Breaking Research News from sources other than Breastcancer.org
Comments
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Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
- The authors of this 3 + 3 dose-escalation study enrolled 27 patients with metastatic HER2-positive metastatic breast cancer who had progressed on dual-antibody therapy (trastuzumab, pertuzumab) and a taxane. They were treated across four dose levels of neratinib in combination with ado-trastuzumab emtansine (T-DM1). An objective response was evident in 63% of evaluable patients. The responses were deeper and more durable in patients with cell-free DNA ERBB2 amplification. Dose-limiting toxicities included diarrhea and nausea.
- The recommended phase II dose for neratinib was 160 mg/day for this combination. Loss of the HER2 receptor and high expression of p95HER2 may explain the resistance to HER2 antibodies.
DOI: 10.1200/JCO.19.00858 Journal of Clinical Oncology0 -
Pyrotinib vs Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab
- The authors of this randomized phase II trial evaluated capecitabine plus either lapatinib or pyrotinib, an irreversible pan-ErbB inhibitor, in 128 patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab. The overall response rate was significantly better with pyrotinib (78.5%) than with lapatinib (57.1%). The median progression-free survival was also superior at 18.1 versus 7 months (HR, 0.36; P<.001) for the pyrotinib and lapatinib arms, respectively.
- A randomized phase III trial is ongoing to confirm these encouraging results.
- https://www.practiceupdate.com/C/88420/56?elsca1=emc_enews_topic-alert
- https://ascopubs.org/doi/10.1200/JCO.19.00108
- DOI: 10.1200/JCO.19.00108 Journal of Clinical Oncology
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Good News on Nipple-Sparing Breast Surgery
Korean study examined recurrence rates
Incidence of breast cancer recurrence in the nipple-areola complex (NAC) following nipple-sparing mastectomy (NSM) and immediate breast reconstruction was extremely limited over the long term, Korean investigators found, and cancers that did recur did not increase risk of distant metastases or compromise overall survival.
The findings suggest that biological features of the breast cancer tumor should be considered when planning nipple-sparing mastectomy.
https://jamanetwork.com/journals/jamasurgery/article-abstract/2749070
Wu Z, Kim H, Lee J, et al. Breast Cancer Recurrence in the Nipple-Areola Complex After Nipple-Sparing Mastectomy With Immediate Breast Reconstruction for Invasive Breast Cancer. JAMA Surg. Published online August 28, 2019. doi:10.1001/jamasurg.2019.2959
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New drug approval by the FDA -- can be used in breast cancer
https://www.practiceupdate.com/c/88121/3/1/?elsca1...
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{I looked up the article BevJen posted and thought I would add some highlights. Thx BevJen!}
FDA Approves Third Oncology Drug That Targets a Key Genetic Driver of Cancer, Rather Than a Specific Type of Tumor
The U.S. Food and Drug Administration today granted accelerated approval to Rozlytrek (entrectinib), a treatment for adult and adolescent patients whose cancers have the specific genetic defect, NTRK (neurotrophic tyrosine receptor kinase) gene fusion and for whom there are no effective treatments.
This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated.
The ability of Rozlytrek to shrink tumors was evaluated in four clinical trials studying 54 adults with NTRK fusion-positive tumors. The proportion of patients with substantial tumor shrinkage (overall response rate) was 57%, with 7.4% of patients having complete disappearance of the tumor. Among the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for nine months or longer. The most common cancer locations were the lung, salivary gland, breast, thyroid and colon/rectum.
Rozlytrek was granted accelerated approval. This approval commits the sponsor to provide additional data to the FDA. Rozlytrek also received Priority Review, Breakthrough Therapy and Orphan Drug designation. The approval of Rozlytrek was granted to Genentech, Inc.
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Checkpoint Inhibitors in the Neoadjuvant Treatment of Triple-Negative Breast Cancer
- Interview with Heather Lynn McArthur MD nterview by Farzanna S Haffizulla MD, FACP, FAMWA
- Discussion of new approaches to treating triple-Negative Breast Cancer
- September 02, 2019
- video and transcript - no charge, but sign in may be required.
- https://www.practiceupdate.com/C/84601/56?elsca1=emc_enews_topic-alert
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Appreciate the additional info Lumpie, and also Bevgen signposting
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New Target for Slowing Breast Cancer's Spread to Brain
scientists have identified a protein that plays a role in the metabolic reprogramming of some breast cancer cells, allowing them to survive when they spread to the brain... disabling this protein may represent a novel strategy to prevent and treat breast cancer brain metastases... The spread of breast cancer cells to the brain is correlated with the overexpression of human epidermal growth factor receptor 2 (HER2) in cancer cells, but the mechanisms driving this correlation were unknown. scientists combed through publicly available genomic databases, discovering that increased levels of the fatty acid-binding protein 7 (FABP7), a lipid-binding protein in the brain, correlated with lower survival and higher incidence of brain metastases in HER2-positive breast cancer patients. Notably, FABP7 is not found in elevated levels in the primary HER2-positive breast tumors, instead only found in tumor cells growing in the brain... In mouse models, the investigators found that disabling FABP7 prevented HER2-positive breast cancer metastasizing into the brain. FABP7 could be used in the future as a biomarker or therapeutic target for breast cancer patients. If high levels of FABP7 were detected in breast cancer patients, it might signal the patient is at risk for cancer spreading to their brain, and targeting or disabling FABP7 could be a promising strategy to prevent or treat breast cancer brain metastasis.
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Total Chemo Dose Still Matters in Breast Cancer
Worse survival with cumulative dose <85% of planned
August 20, 2019
- Failure to achieve a threshold cumulative dose of adjuvant chemotherapy for early breast cancer correlated with worse survival, particularly when dose reductions occurred early in treatment, a retrospective review of 1,300 patients showed.Patients who received less than 85% of the planned total cumulative dose (TCD) had significantly worse 5-year disease-free survival (DFS, P=0.025) and overall survival (OS, P<0.001), as compared with patients who received 85% or more of the planned TCD. "What surprised us the most was how dramatically early reductions in chemotherapy affect survival compared to later modifications," ... "This became even more apparent when patients were further separated based on chemotherapy dose cutoffs. Often the first cycle of chemotherapy can be difficult for patients, and oncologists must convey the need for maintaining initial dose intensity, while using other medications to control side effects and manage comorbidities."
- https://www.medpagetoday.com/hematologyoncology/chemotherapy/81721
- Primary Source Journal of the National Comprehensive Cancer Network Source Reference: Veitch Z, et al "Impact of cumulative chemotherapy dose on survival with adjuvant FEC-D chemotherapy for breast cancer" J Natl Compr Canc Netw 2019; 17: 957-971.
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{I generally refrain from posting alarmist, non-cancer-specific articles, but this is truly distressing, IMO, and not from flaky sources.}
How to Eat Less Plastic
Your food and water are contaminated with plastic. Here's why it's in the food system and how it could affect your health.
A recent study indicates that the average person consumes a credit card-sized amount of microplastics — the tiny particles of plastics we ingest by eating, drinking, and breathing — every week. The chemicals found in these plastics are linked to harmful health effects, like various cancers, weakened immune systems, and reproductive problems. Find out 6 ways you can reduce unnecessary exposure to potentially harmful plastics.
https://doi.org/10.1021/acs.est.9b01517
https://pediatrics.aappublications.org/content/142/2/e20181410
PubMed 30037972
https://cues.rutgers.edu/2019-microplastics-conference/2019-mpc-dwnld.html
https://www.consumerreports.org/food-safety/gras-hidden-ingredients-in-your-food/
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[Discovery of] A molecule that regulates the development of cancer in a variety of human tumors [including breast]
Sonia Guil, leader of the Regulatory and Chromatin RNA group of Josep Carreras Leukemia Research Institute, and Lourdes Farré of ProCURE (Idibell) have discovered an intermediate molecule expressed from a region of the non-coding genome that is key to the development and differentiation of cells, and for the expansion of tumor cells...
The non-coding sequence that originates RPSAP52, is just "in front" of HMGA2. It has been discovered that it regulates the chain of events responsible for the increase in the number of tumor cells and the expansion of cancer tissues...
The study was carried out by combining in vitro approaches with in vivo studies on animal models. The tumorigenic role of RPSAP52 in breast and sarcoma tumors has been confirmed, and it can also have predictive value as a biomarker...
"For translational research, the findings are significant because these types of molecules are often present at low levels. Therefore they can be attacked and eradicated more easily than the coding genes," says Guil.
The next steps to move forward in this line of research will focus on generating in vivo tumor models and test small molecules that destroy RPSAP52 to study its effect on tumor growth.
Article: https://medicalxpress.com/news/2019-09-molecule-cancer-variety-human-tumors.html
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Is there a reliable site for finding out about clinical trials as well as alternative treatments. I guess my onciologist should know about clinical trials. I may be facing round 3, and just do not think I can go through traditional treatment. For me it does not seem to work. 2009 lumpectomy, radiation, 2 nodes removed; tamoxifen for 5 years; 2016 bi-lateral, 2 nodes removed, cancer only on left side, I opted for bi-lateral, chemotherapy, started with arimidex and stopped after several months due to SE, several months later started tamoxifen. Now it looks like there might be something in the right axilla. The radiologist I just saw said she went through the notes and had been the one to examine the tissue fomr the bi-lateral, and the R-side was clean at that time. One problem with clinical trials, you do not know if you get the placebo or not.
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I like this site for breast cancer clinical trials:
You can also go to
https://clinicaltrials.gov/ct2/home
Unless you are at a major research center or your MO has an interest in research, there is a good chance that s/he will not know about specific trials. MO's usually have a lot to keep up with and keeping tabs on the current recruitment status of hundreds of clinical trials may not be their thing. If you find one that you think may be suitable, you can always contact the trial for more info and/or ask your MO about it.
Please note, for stage IV clinical trials you should NEVER be given a placebo! Depending on the phase of study, you would either definitely be given the trial drug or you may be in a study comparing standard of care (or "physician's choice") to a new therapy. It is not an ethical practice to deprive stage IV patients of treatment.
Here's a link for more clinical trial info:
https://www.mbcalliance.org/mbc-alliance-cted This site provides links to additional good resources on clinical trials.
I don't do that much research on alternative treatments, but if I wanted to investigate, I would start with the web site for the National Associations for Naturopathic Doctors
https://aanmc.org/national-associations/
and look for info for the public on Basyr's site:
Also peer reviewed journals and nursing research may provide good information. Good luck!
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Just reiterating Lumpie's point on stage IV trial patients.....at no point should a stage IV patient be given a placebo.... if that is even suggested bin the trial.
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Breast cancer: Hormone therapy may only put some cells to 'sleep'
Published Tue 3 Sep 2019
https://www.medicalnewstoday.com/articles/326226.p...0 -
Proton Beam Radiation in Patients With Breast Cancer Requiring Regional Nodal Irradiation
- The authors of this phase II trial provide the first prospective evaluation of proton beam radiotherapy (RT) in breast cancer, evaluating proton beam RT in 70 patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics but were considered suboptimal candidates for conventional RT. This approach was associated with low toxicity and similar rates of disease control compared with historical conventional radiotherapy data.
- With better awareness of cardiac morbidity in this patient population, confirmation of these findings in a randomized phase III trial (RadCOMP Consortium Trial) will be important.
CONCLUSION: Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.
https://www.practiceupdate.com/C/88796/56?elsca1=emc_enews_topic-alert
https://ascopubs.org/doi/10.1200/JCO.18.02366
DOI: 10.1200/JCO.18.02366 Journal of Clinical Oncology
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More targeted, less toxic: The golden future of cancer treatment
Researchers have engineered gold-based molecules that target cancer cells and leave healthy cells unharmed, in a critical step towards precision cancer drugs with fewer toxic side effects. Pre-clinical studies have shown the molecules were up to 24 times more effective at killing cancer cells than the widely used anti-cancer drug cisplatin and were also better at inhibiting tumour growth...
Significantly, the synthetic molecules are built with resistance-fighting features to keep them effective over time, unlike current chemotherapies.
The study by researchers at RMIT University, detailing four new bio-active molecules and their effectiveness against five types of cancer cells [prostate, breast, cervical, melanoma and colon cancer], is published in Chemistry—A European Journal...
In addition, the molecules have strong anti-inflammatory properties, giving them a dual therapeutic effect and potential application in the treatment of chronic inflammatory conditions like arthritis...
The research team has completed successful in vitro and in vivo pre-clinical studies and is seeking funding to support the next stage of the research—clinical studies and regulatory approval.
Article: https://medicalxpress.com/news/2019-09-toxic-golden-future-cancer-treatment.html
Study: https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201903388
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Opinion: Are 71 NCI-Designated Cancer Centers Too Many?
In an opinion piece in The Scientist, David Rubensen argues that the National Cancer Institute (NCI) designated cancer center program "has evolved into a nationwide branding exercise, mostly signifying grant-writing endurance and adherence to metrics that skew scientific priorities and place centers in organizational straight jackets." He suggests questions that he believes should be addressed about the future of the program.
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Durvalumab in Combination With Trastuzumab in HER2‐Positive Metastatic Breast Cancer - no clinical activity
- This phase Ib trial was designed to evaluate the toxicity and activity of durvalumab in combination with trastuzumab among 14 patients with previously treated HER2-positive metastatic breast cancer (MBC). There was no significant activity observed with this regimen among HER2-positive, PD-L1–negative patients; 29% of patients experienced stable disease at 6 weeks.
- Durvalumab in combination with trastuzumab demonstrated no clinical activity among patients with heavily pretreated HER2‐positive PD‐L1–negative MBC.
doi:10.1634/theoncologist.2019-03210 -
Metronomic Chemotherapy for Advanced Breast Cancer
Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety.
- This retrospective study is a real-world analysis of metronomic chemotherapy for patients with metastatic breast cancer. The highest overall response rate was observed among patients receiving vinorelbine-based regimens. The median time to treatment failure was 6.28 months. The longest median progression-free survival was observed with vinorelbine-based regimens (9.5 months) and capecitabine as a single agent (10.7 months).
- The authors provide real-world data to inform the use of metronomic chemotherapy among patients with metastatic breast cancer.
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One MO doing this is Dr Keith Block in the Chicago area. He is able to treat people who other MOs think have had too much chemo or are too weak for more, by giving a low dose over 24 hours from a fanny pack. (And other innovative deliveries.) Also the chemo can be pulsed when it is most bioavailable/when the cancer is the most active in the 24 hour circadian clock aka "chronomodulation." I actually found out that Taxotere is most bioactive at 5-6 am and carboplatin at 4 pm. (I emailed a researcher in London to find this out.) So I got my Taxotere at 8 am and my carboplatin at 4 pm. They just taped me off in between.
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santabarbarian: Thanks for sharing your experience. This is an interesting approach and I suspect that it may allow those not otherwise able to tolerate chemo to benefit from this therapy. I have known patients who received low(er?) dose continuous infusion, namely, pregnant women, and have wondered if alternative approaches to the more "usual" infusion schedules had been studied in others.
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I would like to contribute a bit, my first try here among all these incredibly helpful posts... I hope this may be interesting...
There is a promising agent being tested here in the EU, called MitoTam, which is a mitochondrialy targeted Tamoxifen. It has just entered phase II trials
https://cancerres.aacrjournals.org/content/79/4_Supplement/P6-18-20
Mentioned in this article: Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity
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Study confirms low fat diets benefit women's health
Published Mon 9 Sep 2019
By Ana Sandoiu
Fact checked by Gianna D'Emilio
New research spanning over almost 2 decades finds that a low fat diet benefits women's health.
A low fat diet that includes lots of fruits and vegetables benefits women's health in the long run, according to new research.
Older studies in rats and mice have found that rodents on a high fat diet develop more tumors than those on a low fat diet.
Some of these studies referred to colorectal cancer in particular, while othersshowed that high fat diets boosted tumor growth in mouse models of breast cancer.
More recently, studies in humans have suggested that following a low fat dietary plan could improve the health and lifespan of women who have received a diagnosis of breast cancer.
Read more athttps://www.medicalnewstoday.com/articles/326286.p...
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Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?
- This retrospective study was designed to characterize nodal burden among breast cancer patients with axillary nodal metastases detected by ultrasound‐guided fine‐needle aspiration cytology (US‐FNAC) undergoing axillary dissection. Patients with one or two nodes had favorable pathologic characteristics, including a smaller primary tumor, a lower proportion of grade 3 invasive lobular disease, and a high proportion of low-Ki67 tumors. The median number of metastatic nodes was five. Among patients with clinically negative axilla, 50% had four or more metastatic nodes and 31% had fewer than three metastatic axillary nodes.
- Approximately one-third of patients with clinically negative axilla with positive axillary US-FNAC performed due to imaging results have fewer than three metastatic axillary nodes and hence could avoid axillary dissection, per the current guidelines.
https://www.practiceupdate.com/C/88865/56?elsca1=emc_enews_topic-alert
DOI: 10.1111/tbj.13479
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Thanks JaBoo. That sounds encouraging.
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Why Aren't Cancer Drugs Better? The Targets Might Be Wrong
Drugs can stop cancer cells if they attack the right proteins. But many of these targets were chosen with dated, imprecise technology, a new study suggests.
{NYT generally allows access to a limited number of articles per month without a subscription.}
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Scientists have determined a new way to protect the hair follicle from [taxane] chemotherapy in an effort to prevent hair loss as a result of cancer treatments.
...we found that CDK4/6 inhibitors can be used temporarily to halt cell division without promoting additional toxic effects in the hair follicle. When we bathed organ-cultured human scalp hair follicles in CDK4/6 inhibitors, the hair follicles were much less susceptible to the damaging effects of taxanes..."
The team hope that their work will support the development of externally applicable medicines that will slow or briefly suspend cell division in the scalp hair follicles of patients undergoing chemotherapy to mitigate against chemotherapy-induced hair damage. This could complement and enhance the efficacy of existing preventive approaches i.e. scalp cooling devices.
Article: https://www.sciencedaily.com/releases/2019/09/190912120535.htm
Reference: https://www.embopress.org/doi/full/10.15252/emmm.201911031
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Breast cancer cells 'stick together' to spread through the body during metastasis
"The good news," he says, "is that our study reveals that the process of metastasis, even in ideal laboratory settings, appears to be exceedingly inefficient." Research suggests that about 99% of cells that leave primary tumors die and never form new tumors.
https://www.sciencedaily.com/releases/2019/09/1909...0 -
Breast cancer cells 'stick together' to spread through the body during metastasis
"The good news," he says, "is that our study reveals that the process of metastasis, even in ideal laboratory settings, appears to be exceedingly inefficient." Research suggests that about 99% of cells that leave primary tumors die and never form new tumors.
https://www.sciencedaily.com/releases/2019/09/1909...0
