Breaking Research News from sources other than Breastcancer.org
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Sharing this post from Best Bird's website:
Trastuzumab Deruxtecan (DS-8201) is a novel drug consisting of a HER2 antibody attached to a "topoisomerase I inhibitor" (a new class of anticancer agents that interrupt DNA replication in cancer cells).
The recent Phase 2 DESTINY BreastO1 clinical trial studied trastuzumab deruxtecan in 115 patients with unresectable and/or metastatic cancer who had previously received a median 7 lines of therapy including Herceptin and Kadcyla (as well as Perjeta in most cases). The patients in the study had either: HER2-positive breast cancer, HER2–low expressing breast cancer (considered HER2 negative), HER2-positive gastric cancer, or various other HER2-expressing solid tumors. Data revealed that the overall response rate with trastuzumab deruxtecan was 59.5% and the disease control rate was an impressive 93.7%. The median duration of response was 20.7 months, the median progression-free survival was 22.1 months, and the median overall survival has not yet been reached. From: https://www.targetedonc.com/news/fam-trastuzumab-deruxtecan-demonstrates-encouraging-responses-in-advanced-her2-breast-cancer As of May 2019, there are three recruiting clinical trials of trastuzumab deruxtecan for MBC patients.
You can find Best Bird's web site at www.insidersguidembc.com. It is an excellent resource. Her ebook is available in multiple formats for a small charge, in PDF format free of charge. It is also available in print form.
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Mammo-Based Deep Learning Model Assesses Breast Cancer Risk
Deep learning models more accurate than models that use traditional risk factors, breast density
THURSDAY, May 9, 2019 (HealthDay News) -- Mammography-based deep learning (DL) breast cancer risk models are more accurate than models that consider traditional risk factors and breast density, according to a study published online May 7 in Radiology.
Adam Yala, from Massachusetts Institute of Technology in Cambridge, and colleagues conducted a retrospective study involving 39,751 women with 88,994 consecutive screening mammograms to develop a mammography-based DL breast cancer risk model. For each patient, all examinations were assigned to training (71,689 examinations), validation (8,554 examinations), or test set (8,751 examinations). Three models were developed to assess breast cancer risk within five years: a risk factor-based logistic regression model (RF-LR) that included traditional risk factors, a DL model (image-only DL) that used mammograms alone, and a hybrid model combining traditional risk factors and mammograms.
The researchers included 3,937 women in the test set. The areas under the receiver operating characteristics curve (AUCs) were 0.70 and 0.68 for the hybrid DL and image-only DL, respectively. The AUCs for RF-LR and a comparison model that included breast density (Tyrer-Cuzick [TC] model) were 0.67 and 0.62, respectively. Compared with the TC and RF-LR models, the AUC for hybrid DL was significantly higher.
"These results support the hypothesis that mammography contains informative indicators of risk not captured by traditional risk factors, and DL models can deduce these patterns from the data," the authors write. "These models have the potential to replace conventional risk prediction models."
Massachusetts Institute of Technology and Massachusetts General Hospital have filed patents on the deep learning models.
https://www.practiceupdate.com/C/83470/56?elsca1=emc_enews_topic-alert
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The Impact of Chest Wall Boost on Reconstruction Complications and Local Control in Patients Treated for Breast Cancer
- International Journal of Radiation Oncology*Biology*Physics The authors of this study performed a retrospective chart review of 746 breast cancer patients to evaluate whether delivery of a chest wall boost (CWB) to the mastectomy scar/chest wall is independently associated with reconstruction complications. Upon multivariate analysis, the authors found that CWB was significantly associated with infection, skin necrosis, and implant exposure. Among patients receiving implant reconstruction, CWB was independently associated with increased risk of implant failure.Based on these findings, the study authors conclude that omission of CWB in post-mastectomy radiation may improve breast reconstruction outcomes without a deleterious effect on local tumor control.
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Resistance Mechanisms to Anti-HER2 Therapies in HER2-Positive Breast Cancer
- Critical Reviews in Oncology / Hematology The authors of this review highlight current knowledge regarding the mechanisms involved in the development of anti-HER2 therapy resistance in HER2-positive breast cancer.The authors provide detail on mechanisms such as impaired drug binding to HER2, constitutive and self-sufficient signaling in HER-related signaling pathways, metabolic reprograming, and attenuation of the immune system activation state.
Abstract:HER2-positive breast cancer (HER2 + BC) represents 15–20% of all BCs. In the last two decades, the introduction of monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs) directed against HER2 impressively improved patient prognosis in all disease stages.Yet, not all patients with limited-stage disease are cured, and HER2+ metastatic BC (mBC) remains an almost invariably deadly disease. Primary or acquired resistance to anti-HER2 therapies is responsible for most treatment failures. In recent years, several resistance mechanisms have been identified, such as impaired drug binding to HER2, constitutive activation of signaling pathways parallel or downstream of HER2, metabolic reprogramming or reduced immune system activation. However, only a few of them have been validated in clinical series; moreover, in the era of standard-of-care dual HER2 blockade, these mechanisms should be re-assessed and, in case, confirmed with anti-HER2 combinations.Defining the best strategies to delay or revert resistance to anti-HER2 treatments will be crucial to improve their clinical efficacy.https://www.practiceupdate.com/C/83253/56?elsca1=emc_enews_topic-alerthttps://www.sciencedirect.com/science/article/pii/S1040842818304463https://doi.org/10.1016/j.critrevonc.2019.05.001{At present, there is a charge for access tot he full article unless you have access to a research library.}0 -
Less Invasive Mastectomy an Option for More Patients
Higher-risk patients may now be eligible for nipple-sparing mastectomy
WEDNESDAY, May 8, 2019 (HealthDay News) -- Complication rates for nipple-sparing mastectomy (NSM) are decreasing despite expanded indications for the procedure among higher-risk patients, according to a study presented at the annual meeting of the American Society of Breast Surgeons, held from April 30 to May 5 in Dallas.
Whitney Young, M.D., from the Mayo Clinic in Rochester, Minnesota, and colleagues examined complication and reconstruction success rates among patients treated in 2009 to 2017 with NSM identified from an institutional, prospective breast surgery registry. Analysis included 1,301 breasts in 769 women undergoing NSM for cancer or risk reduction (median age, 48 years).
The researchers found that the overall 30-day complication rate was 7.5 percent but declined from 14.8 percent in 2009 to 6.3 percent in 2017. During the same time period, the proportion of patients with obesity and treated with neoadjuvant chemotherapy increased. There was a significant increase in 30-day complication rates among patients with prior radiation (odds ratio, 2.3) and recent/current smoking (odds ratio, 3.3). At one year, reconstruction success was 98.5 percent. One-year reconstruction failure was significantly associated with previous radiation (odds ratio, 4.6) and postoperative adjuvant radiation (odds ratio, 3.3).
"These data confirm a team learning curve with NSM and also demonstrate the nipple-sparing approach is suitable for appropriately selected higher-risk patients for both risk reduction and cancer treatment," the authors write.
https://www.practiceupdate.com/C/83453/56?elsca1=emc_enews_topic-alert
https://www.breastsurgeons.org/meeting/2019/press_releases/nipple_sparing.php
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Detailed Phenotyping and Distinct Trajectories of Cardiovascular Function and Symptoms With Exposure to Modern Breast Cancer Therapy
- Journal: Cancer
- Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership.
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New Lesions ID'd on Breast MRI During Treatment Likely Benign
New suspicious lesions detected on breast MRI during neoadjuvant therapy are more likely benign
For patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer, magnetic resonance imaging (MRI) examinations with new suspicious findings are unlikely to represent a new site of malignancy, according to a study presented at the annual meeting of the American Roentgen Ray Society, held from May 5 to 10 in Honolulu.
Donna Eckstein, M.D., from the University of California in San Francisco, and colleagues identified all breast MRI examinations performed to assess response to neoadjuvant chemotherapy from 2000 to 2018. Study cases classified as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 were identified. All cases with new suspicious lesions found after initiation of neoadjuvant treatment were included; 28 MRI examinations were included.
The researchers found that all study cases were identified as BI-RADS 4. Sixteen lesions were contralateral to known malignancy, while 11 and one were ipsilateral and bilateral, respectively. Lesions included mass, nonmass enhancement, and focus (18, eight, and two, respectively). Twenty-five of the cases had tissue diagnosis or sufficient imaging follow-up to establish diagnosis; the outcomes were unknown in three cases. In cases with known outcomes, none of the new suspicious findings were malignant, while 11, five, and nine were proven benign at percutaneous biopsy, proven benign at surgical pathology, and presumed benign after resolution of the suspicious lesions or stability over more than two years, respectively.
"Our findings suggest that new suspicious findings on MRI arising during neoadjuvant therapy are almost certainly benign, although larger studies across facilities are needed to confirm whether biopsy may be safely averted in these scenarios," the authors write.
https://www.practiceupdate.com/C/83394/56?elsca1=emc_enews_topic-alert
https://cf.arrs.org/abstracts/oralpresentations/index.cfm?fid=2406
Abstracts 1913-2417
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Trastuzumab Deruxtecan in Advanced HER2+ Breast Cancer Previously Treated With Trastuzumab Emtansine
- The Lancet Oncology - Published:April 29, 2019
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Impact of Lymphoscintigraphy as Part of Sentinel Node Biopsy in Early Breast Cancer
- Journal of Clinical Oncology
- The aim of the current work was to clarify whether a preoperative lymphoscintigraphy (LSG) enhances staging accuracy of sentinel lymph node biopsy (SLNB).
DOI: 10.1200/JCO.18.02092 Journal of Clinical OncologyNote: Lymphoscintigraphy (sentinel lymph node mapping) is an imaging technique that is used to identify the lymph drainage basin, determine the number of sentinel nodes, differentiate sentinel nodes from subsequent nodes, locate the sentinel node in an unexpected location, and mark the sentinel node over the skin for biopsy.0 -
WOW on a roll Lumpie.. many thanks
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I had gotten behind and have been trying to catch up.
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https://www.medpagetoday.com/hematologyoncology/br...
Adjuvant Denosumab Improved DFS in HR+ Breast Ca
"Combining an every-6-month dose of the osteoporosis medication denosumab (Prolia, Xgeva) with standard adjuvant aromatase-inhibitor treatment significantly delayed disease recurrence in postmenopausal women with hormone receptor-positive breast cancer, according to updated results of the ABCSG-18 trial."
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https://www.medpagetoday.com/hematologyoncology/br...
Adjuvant Denosumab Improved DFS in HR+ Breast Ca
"Combining an every-6-month dose of the osteoporosis medication denosumab (Prolia, Xgeva) with standard adjuvant aromatase-inhibitor treatment significantly delayed disease recurrence in postmenopausal women with hormone receptor-positive breast cancer, according to updated results of the ABCSG-18 trial.
At 8 years of follow-up, women randomly assigned to denosumab had about a three percentage-point difference in absolute disease-free survival compared with those who received placebo (80.6% vs 77.5%), Michael Gnant, MD, of Medical University of Austria in Vienna, and colleagues reported."
Sources listed in medpage today (see below)
Primary Source
Lancet Oncology
Source Reference: Gnant M, et al "Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomized, double-blind, placebo-controlled, phase 3 trial" Lancet Oncol 2019; DOI: 10.1016/S1470-2045(18)30862-3.Secondary Source
Lancet Oncology
Source Reference: Lippman M "Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer" Lancet Oncol 2019; DOI: 10.1016/S1470-2045(18)30913-6.
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Not a scientific journal, none the less interesting: "..opens up the prospect of long-term control with a good quality of life." https://www.theguardian.com/science/2019/may/16/new-war-on-cancer-aims-at-longterm-survival-not-cure
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Perspectives on Conversations About Costs of Cancer Care of Breast Cancer Survivors and Cancer Center Staff: A Qualitative Study
With the cost of cancer care, and health care in general, there is more and more discussion about the importance of providers having cost of care conversations with patients.
However, as this article highlights, "little formal guidance is available on how to conduct these sensitive conversations in ways that are acceptable to both patients and providers." It is an important step that everyone involved is open to having these critical conversations, but now we need to figure out the actual steps to do so that is best for everyone.DOI: 10.7326/M18-2117
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Hormone Therapy in Transgender Women Ups Breast Cancer Risk
Transgender women receiving hormone treatments are at greater risk for developing breast cancer than cisgender men, according to a study published online May 15 in The BMJ. {Researchers} retrospectively performed an observational study of transgender women and men who received gender-affirming hormone treatment between the years of 1972 and 2016. Transgender women received a combination of antiandrogens and estrogens for an average duration of 13 years, with treatments beginning at a median age of about 31 years. Transgender men underwent testosterone treatments for an average of eight years, beginning at a median age of 23 years. The incidence and characteristics of breast cancer were compared for those in the cohort and the general population. The researchers identified 18 cases of breast cancer (15 invasive and three noninvasive) in 17 of the 2,260 transgender women after an average of 18 years of hormone treatment. The average age at diagnosis was 50 years. Compared with cisgender men, transgender women had a 46-fold higher risk for breast cancer (standardized incidence ratio [SIR], 46.7); however, this risk was lower than that seen in cisgender women (SIR, 0.3). The majority of these cases were found to be ductal in origin and estrogen and progesterone receptor-positive; 8.3 percent were human epidermal growth factor receptor 2-positive. Invasive breast cancer was diagnosed in four of the 1,229 transgender men (no noninvasive cases were reported), with diagnosis occurring at an average age of 47 years after a median of 15 years of hormone treatment. Compared with cisgender women, this number was lower than expected (SIR, 0.2). This research "suggests that hormone treatment alters the risk of breast cancer in transgender people compared with initial risk based on their birth assigned sex," the authors write.
News report: https://www.practiceupdate.com/C/83943/56?elsca1=emc_enews_topic-alert
Juournal article: https://www.bmj.com/content/365/bmj.l1652
doi: https://doi.org/10.1136/bmj.l1652 (Published 14 May 2019)
{I have not seen a lot of research specific to breast cancer and transgender men and women so I wanted to make a point to share this reference.}
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Perhaps good news for those of us on Tamoxifen and Antidepressants such as Cymbalta. My MO brought this new study to my attention at our appt yesterday.
https://www.ncbi.nlm.nih.gov/pubmed/30542984CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy
PURPOSE:
Tamoxifen is widely used to reduce the risk of breast cancer (BC) recurrence and extend disease-free survival among women with estrogen-sensitive breast cancers. Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen.
METHODS:
The present cohort study of 960 women diagnosed with early-stage BC between 1993 and 1999 examined the association between concomitant use of CYP2D6 inhibitors and adjuvant tamoxifen and the risk of adverse BC outcomes (recurrence, second primary BC, BC mortality), both overall and according to CYP2D6 metabolic phenotype.
RESULTS:
Six or more months of CYP2D6 inhibitor use concomitant with tamoxifen was not associated with any appreciable increase in risk of recurrence or second primary BC or BC mortality, and there was no clear evidence of variation by CYP2D6 metabolic phenotype.
CONCLUSIONS:
These results are consistent with the relatively few other large, population-based studies conducted to date that have not observed an increased risk of adverse BC outcomes associated with CYP2D6 inhibition.
KEYWORDS:
Breast cancer; CYP2D6; Pharmacogenetics; Survival; Tamoxifen
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A Rare Genetic Mutation Leads to Cancer. The Fix May Already Be in the Drugstore (NYT Article)
Study: https://science.sciencemag.org/content/364/6441/eaau0159
"In a study published on Thursday in the journal Science, researchers found evidence that a compound called indole-3-carbinol (i3c) blocks an enzyme that inhibits the activity of Pten. With the gene more active, patients with the mutation may be better protected against cancer."
"The mutation is not just inherited; the Pten gene is spontaneously mutated in many tumors. When that happens, the patient's prognosis is poor."
"The gene governs production of an enzyme that stops cells from dividing too quickly, reducing the chances that cancers will form. With reduced activity in Pten, cells grow uncontrollably.Pten mutations do not completely halt the gene's functions. Instead, the mutations tamp down the gene's activity, so cells make less of the enzyme needed for orderly growth.
But one of the hardest things for researchers to do is to find a way to increase, rather than turn off, a gene's activity. Eventually, Dr. Pandolfi and his colleagues learned enough about the Pten system to reason that i3c might do the trick.
"We got lucky, or smart," he said.
Dr. Pandolfi and his colleagues tested their treatment on human prostate cancer cells and in mice bred to develop prostate cancer. It worked: In the cells and in mice, i3c treatment resulted in fewer cancers, and those that arose were small and less deadly."
Keywords: DIM Supplement, i3c, Indole-3-Carbinol
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Also, there is this new breaking news...
A Rare Genetic Mutation Leads to Cancer. The Fix May Already Be in the Drugstore (NYT Article)
Study: https://science.sciencemag.org/content/364/6441/eaau0159
"In a study published on Thursday in the journal Science, researchers found evidence that a compound called indole-3-carbinol (i3c) blocks an enzyme that inhibits the activity of Pten. With the gene more active, patients with the mutation may be better protected against cancer."
"The mutation is not just inherited; the Pten gene is spontaneously mutated in many tumors. When that happens, the patient's prognosis is poor."
"The gene governs production of an enzyme that stops cells from dividing too quickly, reducing the chances that cancers will form. With reduced activity in Pten, cells grow uncontrollably.Pten mutations do not completely halt the gene's functions. Instead, the mutations tamp down the gene's activity, so cells make less of the enzyme needed for orderly growth.
But one of the hardest things for researchers to do is to find a way to increase, rather than turn off, a gene's activity. Eventually, Dr. Pandolfi and his colleagues learned enough about the Pten system to reason that i3c might do the trick.
"We got lucky, or smart," he said.
Dr. Pandolfi and his colleagues tested their treatment on human prostate cancer cells and in mice bred to develop prostate cancer. It worked: In the cells and in mice, i3c treatment resulted in fewer cancers, and those that arose were small and less deadly."
Keywords: DIM Supplement, i3c, Indole-3-Carbinol
Glad to hear that one of the supplements I'm taking is DIM. Fingers crossed.0 -
First U.S. use of CRISPR to directly target cancer will seek go-ahead from regulators
If all goes as planned, the first clinical trial in the United States testing CRISPR against cancer by altering the DNA of tumor cells inside patients could begin recruiting participants next year, the scientist leading the effort told STAT.
The Gene Editing Institute....is preparing to seek regulatory approval for a much bolder CRISPR cancer study. If it receives the OK from the Food and Drug Administration, which it plans to request in the next few months, it would recruit six to 10 patients with late stage non-small-cell lung cancer and test whether using CRISPR to disable a particular gene would allow standard chemotherapy to work better and longer, ideally buying patients a little more time. "The goal is to give them a few more months of life, but we hope there will be additional benefits."
His target: a gene called NRF2 (nuclear factor erythroid 2-related factor). It produces a protein called a transcription factor, which activates some 200 genes that, among other things, pump alien chemicals out of tumor cells. Those chemicals include the chemotherapy drugs cisplatin and carboplatin, so lung cancer cells become resistant to them. "NRF2 is a major culprit in fighting off cisplatin and carboplatin," Kmiec said. "And expression of NRF2 increases as lung cancer goes from stage 1 to 2 to 3 to 4," advancing first to the lymph nodes and then to distant organs. "We thought it would make a good target."
One reason to believe the edit will hit its target and nothing else is that cells with high expression of NRF2 have a little chunk of DNA that serves as a roadside beacon for CRISPR. Healthy cells lack it. Called a PAM sequence, it should ensure that CRISPR disables NRF2 only in tumor cells and not normal ones.
Because the trial will recruit patients with lung cancer so advanced (stage 3 or 4) they have at most six months to live, Kmiec hopes that regulators will demand fewer guarantees of safety. For instance, there have been concerns that CRISPR'd cells might be prone to developing new cancers decades hence. But that might not be relevant to patients with almost no chance to live that long. Exactly what safety assurances the FDA will require, however, is unclear.
"I think we'll be underway in 18 months," Kmiec said, "but it might be earlier."
{Site may require a sign in but there is not a fee for access.}
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'I want to live': Women share realities of living with terminal breast cancer, raise money to eradicate the disease
POSTED 6:54 AM, MAY 24, 2019, BY STACEY FREY, UPDATED AT 08:41AM, MAY 24, 2019
Not research, but some of you may be interested in seeing this news report on a group of women in the Cleveland, Ohio, area supporting one another through MBC. Nice to get some coverage of MBC! They have a fundraiser coming up. There's a link in the print report.
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Liquid biopsy could identify cancer patients at risk of metastatic disease, offering an opportunity to tailor treatment
Analysing fragments of DNA that are shed by tumours into the bloodstream, could indicate early on whether patients are at risk of their cancer spreading, according to new research presented today.
16 May 2019
Researchers at The Royal Marsden say ctDNA, a form of liquid biopsy, may be an accurate technique to monitor treatment response in patients with locally advanced rectal cancer, allowing treatment to be adapted or changed earlier to try to prevent the development of metastatic disease.
"Importantly what this study showed, which has not yet been explored, is that persistence of ctDNA mid-way through treatment could be an early indicator of the cancer's potential to spread. Using this measure, along with MRI scans, we can offer a more personalised treatment approach for patients." "Whilst our findings are interesting and exciting, it's important to note that this was carried out in a small cohort of patients and would require further validation in a larger trial."
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New method of breast reconstruction may reduce pain for some cancer survivors
NOVEMBER 21, 2018
But in recent years...surgeons have found a way to keep the implant on top of the muscle and address those problems: they're surrounding the implants with a biologic mesh, essentially a thin layer of collagen.
"Now we can put the implants under the skin and a subsequent next layer of biologic mesh to protect the implant – so the implants are not right under skin, so the implants are sitting under a layer of mesh, in a pocket we've created using the mesh," said Sbitany. "In essence, we have the ability to do a totally muscle-sparing, muscle-preserving breast reconstruction."
The fat grafting helps to be able to add protection around the implant and better contour the shape of the new breast, he said.
we've found this is a very safe option in the setting of radiation," said Sbitany.
Another benefit of avoiding dissecting the pectoral muscle is a substantial reduction in pain.
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Surveillance After Treatment of Localized Breast Cancer: Time for Reappraisal?
https://www.medscape.com/viewarticle/912080?src=wnl_edit_tpal&uac=153476CT&impID=1974273&faf=1
The lead author, Joseph Sparano, is a highly respected figure in breast cancer research and probably familiar to many of you. It seems to me that if he's discussing this topic there is hope that it will arouse interest in the wider oncology community sooner rather than later.
(You may need to register to read the article but it's free and non-intrusive.)
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Seems we can’t access this link Lumpie, but appreciate the effort! Kare
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Is it better to 'contain' rather than destroy cancer?
A recent study in mice has found that an existing drug could effectively contain metastatic breast cancer cells.
Existing drug can block stray cancer cells
The researchers zeroed in on the drug fostamatinib, which is currently approved for the treatment of immune thrombocytopenia, an autoimmune disease characterized by a low platelet count in the blood.
The team explains that their research in mice has shown that fostamatinib is also able to contain metastatic cancer cells and stop them from developing into full tumors, causing further damage.
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Thanks for posting, mysticalcity. That was at once both hopeful and terrifying!
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First-in-Class Treatment Approved for Advanced Breast Cancer
https://www.empr.com/home/news/first-in-class-trea...0
