Breaking Research News from sources other than Breastcancer.org
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Timelines Matter in the Treatment of Breast Cancer
Patients who received chemotherapy more than 120 days after being diagnosed with breast cancer had significantly worse overall survival compared with those who received chemotherapy within 120 days, reported a large retrospective analysis in the Annals of Surgical Oncology...
The analysis showed that regardless of surgery type, patients who started chemotherapy beyond 120 days from the time of diagnosis had worse overall survival compared with patients who started chemotherapy within 120 days (hazard ratio [HR]=1.29; 95% CI, 1.22–1.37; P<0.001).
The association of worse survival and chemotherapy treatment delays was consistent across tumor subtypes evaluated, with HER2-positive disease most affected (HR=1.47; 95% CI, 1.29–1.68), followed by triple-negative breast cancer (HR=1.23; 95% CI, 1.10–1.38) and hormone receptor-positive and HER2-negative disease (HR=1.23; 95% CI, 1.13–1.34).
"The take-home message is try to get your chemotherapy in as early as possible," Shapiro said.
Article: https://www.cancernetwork.com/news/timelines-matter-treatment-breast-cancer
Study: https://link.springer.com/article/10.1245%2Fs10434-019-07566-7
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New St. Gallen International Breast Cancer Guidelines Recommend Oncotype DX Breast Recurrence Score® Test to Guide Chemotherapy for Node-negative and Node-positive Early-stage Breast Cancer
...In particular, the panelists recognized the value of the landmark TAILORx study results and noted that women with node-negative cancers and Recurrence Score® results ≤25 do not need chemotherapy.3 This group represents up to about 80% of patients who may be safely spared chemotherapy. The Breast Recurrence Score test also identifies those patients (with results of 26 to 100) who may receive a life-saving benefit from chemotherapy...
The new St. Gallen International Consensus guidelines, "Estimating the benefits of therapy for early stage breast cancer," were recently published online in the Advance Access section of Annals of Oncology and will appear in a future print issue...
Over the last several months, results of the TAILORx study have influenced positive treatment guideline updates distinguishing the Oncotype DX Breast Recurrence Score test from prognostic-only tests based on clinical evidence and the critical importance of predicting chemotherapy benefit. This includes the recent update to ASCO guidelines, which increased the proportion of women who can be effectively treated without chemotherapy based on the Recurrence Score results, highlighting the importance of testing all medically eligible early-stage breast cancer patients with the Breast Recurrence Score test. The National Comprehensive Cancer Network (NCCN) updated its guidelines in 2018 to categorize the Breast Recurrence Score test as the only "preferred" test for chemotherapy treatment decision-making for patients with node-negative, early-stage breast cancer. NCCN also classified the Breast Recurrence Score test as the only test that is predictive of chemotherapy benefit.
Article: https://finance.yahoo.com/news/st-gallen-international-breast-cancer-120000449.html
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Are there any benefits to continuing trastuzumab after disease progression in patients with HER2+ metastatic breast cancer?
A Pooled Analysis of 2618 Patients Treated With Trastuzumab Beyond Progression for Advanced Breast Cancer
In HER2+ MBC, continuing trastuzumab (T) after the progression during a first-line T-based regimen, represents 1 of the possible strategies, even if few data from randomized trials exist in this setting.A total of 29 studies (4 randomized controlled phase III trials, 2 observational studies, 8 prospective nonrandomized trials, and 15 retrospective case series) were retrieved for a total of 2618 patients. All were treated with a second-line, T-based treatment beyond progression with a first-line T-based chemotherapy. Overall, the median RR, TTP, and OS obtained from the selected articles were 28.7%, 7, and 24 months.Conclusions: This pooled analysis confirms that continuing T beyond the first progression continues to be 1 of the effective and preferred choices in HER2+ MBC, failing a (T-based) first-line regimen.Clinical Breast Cancer Volume 13, Issue 2, April 2013, Pages 81-87{NOTE: This is OLD research but it is interesting and I had never read it before....and it came out in a news blast for some reason. An oncologist was mentioning to me recently that, especially if there is a solitary lesion that progresses, it is possible that only that lesion has morphed into a different type of cancer and that the Herceptin (&/or Perjeta) is still controlling the HER2+ cancer.}0 -
How diabetes can increase cancer risk
"It's been known for a long time that people with diabetes have as much as a 2.5-fold increased risk for certain cancers," says John Termini, Ph.D., who is presenting the work at the [American Chemical Society (ACS) Fall 2019 National Meeting & Exposition]. These cancers include ovarian, breast, kidney and others...
He wondered if the elevated blood glucose levels seen in diabetes could harm DNA, making the genome unstable, which could lead to cancer. So Termini and colleagues looked for a specific type of damage in the form of chemically modified DNA bases, known as adducts, in tissue culture and rodent models of diabetes. Indeed, they found a DNA adduct, called N2-(1-carboxyethyl)-2'-deoxyguanosine, or CEdG, that occurred more frequently in the diabetic models than in normal cells or mice. What's more, high glucose levels interfered with the cells' process for fixing it. "Exposure to high glucose levels leads to both DNA adducts and the suppression of their repair, which in combination could cause genome instability and cancer," Termini says...
They wanted to determine the molecular reasons why the adducts weren't being fixed properly by the cells. They identified two proteins that appear to be involved: the transcription factor HIF1α and the signaling protein mTORC1, which both show less activity in diabetes...
According to Termini, several drugs that stimulate HIF1α or mTORC1 already exist. The researchers plan to see if these drugs decrease cancer risk in diabetic animal models, and if so, they will test them in humans. Termini notes that metformin, a common diabetes medication that helps lower blood glucose levels, also stimulates DNA repair. "We're looking at testing metformin in combination with drugs that specifically stabilize HIF1α or enhance mTORC1 signaling in diabetic animal models," he says.
Article: https://medicalxpress.com/news/2019-08-diabetes-cancer.html
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Oh no!
Menopause. 2016 May;23(5):584-6. doi: 10.1097/GME.0000000000000593.
Yoga increased serum estrogen levels in postmenopausal women-a case report.
Abstract
OBJECTIVE:
This case report aimed to evaluate 4 months of yoga practice on the quality of life (QOL) and estradiol levels of two postmenopausal women.
METHODS:
Participants were clinically healthy postmenopausal women, with follicle-stimulating hormone levels greater than or equal to 30 mIU/mL and a body mass index lower than 30 kg/m. The participants practiced yoga for 4 months in two 1-hour sessions per week.
RESULTS:
The participants exhibited an abnormal estrogen-level increase after 4 months of yoga practice and showed QOL improvements.
CONCLUSIONS:
In some cases, yoga practice can affect the female neuroendocrine system, increasing estrogen and improving QOL.
- PMID:
- 26926324
- DOI:
- 10.1097/GME.0000000000000593
- [Indexed for MEDLINE]
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debbew, that's very interesting. I've been wondering if there is something magical about metformin in reducing risk, or if the magic is in controlled glucose levels. "Exposure to high glucose levels leads to both DNA adducts and the suppression of their repair, which in combination could cause genome instability and cancer," Termini says... So it sounds like the magic of metformin is in the control, and not necessarily otherwise. If you can control your glucose with diet and exercise, that might be enough to reduce risk.
Feel free to correct me if I didn't interpret this correctly.
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MountainMia, I'm no expert at any of this, but I'm also interested in the benefits of controlling glucose levels and/or the benefits of metformin. The article exposed a new mechanism of action by which controlling glucose by any means (e.g. diet and exercise) should reduce cancer risk (less DNA damage, better repair). This may be in addition to other potential mechanisms (e.g. less insulin stimulating growth).
I think the researcher mentions metformin as one possible intervention to study for controlling glucose but mentions in passing that metformin "also stimulates DNA repair." I don't think that undermines the possible benefit of controlling glucose through other means. But metformin may also have some additional "magic." Several potential anti-aging effects of metformin are currently being studied in the TAME trial: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943638/
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Identifying Women at High Risk of Advanced Breast Cancer for Discussion of Supplemental Imaging
- JAMA internal medicine In this study, the authors prospectively assessed 638,856 women between 40 and 74 years of age undergoing routine screening to identify those at high risk of advanced breast cancer. The rates of advanced cancer were higher among women with heterogeneously dense breasts and with a 5-year BCSC breast cancer risk of ≥2.5%. The rate of advanced cancer was also higher among women with extremely dense breasts and a 5-year BCSC breast cancer risk of ≥1%.The authors suggest that breast density notification should go out with the notification of breast cancer risk to women at highest risk fo advanced disease, winnowing out women who do not need supplemental imaging, and serving as an effective platform upon which to base a discussion regarding supplemental imaging among women who do.https://www.practiceupdate.com/C/86192/56?elsca1=emc_enews_topic-alerthttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2737320doi:10.1001/jamainternmed.2019.1758
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Docs Brace for Medicare 'Appropriate' Imaging Rule
With deadline just 4 months away, fears of unreadiness and unintended consequences abound
As the medical community braces for implementation of the Protecting Access to Medicare Act (PAMA) by the Jan. 1, 2020 deadline, some wonder if it's even feasible or if another program delay is on the horizon.
The policy, aimed at reducing unnecessary testing, mandates that all advanced diagnostic imaging orders go through an algorithm that provides key confirmation codes required when Medicare is billed later on for the service.
Dubbed a "clinical decision support mechanism" (CDSM), this software processes each CT, MRI, nuclear medicine, and PET order before spitting out its verdict to the ordering professional: "appropriate," "maybe appropriate," or "rarely appropriate," according to a certain set of appropriate use criteria (AUC).
...the CDSM confirmation code provides proof that the ordering physician consulted AUC. Eventually, Medicare will not pay claims or advanced imaging without these codes.
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Mountain Mia if you look at Jane McClelland's book "How to starve cancer" Metformin interferes with multiple pathways by which cancer cells manage to eat. Not just glucose, but also glutamine and Fatty Acid pathways. It has more than one beneficial effect.
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"Diagnosis," new Netflix series
{I received this message about a new Netflix series. Since some of us have encountered "complexities" with getting an accurate diagnosis, I thought that this might be of interest.}
Doctors always hope for an easy diagnosis. It means we can provide the right treatment and a hopeful path to recovery. But human bodies are complicated. Debilitating fatigue on top of a full-body rash? Sometimes symptoms don't point to a clear diagnosis.
That's when we approach medicine like detectives. We have to understand a patient's story, uncover clues and solve the mystery of the illness. Then, we can get the patient's life back on track.
In my 17 years writing for The New York Times Magazine, I've described some fascinating cases. I'm thrilled to bring more cases to life in a new Netflix series "Diagnosis." In each episode, we meet a patient and harness the power of readers like you to help arrive at a diagnosis.
My hope is that the series will give viewers a sense of the obstacles we face in medicine, and how we overcome them — because no patient should ever struggle alone.
Thanks for reading (and watching).
Lisa Sanders, M.D., contributing writer for The New York Times Magazine and associate professor at the Yale University School of Medicine.
Link to trailer here:
https://www.nytimes.com/2019/07/22/magazine/diagnosis-tv-netflix-lisa-sanders.html?smid=rd
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Lumpie: Thanks for the imaging parameters article. I'm going to push even harder for an MRI before year end based on my specific circumstances.
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Photobiomodulation therapy for the management of radiation-induced dermatitis : A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery.
https://reference.medscape.com/medline/abstract/28243723
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Bioengineering (Basel). 2018 Jun 9;5(2). pii: E44. doi: 10.3390/bioengineering5020044.
Photobiomodulation Therapy (PBMT) in Peripheral Nerve Regeneration: A Systematic Review.
Abstract
Photobiomodulation therapy (PBMT) has been investigated because of its intimate relationship with tissue recovery processes, such as on peripheral nerve damage. Based on the wide range of benefits that the PBMT has shown and its clinical relevance, the aim of this research was to carry out a systematic review of the last 10 years, ascertaining the influence of the PBMT in the regeneration of injured peripheral nerves. The search was performed in the PubMed/MEDLINE database with the combination of the keywords: low-level laser therapyAND nerve regeneration. Initially, 54 articles were obtained, 26 articles of which were chosen for the study according to the inclusion criteria. In the qualitative aspect, it was observed that PBMT was able to accelerate the process of nerve regeneration, presenting an increase in the number of myelinated fibers and a better lamellar organization of myelin sheath, besides improvement of electrophysiological function, immunoreactivity, high functionality rate, decrease of inflammation, pain, and the facilitation of neural regeneration, release of growth factors, increase of vascular network and collagen. It was concluded that PBMT has beneficial effects on the recovery of nerve lesions, especially when related to a faster regeneration and functional improvement, despite the variety of parameters.
KEYWORDS:
low-level laser therapy; nerve regeneration; peripheral nerve repair; photobiomodulation therapy; tissue regeneration
- PMID:
- 29890728
- PMCID:
- PMC6027218
- DOI:
- 10.3390/bioengineering5020044
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Diverse immune cell profiles and roles found in breast cancer resistance to immunotherapy
With the goal of better understanding the role immune cells within tumors play in tumor growth and in response to therapy, Zhang and his colleagues conducted a series of analyses to characterize the immune cell composition of tumor microenvironments in eight murine models and in clinical datasets of triple negative breast cancers...
The researchers found large diversity in the frequency of neutrophils and macrophages among the tumor samples, including some tumors that preferentially attracted macrophages, while others attracted more neutrophils. The predominance of one cell type over the other can be explained in part by the type of molecules produced by the tumor. As Zhang explained, some tumors secrete molecules that attract macrophages, while other tumors produce other molecules that lure neutrophils to the tumor site...
Exploring the roles macrophages and neutrophils play in tumor growth revealed that in some tumors macrophages favored tumor growth, while in others they helped control it. Neutrophils, on the other hand, tended to promote tumor growth.
"These findings are just the beginning. They highlight the need to investigate these two cellular types deeper. Under the name 'macrophages' there are many different cellular subtypes and the same stands for neutrophils," Zhang said. "We need to identify at single cell level which subtypes favor and which ones disrupt tumor growth taking also into consideration tumor heterogeneity as both are relevant to therapy."
Article: https://medicalxpress.com/news/2019-08-diverse-immune-cell-profiles-roles.html
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DEPRESSION, ANXIETY LINKED TO OPIOID USE IN OLDER WOMEN WITH BREAST CANCER
Elderly women battling breast cancer who have anxiety, depression or other mental health conditions are more likely to use opioids and more likely to die, a new study led by the University of Virginia School of Medicine has found.
https://news.virginia.edu/content/depression-anxiety-linked-opioid-use-older-women-breast-cancer?
Mental Health Comorbidities and Elevated Risk of Opioid Use in Elderly Breast Cancer Survivors Using Adjuvant Endocrine Treatments
Journal of Oncology Practice Published online July 19, 2019
CONCLUSION:
The presence of mental health comorbidity in breast cancer survivors significantly increases the risk of opioid use and mortality, which highlights the need for better management of comorbid mental health conditions.
https://ascopubs.org/doi/10.1200/JOP.18.00781
{Thanks to Ingerp for sharing this article.}
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Fake news? I don’t trust the opioid and elderly women article just posted. Exactly howmany breast cancer patients overdose on opioids? And since when do doctors acknowledge that breast cancer CAUSES anxiety? Another way to take pain treatment away from those who seriously need it.
Last paragraphs say
The researchers noted potential limitations to their study such as a lack of information on the opioids used and a lack of details on the patients' pain assessments. They also suggest that mental health conditions such as depression may be underdiagnosed and that, as a result, the research may underestimate the percentage of patients with those conditions.
Tan disclosed potential conflicts of interest including owning stock in and receiving compensation from biopharmaceutical company Merck. Balkrishnan disclosed that he has done consulting or advising for Merck.
To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.
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Novel therapy studied for inherited breast cancer
A tiny molecule called microRNA (miR) 223-3p prevents normal cells from making mistakes while repairing their DNA. However, cancers with BRCA1 mutations repress miR223-3p to permit their cells to divide. Adding back miR223-3p forces the BRCA1-mutant cancer cells to die, said study co-author Patrick Sung...
There is evidence that restoring miR223-3p before cells convert to cancer can even prevent BRCA1-related disease, he said.
Article: https://www.sciencedaily.com/releases/2019/08/190827153106.htm
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FDA: Men Should Be Included in Breast Cancer Clinical Trials
"Less than 1 percent of all breast cancer cases occur in men, but men are more likely to be diagnosed at an older age and have a more advanced stage of disease. As breast cancer in men is rare, they have typically not been included in clinical trials for breast cancer treatment," according to an FDA news release. "This has led to a lack of data, so their treatment is generally based upon studies and data collected in women. While some FDA-approved treatments are gender-neutral in their indication, many therapies are only approved for women and further data may be necessary to support labeling indications for men."
The public comment period for the draft guidance ends Oct. 26 {2019}
https://www.practiceupdate.com/C/88648/56?elsca1=emc_enews_topic-alert
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A PoEM on breast cancer metastasis [newly identified macrophage induces metastasis]
When breast cancer cells spread through the body, they do so mainly through the lymph system that normally removes excess fluid and waste products from our tissues. Now, scientists from the group of Professor Massimiliano Mazzone (VIB-KU Leuven Center for Cancer Biology) identified a novel subset of immune cells, called Podoplanin-expressing macrophages (PoEMs), that change the tissues near a tumor in a way that promotes the spreading of cancer cells. Getting rid of these PoEMs in a mouse model strongly reduced the ability of breast cancer cells to move to other parts of the body...
These findings provide supportive evidence to targeting PoEMs in humans. With the help of clinicians and pathologists from KU Leuven and UZ Antwerpen, the researchers further tested their findings in human cancer samples. Pawel Bieniasz-Krzywiec provides more details: "On top of the mice results, human breast cancer sample testing revealed a positive correlation between the presence of PoEMs around tumor lymph vessels and lymph node involvement as well as organ metastasis. These observations pave the road towards the use of PoEM blockers in cancer therapy, specifically targeting the cancer-associated lymphatic vessels, without triggering lymphedema associated with current strategies."
Article: https://medicalxpress.com/news/2019-08-poem-breast-cancer-metastasis.html
Study: https://www.sciencedirect.com/science/article/abs/pii/S1550413119304280?via%3Dihub
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Turbocharging the body's natural killer cells to defeat cancer
The scientists found that a protein -- called Activin-A -- which is found naturally in both healthy human cells and cancer cells, directly disables the NK cell's capacity to halt cancer growth.
Importantly, they were able to block Activin-A in preclinical models, using human and mouse NK cell models, with the hormone Follistatin.
According to Professor Huntington, "these findings may open the door to novel immune-therapy drugs which provide a deeper and more durable way to overcome the immune suppression seen in cancer, improving patient outcomes."
Mentioned in the study:
In breast and ovarian cancer cells, activin-A signaling induces the epithelial-mesenchymal transition (EMT), a malignant cellular reprogramming that is characteristic of TGF-β signaling (28, 29). In addition, activin-related genes are increased in expression during breast cancer cell EMT (30).
Article: https://www.sciencedaily.com/releases/2019/08/190827145734.htm
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Lumpie, The FDA encouraging men to be included in trials and studies is a huge thing.
Here's another link to an article that quotes my view:
https://www.forbes.com/sites/victoriaforster/2019/...
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High Marks for Proton-Beam RT in Breast Cancer
No grade 3 radiation toxicity, good disease control and survival at 5 years
Women with locally advanced breast cancer requiring regional lymph node irradiation had similar disease control with less toxicity with proton-beam radiation therapy (RT) as compared with historical patients treated with conventional radiotherapy, investigators in a small prospective study reported.
PURPOSE
To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation.
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://ascopubs.org/doi/abs/10.1200/JCO.18.02366?journalCode=jco
DOI: 10.1200/JCO.18.02366 Journal of Clinical Oncology
Published online August 26, 2019.
{Mysticalcity: how funny. We seem to have been reading the same article at the same time!}
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Pyrotinib or Lapatinib Combined With Capecitabine in HER2–Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study
PURPOSE
Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study.
CONCLUSION
In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
https://ascopubs.org/doi/abs/10.1200/JCO.19.00108
DOI: 10.1200/JCO.19.00108 Journal of Clinical Oncology
Published online August 20, 2019.
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Regarding proton beam therapy, I was just reading an article a few days ago about carbon ion therapy, which was initiated in the U.S. but is now available only in Asia and Europe.
"Carbon ion therapy is similarly precise [to proton therapy], but because carbon ions are heavier, they deliver more cancer-killing power than protons do. Carbon centers have reported impressive survival rates, particularly for hard-to-treat bone and soft-tissue cancers such as spinal tumors."
https://www.wired.com/story/why-a-promising-potent-cancer-therapy-isnt-used-in-the-us/
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Hormone Therapy and Breast Cancer: Yes, There Is Risk
But how big, and how important for individual women, is thornier question
Menopausal hormone therapy (MHT) was tied to increased breast cancer risk in a global study -- but implications for individual patients are less clear.
...those who reported ever using MHT had a 26% higher relative risk for developing breast cancer compared with never-users (RR 1.26, 95% CI 1.24-1.28), reported the Collaborative Group on Hormonal Factors in Breast Cancer.
the findings are definitely concerning, ... "Clinicians must heed the message of this study but also take a rational and comprehensive approach to the management of menopausal symptoms, with careful consideration of the risks and benefits of initiating MHT for each woman."
"This might be dependent on severity of the symptoms, contraindications for MHT (i.e., breast cancer, cardiovascular disease, and stroke), and BMI, and could take into account patient preference," she continued. "For likely candidates, MHT (preferably estrogen alone) should be initiated around the time of natural menopause and ideally limited to 5 years of use."
Primary Source
The Lancet
Source Reference: Collaborative Group on Hormonal Factors in Breast Cancer "Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence" Lancet 2019; DOI: 10.1016/S0140-6736(19)31709-X.Secondary Source
The Lancet
Source Reference: Kotsopoulos J "Menopausal hormones: definitive evidence for breast cancer" Lancet 2019; DOI: 10.1016/S0140-6736(19)31901-4.
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Positive Breast Cancer Data for PD-1/L1 Inhibitors
Higher pCR rate in neoadjuvant setting follows success in metastatic triple-negative disease
Adding a PD-L1 inhibitor to neoadjuvant chemotherapy increased the rate of pathologic complete response (pCR) in triple-negative breast cancer (TNBC), particularly when the immunotherapy was started first, a placebo-controlled trial showed.
Patients who received durvalumab (Imfinzi) in addition to chemotherapy had a pCR rate of 53.4% versus 44.2% with placebo and chemotherapy. The difference did not attain statistical significance, except in a subgroup of patients who started the PD-L1 inhibitor 2 weeks before chemotherapy. In that subgroup, the odds of achieving pCR more than doubled with durvalumab.
The results added to evidence from a previous study that showed significant improvement in pCR with the addition of pembrolizumab (Keytruda) to chemotherapy for patients with newly diagnosed TNBC.
"We now have an approved indication in breast cancer, and I think that represents real progress,"
Primary Source
Annals of Oncology
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New clues to the cause of permanent hair loss caused by chemotherapy.
Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy
The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy.
https://www.nature.com/articles/s41467-019-11665-0
- Published: 27 August 2019
- Nature Communicationsvolume 10, Article number: 3694 (2019)
{This article is extremely technical but the matter will undoubtedly be of interest to some.}0 -
Trastuzumab Biosimilar vs Reference Trastuzumab in the Neoadjuvant Setting for HER2-Positive Breast Cancer
- The authors of this report provide 3-year follow-up data from a phase III study of a trastuzumab biosimilar versus reference trastuzumab in the neoadjuvant management of HER2+ breast cancer. Cardiotoxicity was rare, with similar rates between groups. The 3-year event-free survival was better in the biosimilar group compared with the reference trastuzumab group (91.9% vs 85.2%).
- The rate of event-free survival at 3 years was better with a trastuzumab biosimilar than with reference trastuzumab, and cardiotoxicity was rare in both cohorts.
{It has been noted that this study investigated only one of 5 available biosimilars; nonetheless, it may be reassuring to some that biosimilars are not simply inferior.}0
