said Weitzel, one of leaders of the study.
It involved 362 members of 154 families with PALB2 mutations — the largest study of its kind. The faulty gene seems to give a woman a 14 percent chance of breast cancer by age 50 and 35 percent by age 70 and an even greater risk if she has two or more close relatives with the disease.
That’s nearly as high as the risk from a faulty BRCA2 gene, Dr. Michele Evans of the National Institute on Aging and Dr. Dan Longo of the medical journal staff write in a commentary in the journal.
The PALB2 gene works with BRCA2 as a tumor suppressor, so when it is mutated, cancer can flourish.
How common the mutations are isn’t well known, but it’s “probably more than we thought because people just weren’t testing for it,” Weitzel said. He found three cases among his own breast cancer patients in the last month alone.
Among breast cancer patients, BRCA mutations are carried by 5 percent of whites and 12 percent of Eastern European (Ashkenazi) Jews. PALB2 mutations have been seen in up to 4 percent of families with a history of breast cancer.
Men with a faulty PALB2 gene also have a risk for breast cancer that is eight times greater than men in the general population.
"The Cancer Drug Coverage Parity Act has been reintroduced and now has over 80 bi-partisan co-sponsors! But the work is not done yet. The more bi-partisan co-sponsors we have, the more likely the House will move to vote on this critical legislation.
We need you to reach out to your US Representative to ask him or her to co-sponsor HR 1801. The bill will require oral anticancer treatments to be covered at the same rate as IV treatments. Many insurance plans treat patient-administered anticancer treatments, like oral pills, differently than other forms of treatment creating a financial barrier to care for many myeloma patients.
By entering your information below, you will be able to quickly and easily email your US Representative a prewritten letter. After clicking next, take a moment to customize the letter with a personal story to increase your message's impact. You can share your story or click on the talking points to the right to add those into your message.
Thank you for your help ensuring cancer patients have fair and equal access to all types of treatments!"
Susan Zager's insight:
Please use the International Myeloma Association's prewritten letter to Congress and write to your representatives to support this important bipartisan legislation (HR 1801)/ It will assure that all cancer patients can receive oral as well as IV anti-cancer treatments treated the same way so that the oral medications are not a financial burden.
"TAIPEI--Taiwan-based OBI Pharma (浩鼎生技) announced Monday that its phase 2/3 stage clinical trial for a therapy for metastatic breast cancer, designated OBI-822, has met the goal of collecting 342 patients.
OBI Pharma Chairman Michael N. Chang (張念慈) said that the OBI-822 project has progressed more smoothly than expected, and the completion of the collection was a major milestone.
The company will analyze the data after the last patient completes the treatment process.
According to OBI Pharma General Manager Amy Huang (黃秀美), breast cancer is the most common form of cancer among women and the biggest killer of women's health.
The five-year survival rate for metastatic breast cancer is only 24.3 percent, Huang said, stressing that developing this first-class immunotherapy can hopefully satisfy this unmet medical need.
Susan Zager's insight:
According Huang, " the concept behind OBI-822, is to use the human body's immune system to fight cancer with few side effects, unlike chemotherapy and radiation therapy that harm good cells as well as cancerous cells."
(HealthDay)—Researchers have identified genes that may help predict whether a patient with estrogen receptor (ER)-positive breast cancer is likely to benefit from tamoxifen therapy, according to a study published in the July 15 issue of Cancer Research.
Hendrika M. Oosterkamp, M.D., of The Netherlands Cancer Institute in Amsterdam, and colleagues conducted a large-scale loss-of-function genetic screen in ZR-75-1 luminal breast cancer cells to identify candidate genes for tamoxifen resistance.
The researchers found that loss of function in the deubiquitinase USP9X prevented proliferation arrest by tamoxifen, but not by the ER downregulator fulvestrant. RNAi-mediated attenuation of USP9X stabilized ERα on chromatin in the presence of tamoxifen, and this caused a global activation of ERα-responsive genes driven by tamoxifen. A gene signature defined by differential expression after USP9X attenuation in the presence of tamoxifen was used to identify patients with ERα-positive breast cancer experiencing a poor outcome after adjuvant therapy with tamoxifen. Correlation of the gene signature with survival was not observed in patients with breast cancer who did not receive endocrine therapy.
"Overall, our findings identify a gene signature as a candidate biomarker of response to tamoxifen in breast cancer," the authors write.