Breaking Research News from sources other than Breastcancer.org
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from JAMA an editorial on reducing recurrence in early TN
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Stereotactic Ablative Body Radiotherapy in Patients With Oligometastatic Cancers
- The Lancet Oncology, January 07, 2021 The authors of this prospective National Health Service registry–based observational study evaluated the outcomes of 1422 patients with solid cancer extracranial oligometastatic disease treated with stereotactic ablative body radiotherapy. The 1- and 2-year overall survival rates were 92% and 79%, respectively. Grade 3/4 toxicity was rare.These real-world findings support both earlier trial data and this therapeutic approach in the selected patient population.
https://www.thelancet.com/journals/lanonc/article/...(20)30537-4/fulltext{Free access to reporting and abstract. Full article requires fee or subscription.}0 -
Oncotype DX Misses on Breast Cancer Risk in Black Women
— Accuracy of 21-gene recurrence score worse compared with white women
https://www.medpagetoday.com/hematologyoncology/breastcancer/90813
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Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer -- A Phase 3 Randomized Clinical Trial
JAMA Oncol. Published online January 22, 2021
Results A total of 536 patients were randomized to receive margetuximab (n = 266) or trastuzumab (n = 270). The median age was 56 (27-86) years; 266 (100%) women were in the margetuximab group, while 267 (98.9%) women were in the trastuzumab group. Groups were balanced. All but 1 patient had received prior pertuzumab, and 489 (91.2%) had received prior ado-trastuzumab emtansine. Margetuximabhttps://jamanetwork.com/journals/jamaoncology/full...improved primary PFS over trastuzumab with 24% relative risk reduction (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P = .03; median, 5.8 [95% CI, 5.5-7.0] months vs 4.9 [95% CI, 4.2-5.6] months; October 10, 2018). After the second planned interim analysis of 270 deaths, median OS was 21.6 months with margetuximab vs 19.8 months with trastuzumab (HR, 0.89; 95% CI, 0.69-1.13; P = .33; September 10, 2019), and investigator-assessed PFS showed 29% relative risk reduction favoring margetuximab (HR, 0.71; 95% CI, 0.58-0.86; P < .001; median, 5.7 vs 4.4 months; September 10, 2019). Margetuximab improved objective response rate over trastuzumab: 22% vs 16% (P = .06; October 10, 2018), and 25% vs 14% (P < .001; September 10, 2019). Incidence of infusion-related reactions, mostly in cycle 1, was higher with margetuximab (35 [13.3%] vs 9 [3.4%]); otherwise, safety was comparable.Conclusions and Relevance In this phase 3 randomized clinical trial, margetuximab plus chemotherapy had acceptable safety and a statistically significant improvement in PFS compared with trastuzumab plus chemotherapy in ERBB2-positive ABC after progression on 2 or more prior anti-ERBB2 therapies. Final OS analysis is expected in 2021.Trial Registration ClinicalTrials.gov Identifier: NCT02492711https://jamanetwork.com/journals/jamaoncology/full...
doi:10.1001/jamaoncol.2020.7932
{appears to be open access}0 -
Aspirin linked to better survival rates for bladder and breast cancer
https://www1.racgp.org.au/newsgp/clinical/aspirin-associated-with-better-survival-rates-for
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Unexpected Survival Benefit Reported With Trilaciclib in Metastatic Triple-Negative Breast Cancer https://ascopost.com/issues/january-25-2021/unexpe...
key points:
phase 2 trial reporting
pts were pre-treated
trilaciclib is an IV cdk4/6 inhibitor
was given w. gemcitabine plus carboplatin
"The outcome in the PD-L1–positive subset (57.6% of those tested) was notable, with overall survival of 32.7 months vs 10.5 (hazard ratio = 0.34; P = .004)."
"We plan to initiate a registrational trial for trilaciclib in mTNBC in 2021, with overall survival as the primary outcome measure"
More from the manufacturer here: https://www.g1therapeutics.com/pipeline/trilacicli...
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Large studies estimate breast cancer risk linked to specific genes
January 20, 2021
Two large studies published in the New England Journal of Medicine found pathogenic variants in BRCA1 or BRCA2 genes raise the carrier's risk for breast cancer by nearly eightfold or more than fivefold, respectively, and protein-truncating variants in BRCA1 was linked to a tenfold higher risk. Moderate breast cancer risk was also associated with mutations in PALB2, ARD1, RAD51C, RAD51D, ATM and CHEK2 genes, and specific genes were linked to risks for specific types of breast cancer.
CONCLUSIONS
This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer–predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.)
Reporting courtesy of AANP SmartBrief
https://www.medpagetoday.com/hematologyoncology/br...
https://apnews.com/article/us-news-genetics-cancer...
https://www.nejm.org/doi/full/10.1056/nejmoa200593...
DOI: 10.1056/NEJMoa2005936
{Coverage free of charge but may require registration; abstract w/o charge. Access to full article in NEJM requires fee or subscription.}
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Breast cancer: Androgen therapy shows promise in preliminary study
Scientists have embarked on renewed investigations into androgen therapy — a former breast cancer treatment. Recent research in mice shows that it may help block tumor growth.
....
Androgen therapy was practiced during the first half of the 20th century, according to a paper published in the American Journal of Cancer Research. Doctors stopped using it for breast cancer, though, when scientists determined that "Androgens can be converted to estrogens."
This led researchers to believe that androgen therapy could do more harm than good, since an increase in estrogen is linked with breast cancer.
However, in a recent study published in Nature Medicine, researchers decided to take another look at this use of androgens. The team discovered that this hormone may, after all, contribute to fighting breast cancer.
The researchers — many from the University of Adelaide, in Australia — studied the effect of androgen receptor-activating drugs on cell cultures and mouse models of breast cancer. In these mice, the scientists had implanted tumors extracted from patients with breast cancer.
They found that activating androgen receptors had a "potent" suppressive effect on different kinds of breast cancer tumors, even those that had been resistent to "traditional" treaments with estrogen receptor inhibitors and CDK4/6 inhibitors.
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Signatures of Mutational Processes and Response to Neoadjuvant Chemotherapy in Breast Cancer
- The authors of this retrospective analysis performed whole-exome sequencing on retreatment tumor samples in patients with previously treated, primary invasive HER2 negative breast cancer to evaluate the mutational signals which may be predictive of tumor response and resistance to neoadjuvant chemotherapy. Different breast cancer subgroups could be identified by differences in homologous recombination deficiency (HRD)–associated APOBEC-related mutations. For HR-positive tumors, the mutational signal S13 showed a strong correlation with an increased pathological complete response (pCR) rate while the S3 signal for HRD was borderline significant. Tumors with a high S13 signal had a median pCR of 22% versus 4% in tumors with low S13 levels. HR-positive tumors were noted to have signatures S3 and S4 associated with reduced disease-free survival, but these were nonsignificant in multivariate analysis. In contrast, HR-negative tumors had no mutational signatures associated with pCR.
- Whole-exome sequencing revealed that the clinical behavior of particular tumor types could be predicted by the mutational signatures. This requires validation and confirmation of relevant mutational signatures but may help to identify tumor types more rapidly responsive to neoadjuvant chemotherapy to inform treatment decisions.
{Free access to reporting and abstract. Full article requires subscription or fee.}0 -
There is an interesting Freakonomics Radio podcast called "How to fix the incentives in cancer research".
It focuses a bit on prostate cancer, but also gives general insight on cancer trials challenges and improving approaches.
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NCCN Shares New Guidance Principles for Vaccinating People with Cancer Against COVID-19
The committee's recommendations state that all people currently in active cancer treatment should get the vaccine, with some advice to consider regarding immunosuppression and timing. The full document can be found at NCCN.org/covid-19, along with other vital information about the impact of COVID-19 on cancer care.
The guidance acknowledges that although these vaccines have been shown to be safe in general populations, their effectiveness among cancer and transplant patients is not precisely known at present.
The panel will continue to meet regularly in order to refine the recommendations for these and other issues, as they come up.
https://www.nccn.org/about/news/newsinfo.aspx?News...
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Individualizing Surveillance Mammography for Older Patients After Treatment for Early-Stage Breast Cancer
Multidisciplinary Expert Panel and International Society of Geriatric Oncology Consensus Statement
January 28, 2021The first mammography guidelines for older survivors of breast cancer emphasize decision-making based on life expectancy.Conclusions and RelevanceIt is anticipated that these expert guidelines will enhance clinical practice by providing a framework for individualized discussions, facilitating shared decision-making regarding surveillance mammography for breast cancer survivors 75 years or older.doi:10.1001/jamaoncol.2020.7582{Abstract free, fee or subscription for full access.}0 -
Breast cancer now most common type of cancer
A World Health Organization report found that breast cancer, which has overtaken lung cancer as the most common type, accounted for 11.7% of new cases across the world last year. Obesity was a common risk factor for breast cancer among women, while high body mass index, tobacco and alcohol use, lack of physical activity, and low intake of fruits and vegetables contributed to nearly one-third of cancer deaths, according to the report.
https://www.reuters.com/article/health-cancer/brea...
{Free access to reporting. Summary courtesy of AANP.}
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The Genomic Landscape of Breast Cancer Brain Metastases
January 17, 2021 - The Lancet Oncology
- The authors of this systematic review of 164 patients from 13 studies evaluated the genomic landscape in breast cancer brain metastases. There were 268 mutated genes present in at least two samples and 22 of these were mutated in five or more samples. Pathway enrichment analysis demonstrated the involvement of these genes in breast cancer–related signaling pathways, regulation of gene transcription, cell cycle, and DNA repair. Of the 22 mutations, 15 were shown to be actionable drug targets. There was receptor discordance between the primary breast cancers and the brain metastases.
- When possible, brain metastasis samples should be obtained to guide targeted therapy.
https://www.thelancet.com/journals/lanonc/article/...(20)30556-8/fulltext{Free access to reporting and abstract. Fee or subscription for whole article.}0 -
this is not a specific study but I saw this and found it interesting that some studies are based off of false assumptions. Including a number of breast cancer studies.
”As an example of outdated science keeping its momentum, Pielke writes of a 2015 literature review of some 900 peer-reviewed studies on breast cancer using a cell line "derived from a breast cancer patient in Texas in 1976." But in 2007, he says, it was confirmed that it was a skin cancer line, not one related to breast cancer, and that even now it is being improperly used in breast cancer research“
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Wow. Guess it's trust but verify territory!
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for an article on the issue of breast cancer cell lines, which also discusses the MDA-MB-435 cells referred to above (controversial, but probably melanoma lines), see this article in Breast Cancer Research
https://breast-cancer-research.biomedcentral.com/a...
From a stage 4 pt perspective I find in vitro studies pretty useless as they're not going to yield clinical results quickly but from a theoretical perspective, they are a source of fascinating insight into what causes mutations and how we might affect them.
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There was a book written in the 1980s about the Henrietta Lacks cell line and cell line contamination and how it was covered up by scientists. The title is “A Conspiracy of Cells”
Also - https://pubmed.ncbi.nlm.nih.gov/19722756/
And https://www.discovermagazine.com/health/the-dirty-little-secret-of-cancer-research
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Surgery Could Boost Survival for Women With Advanced Breast Cancers: Study
Women with advanced breast cancer who undergo surgery to remove the tumor after chemotherapy or another type of systemic treatment may live longer than those who don't have surgery, a new study suggests.
The findings challenge a long-held belief that surgery confers little benefit for women with stage 4 breast cancer unless the cancer is causing pain, bleeding or other symptoms.
https://consumer.healthday.com/12-30-surgery-could...
SOURCES: Daleela Dodge, MD, associate professor, surgery, Penn State Cancer Institute, Hershey, Pa.; Stephanie Bernik, MD, chief, breast service, Mount Sinai West Medical Center, New York City, and associate professor, surgery, Icahn School of Medicine at Mount Sinai, New York City; Annals of Surgical Oncology, Oct. 30, 2020
(Reporting is free to access. Not sure about journal article.}
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Primary Trastuzumab-Resistance After (Neo)Adjuvant Trastuzumab-Containing Treatment for HER2-Positive Breast Cancer Patients
- In this retrospective study of 1096 patients with HER2-positive early-stage breast cancer who received (neo)adjuvant trastuzumab, the authors evaluated primary trastuzumab resistance outcomes, defined as a recurrence during or within 12 months of therapy. Among a total of 126 recurrences, 75 met the definition of primary trastuzumab resistance, which was associated with a worse prognosis and a lower response rate to subsequent trastuzumab-containing therapy.
- Primary trastuzumab resistance was associated with a poor prognosis, and further research is warranted to evaluate the optimal treatment strategy for these patients.
https://www.clinical-breast-cancer.com/article/S15...(20)30218-4/fulltext{Free access to reporting; fee or subscription for full article.}0 -
FDA Approves MARGENZA™
On December 16, 2020, the FDA approved margetuximab-cmkb (MARGENZA™, MacroGenics) in combination with chemotherapy, for the treatment of patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. This new approval is based on the SOPHIA trial.
FDA Approves Margetuximab for Metastatic HER2-Positive Breast Cancer
FDA Approves Margenza Plus Chemotherapy for Pretreated Metastatic HER2-Positive Breast Cancer
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Breast Cancer Brain Metastases: Clinical Challenges and Recent Advancements
At SABCS 2020, investigators shared current research findings and moreBy BCRF - January 5, 2021Researchers are addressing clinical challenges and exploring the biology of brain metastases to develop novel treatment strategies and combat this devastating occurrence.At this year's San Antonio Breast Cancer Symposium (SABCS), researchers gave an overview of the treatment landscape for patients with breast cancer brain metastases (BCBM) and highlighted some promising new areas for future research.https://www.bcrf.org/sabcs-2020-updates-on-breast-...
{Excellent and brief summary of latest research on BCBM. Free access to this reporting.} ...and a journal article.... Evolving treatment strategies of brain metastases from breast cancer: current status and future directionTher Adv Med Oncol. 2020; 12: 1758835920936117.Published online 2020 Jun 23. doi: 10.1177/1758835920936117Remarkable progress in breast cancer treatment has improved patient survival, resulting in an increased incidence of brain metastasis (BM). Current treatment options for BM are limited and are generally used for palliative purposes. Historically, local treatment, consisting of radiotherapy and surgery, is the standard of care due to delivery limitations of systemic treatments through the blood–brain barrier. However, as novel biological mechanisms for tumors and BM have been discovered, several innovative systemic agents, such as small-molecular-targeted therapy and immunotherapy, have begun to change the treatment paradigm. In addition, efforts to maximize antitumor effects have been attempted using combination therapy, informed by tumor biology. In this comprehensive review, we will highlight various clinical trials investigating the treatment of BM in breast cancer patients, discuss presently available treatment options, and suggest potential directions of future therapeutic targets.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC73133...
(Free access to full article!}0 -
Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.
The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer. This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective. Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients. BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
First published: 02 February 2021
Relevant trial: ClinicalTrials.gov (NCT04189211)
https://www.meta.org/papers/safety-tolerability-an...
https://onlinelibrary.wiley.com/doi/10.1002/cac2.1...
{Free access to abstract. Registration may be required. Free access to full article.}
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Fecal matter transplants could help certain cancer drugs work in more people, study shows
Checkpoint inhibitors like Keytruda and Opdivo can be incredibly powerful cancer-killing drugs — when they work, that is, which is less than 70% of the time. For years, scientists have hoped to find a way to identify a combination of therapies that might help these drugs work for a larger number of people.
New clinical trial results published Thursday in Science provide some of the strongest evidence yet for an unusual but promising mashup: pairing immunotherapy drugs with fecal microbiota transplants, or FMTs.
https://www.statnews.com/2021/02/04/fecal-matter-t...
New fecal microbiota for cancer patients
The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients.
Science, this issue p. 602, p. 595; see also p. 573 Science 05 Feb 2021: Vol. 371, Issue 6529, pp. 602-609
https://science.sciencemag.org/content/371/6529/60...
DOI: 10.1126/science.abb5920
{Fee for full articles. The topic was just too ... verboten... to pass up.}
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If it works, it works right? Facinating!
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Lumpie - thank you for the post on fecal matter, one more question to ask the DR. But it sounds so new, it is unlikely she would know much about it, also sounds like it might be drug/cancer specific. Gut health seems to be another area of contention.
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Interesting article on the benefit of green tea antioxidant in fighting cancer
https://www.technologynetworks.com/cancer-research/news/antioxidant-found-in-green-tea-may-increase-levels-of-p53-3455.
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This guy really drills into the cellular level of things
https://jonlieffmd.com/blog/intelligent-cancer-cells-communicate-with-exosomes
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Kanga re Green tea - a fast route is the supplement EGCG - the active ingredient. If you prefer the tea, Matcha is the best for this nutrient.
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Lumpectomy is associated with IMPROVED SURVIVAL compared with mastectomy for early stage breast cancer - A Propensity Score Matched Comparison Using the National Cancer Database
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