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Topic: Breaking Research News from sources other than Breastcancer.org

Forum: Clinical Trials, Research News, Podcasts, and Study Results —

Share your research articles, interpretations and experiences here. Let us know how these studies affect you and your decisions.

Posted on: Nov 20, 2017 11:31PM - edited Nov 20, 2017 11:35PM by Lumpie

Lumpie wrote:

I watch for research news on breast cancer, treatments, etc., and frequently see interesting articles. There is a topic on BCO called "Breaking Research News from Breastcancer.org." One of the moderators suggested that another topic might be appropriate for posting links and synopses of reports on research found elsewhere. So here it is! Please post links to reports on research form reliable sources. Thanks for sharing!

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 14, 2018 12:29PM marijen wrote:

Scientists have linked 110 genes to an increased risk of breast cancer in the most comprehensive study ever to unpick the genetics of the disease.

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Their study used a pioneering genetic technique to analyse maps of DNA regions linked to an inherited risk of breast cancer and identify the actual genes involved in raising a woman's risk.

Researchers also linked 32 of the new genes to the length of time women survived breast cancer -- suggesting these could be important in the development of the disease and potential targets for future treatments.

Scientists at The Institute of Cancer Research, London, looked in detail at 63 areas of the genome that had previously been associated with the risk of breast cancer by mapping studies.

Finding the genes responsible for the increased risk is not straightforward because small sequences of DNA can interact with completely different parts of the genome through a strange phenomenon known as 'DNA looping'.

But the researchers, funded by Breast Cancer Now, used a technique they developed called Capture Hi-C to study interactions between different regions of the genome.

The study -- published today (Monday) in Nature Communications -- uncovered which specific genes were involved and how that might increase a woman's risk of developing breast cancer.

The team at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) found that some of the 63 regions of the genome were physically interacting with genes more than a million letters of DNA code away.

They were able to identify 110 new genes that could potentially be causing an increased risk of breast cancer across 33 of the regions they studied. In the remaining 30 areas, they were unable to find any specific genes.

One third of the target genes for which they had patient data -- 32 out of 97 -- were also linked to survival in women with oestrogen receptor-positive breast cancer, suggesting they play an important role in the disease.

In the future, testing for these genes could help pick out women who are most at risk of developing the disease -- or they could be explored as targets for new drugs.

Scientists at the ICR -- a research institute and charity -- studied DNA loops in cells from four different types of breast cancer and normal, healthy cells to find out which genes were consistently involved in looping interactions.

Most of the 110 genes found in the study had not been linked to breast cancer risk before, and further work will be needed to determine the extent of their role in the disease.

One of these, called FADD, has previously been linked to head and neck cancer and lung cancer and could be a promising target for new cancer therapies.

Previous large-scale genetics studies have implicated 14 of the 110 genes as playing a role in breast cancer risk, such as the oestrogen receptor gene ESR1, showing that Capture Hi-C is an effective tool for picking up risk genes.

Dr Olivia Fletcher, Team Leader in Functional Genetic Epidemiology at The Institute of Cancer Research, London, said: "Our study took the high-level maps of breast cancer risk regions and used them to pull out specific genes that seem to be associated with the disease.

"We studied how DNA forms loops to allow physical interactions between a DNA sequence in one part of the genome and a risk gene in another.

"Identifying these new genes will help us to understand in much greater detail the genetics of breast cancer risk. Ultimately, our study could pave the way for new genetic tests to predict a woman's risk, or new types of targeted treatment."

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which funded the study, said: "These are really important findings. We urgently need to unravel how the genetic changes in the building blocks of our DNA influence a woman's risk of breast cancer, and this study adds another vital piece to this jigsaw.

"More women are now being diagnosed with breast cancer than ever before, and these crucial findings could ultimately help us more accurately predict who is most at risk and develop new targeted treatments.

"Many of these genes have been relatively undocumented to date and we now hope further research will untangle their exact role in breast cancer risk, and how we could use them to stop more women developing the disease."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: "Large-scale genomic studies have been instrumental in associating areas of our DNA with an increased risk of breast cancer. This study brings these regions of DNA into sharper focus, uncovering a treasure trove of genes that can now be investigated in more detail.

"The ways in which particular genes influence cancer risk are highly complex. In the future, a better understanding of the genes identified in this study could lead to the discovery of new targeted drugs, or new strategies to improve diagnosis or prevention of the disease."


Story Source:

Materials provided by Institute of Cancer Research. Note: Content may be edited for style and length.

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Mar 14, 2018 12:36PM marijen wrote:

Protein keeps metastatic breast cancer cells dormant: Research reveals one of the mechanisms that allows metastatic cells to leave a latent state
https://www.sciencedaily.com/releases/2018/01/180122150822.htm



A recent study has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light on the molecular basis underlying how the expression of certain genes facilitates the spread of metastatic lesions.

www.sciencedaily.com


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Mar 14, 2018 03:00PM Amelia01 wrote:

Dyes may help identify hidden cancer cells:


https://www.newsmax.com/Health/health-news/glowing...

Dx 10/17/2017, ILC/IDC, Left, 6cm+, 17/21 nodes, ER+/PR+, HER2- Surgery 11/6/2017 Chemotherapy Cytoxan (cyclophosphamide), Ellence (epirubicin), Taxol (paclitaxel)
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Mar 14, 2018 04:11PM LaurenH wrote:

So much exciting stuff coming! They just need to go FASTER!!

Dx 12/2002, IDC, Right, 1cm, Stage IIA, Grade 3, 1/23 nodes, ER+/PR+, HER2+ (FISH) Dx 2/15/2018, IDC, Left, Stage IV, ER+/PR-, HER2+ Targeted Therapy 2/21/2018 Herceptin (trastuzumab) Targeted Therapy 2/23/2018 Ibrance (palbociclib) Radiation Therapy 3/1/2018 External: Bone Hormonal Therapy Arimidex (anastrozole) Targeted Therapy Herceptin (trastuzumab) Chemotherapy AC + T (Taxotere) Surgery Lumpectomy: Right; Lymph node removal: Right, Sentinel, Underarm/Axillary Radiation Therapy Whole-breast: Breast, Lymph nodes Hormonal Therapy Faslodex (fulvestrant)
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Mar 14, 2018 04:26PM Dianarose wrote:

Lauren- I agree. Seems like every article says,’ in the future ‘ . So frustrating

6/10/13 mets to ovary now. Now mets. To peritoneal stage IV Dx 3/22/2012, ILC, Both breasts, 1cm, Stage IV, metastasized to bone/other, Grade 2, 17/17 nodes, ER+/PR+, HER2- Chemotherapy 5/31/2012 CMF Radiation Therapy 12/3/2012 3DCRT: Breast, Lymph nodes Hormonal Therapy 8/10/2013 Aromasin (exemestane) Targeted Therapy
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Mar 16, 2018 05:22AM LaurenH wrote:

http://www.onclive.com/web-exclusives/acquired-her2-mutations-cause-endocrine-resistance-in-er-breast-cancer

Dx 12/2002, IDC, Right, 1cm, Stage IIA, Grade 3, 1/23 nodes, ER+/PR+, HER2+ (FISH) Dx 2/15/2018, IDC, Left, Stage IV, ER+/PR-, HER2+ Targeted Therapy 2/21/2018 Herceptin (trastuzumab) Targeted Therapy 2/23/2018 Ibrance (palbociclib) Radiation Therapy 3/1/2018 External: Bone Hormonal Therapy Arimidex (anastrozole) Targeted Therapy Herceptin (trastuzumab) Chemotherapy AC + T (Taxotere) Surgery Lumpectomy: Right; Lymph node removal: Right, Sentinel, Underarm/Axillary Radiation Therapy Whole-breast: Breast, Lymph nodes Hormonal Therapy Faslodex (fulvestrant)
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Mar 16, 2018 04:32PM marijen wrote:

I still have pain after surgery - didn’t know this...

The Titanium Marker in Breast Biopsy: Should You Worry?

Is it possible to have an adverse reaction to a titanium marker placed in a breast biopsy? Here's what you should know.

PJ Hamel

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Mar 16, 2018 06:00PM 7of9 wrote:

I find the notion of not removing cancerous lymph nodes to be scary. I had extracapsular extension and there is no way those lymph nodes were doing their jobs anymore...so out they had to go. Good riddance!

If you're going through hell, keep on going. You might get out before the devil even knows you're there. Dx 1/18/2012, IDC, Left, 2cm, Stage IIB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 5/31/2012 Lymph node removal: Left; Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 10/31/2012 Reconstruction (left); Reconstruction (right) Dx 12/23/2015, IDC, Left, 2cm, Grade 2, 10/14 nodes, ER+/PR+, HER2- Surgery 1/18/2016 Lymph node removal: Left, Underarm/Axillary Surgery 1/18/2016 Prophylactic ovary removal Radiation Therapy 2/10/2016 Whole-breast: Breast, Lymph nodes, Chest wall Chemotherapy 3/31/2016 Taxotere (docetaxel) Hormonal Therapy Arimidex (anastrozole)
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Mar 17, 2018 11:57AM NotBrokenJustBent wrote:

7of9, I would tend to agree. If nodes can be treated by chemo and radiation alone then why can't smallish tumors be treated the same instead of disfiguring mx and lumpectomies?

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Mar 18, 2018 05:32AM marijen wrote:

ASCO Reading Room 01.02.2018Comment

Research Update: Locoregional Recurrence After Breast Cancer Treatment Subtype, nodal status, and receptor status all influence risk
https://www.medpagetoday.com/reading-room/asco/bre...


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Mar 20, 2018 10:46PM - edited Mar 20, 2018 10:48PM by marijen

February 13, 2018


https://www.empr.com/clinical-charts/fda-approved-...


FDA-Approved Breast Cancer Treatments Download: FDA-Approved Breast Cancer Treatments FDA-APPROVED BREAST CANCER TREATMENTSGenericBrandStrengthFormUsual DoseALKYLATING AGENTScyclophosphamide25mg, 50mgtabs1−5mg/kg/dayCytoxan injection500mg, 1g, 2gpwd for IV inj after reconstitution40−50mg/kg in divided doses over 2−5 days or 10−15mg/kg every 7−10 days or 3−5mg/kg twice weeklythiotepa15mgpwd for IV, intravesical, or intracavitary admin after reconstitution0.3−0.4mg/kg IV once every 1−4wksANTIBIOTICS (CYTOTOXIC)doxorubicin10mg, 20mg, 50mgpwd for IV inj after reconstitutionMonotherapy: 60−75mg/m² every 21 days
Combination therapy: 40−60mg/m² every 21−28 days2mg/mLsoln for IV injepirubicinEllence2mg/mLsoln for IV infusion100−120mg/m² on Day 1 or divided equally given on Days 1 and 8 of each cycleANTIESTROGENtamoxifen10mg, 20mgtabs20−40mg/daySoltamox Oral Solution10mg/5mLoral solntoremifeneFareston60mgtabs60mg once dailyANTIMETABOLITEScapecitabineXeloda150mg, 500mgtabsMonotherapy: 1250mg/m² twice daily
Combination therapy: Give with docetaxel 75mg/m² IV infused over 1hr every 3wksfluorouracil50mg/mLsoln for IV inj12mg/kg once daily for 4 successive days; max 800mg/daygemcitabineGemzar200mg, 1gpwd for IV infusion after reconstitution1250mg/m² on Days 1 and 8 of each 21‑day cyclemethotrexate25mg/mLsoln for IV, IM, intra-arterial, or intrathecal admin after dilutionSee drug monograph and manufacturer's full labeling1gpwd for IV, IM, intra-arterial, or intrathecal admin after dilutionTrexall5mg, 7.5mg, 10mg, 15mgscored tabsANTIMICROTUBULE AGENTSdocetaxelTaxotere40mg/mLsoln for IV infusion after dilution60−100mg/m² once every 3wkseribulin mesylateHalaven0.5mg/mLsoln for IV inj1.4mg/m² IV inj over 2−5min on Days 1 and 8 of each 21‑day cycleixabepiloneIxempra15mg, 45mgpwd for IV infusion after constitution and dilution40mg/m² once every 3wkspaclitaxelAbraxane100mgIV infusion; inj susp after reconstiution260mg/m² every 3wksTaxol6mg/mLsoln for IV infusion after dilution175mg/m² every 3wksvinblastine10mglyophilized pwd for IV inj or infusion after reconstitution5.5−7.4mg/m² once weekly (see full labeling)1mg/mLsoln for IV inj or infusionAROMATASE INHIBITORanastrozoleArimidex1mgtabs1mg once dailyexemestaneAromasin25mgtabs25mg once dailyletrozoleFemara2.5mgtabs2.5mg once dailyESTROGENconjugated estrogensPremarin0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mgtabs10mg 3 times daily for at least 3mosestradiolEstrace0.5mg, 1mg, 2mgscored tabs10mg 3 times daily for at least 3mosESTROGEN RECEPTOR ANTAGONISTfulvestrantFaslodex50mg/mLsoln for IM injGive by slow IM inj (over 1–2mins). Monotherapy: 500mg on Days 1, 15, 29, then once monthly thereafter.Combination therapy: give with palbociclib 125mg daily with food for 21 days, followed by 7 days off, or with abemaciclib 150mg twice daily; in pre/perimenopausal women: also treat with LHRH agonists.GnRH ANALOGUEgoserelinZoladex3.6mgSC implantOne 3.6mg implant every 28 daysHER2-TARGETED ANTIBODY-DRUG CONJUGATEado-trastuzumab emtansineKadcyla100mg, 160mgpwd for IV infusion after reconstitutionGive by IV infusion only over 90mins. 3.6mg/kg max every 3wks (21‑day cycle) until disease progression or unacceptable toxicity. Subsequent infusions may be given over 30mins if previously tolerated.HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR (HER2) INHIBITORpertuzumabPerjeta420mg/14mL (30mg/mL)soln for IV infusionInitially 840mg IV over 60mins, followed every 3wks thereafter by a dose of 420mg IV over 30–60mins, in combination with trastuzumab. MBC:also give with docetaxel. Neoadjuvant: give every 3wks for 3–6 cycles as part of one of the treatment regimens for EBC (see full labeling). Adjuvant: give every 3wks for 1yr (up to 18 cycles) or until disease recurrence or unacceptable toxicity, whichever occurs first, as part of EBC regimen (see full labeling).trastuzumabHerceptin440mglyophilized pwd for IV infusion after reconstitution and dilutionInitially 4mg/kg over 90mins, followed by 2mg/kg over 30mins weekly; administer until tumor progression. Adjuvant treatment, combination therapy: see full labeling. KINASE INHIBITORabemaciclibVerzenio50mg, 100mg, 150mg, 200mgtabsCombination: 150mg twice daily with fulvestrant (see full labeling); in pre/perimenopausal women: also treat with a gonadotropin-releasing hormone agonist. Monotherapy:200mg twice daily. Both: continue until disease progression or unacceptable toxicity.lapatinibTykerb250mgtabsHER2-positive (metastatic): 1250mg once daily on Days 1–21 continuously in combination with capecitabine 2000mg/m2/day on Days 1–14 in a repeating 21 day cycle; continue until disease progression or unacceptable toxicity. HR-positive, HER2-positive (metastatic): 1500mg once daily continuously in combination with letrozole 2.5mg once daily.palbociclibIbrance75mg, 100mg, 125mgcaps125mg once daily for 21 days followed by 7 days off to complete a 28-day cycle, in combination with an aromatase inhibitor or with fulvestrant 500mg on Days 1, 15, 29, and once monthly thereafter. See full labeling.ribociclibKisqali200mgtabs600mg once daily for 21 days followed by 7 days off to complete 28-day cycle. Take with letrozole 2.5mg once daily, or other aromatase inhibitors, throughout the 28-day cycle. See full labeling.mTOR KINASE INHIBITOReverolimusAfinitor2.5mg, 5mg, 7.5mg, 10mgtabs10mg once dailyPOLY (ADP-RIBOSE) POLYMERASE INHIBITORolaparibLynparza Tablets100mg, 150mgtabs300mg twice daily until disease progression or unacceptable toxicity; max 600mg daily.PROGESTINmegestrol acetate20mg, 40mgscored tabs40mg 4 times dailySELECTIVE ESTROGEN RECEPTOR MODULATOR (SERM)raloxifeneEvista60mgtabs60mg once dailyNOTES

Key: MBC = metastatic breast cancer; EBC = early breast cancer
Not an inclusive list of medications and/or doses. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.

(Rev. 2/2018)

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Mar 21, 2018 12:01AM marijen wrote:

Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo

Laura E. Wright _, Ahmed A. Harhash, Wende M. Kozlow, David L. Waning, Jenna N. Regan, Yun She, Bengt Hallberg, _, Sreemala Murthy, Maryla Niewolna, Andrew R. Marks, Khalid S. Mohammad, Theresa A. Guise

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Oncotarget. 2017; 8:8406-8419. https://doi.org/10.18632/oncotarget.14139

Metrics: PDF 411 views | HTML 311 views | ?


Abstract

Laura E. Wright1, Ahmed A. Harhash1, Wende M. Kozlow2, David L. Waning3, Jenna N. Regan1, Yun She1, Sutha K. John1, Sreemala Murthy1, Maryla Niewolna1, Andrew R. Marks4, Khalid S. Mohammad1, Theresa A. Guise1

1Department of Medicine, Division of Endocrinology, Indiana University, Indianapolis, IN, USA

2Department of Internal Medicine, Division of Endocrinology, University of Virginia, Charlottesville, VA, USA

3Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA

4Department of Physiology, Columbia University, New York, NY, USA

Correspondence to:

Laura E. Wright, email: laewrig@iu.edu

Keywords: breast cancer, bone, metastasis, aromatase inhibitor, skeletal muscle

Received: October 20, 2016 Accepted: November 23, 2016 Published: December 25, 2016

ABSTRACT

Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let). An OVX-Let group was then further treated with bisphosphonate (zoledronic acid; Zol). At week three, trabecular bone volume was measured and mice were inoculated with MDA-MB-231 cells into the cardiac ventricle and followed for progression of bone metastases. Five weeks after tumor cell inoculation, tumor-induced osteolytic lesion area was increased in OVX-Let mice and reduced in OVX-Let-Zol mice compared to sham-vehicle. Tumor burden in bone was increased in OVX-Let mice relative to sham-vehicle and OVX-Let-Zol mice. At the termination of the study, muscle-specific force of the extensor digitorum longus muscle was reduced in OVX-Let mice compared to sham-vehicle mice, however, the addition of Zol improved muscle function. In summary, AI treatment induced bone loss and skeletal muscle weakness, recapitulating effects observed in cancer patients. Prevention of AI-induced osteoclastic bone resorption using a bisphosphonate attenuated the development of breast cancer bone metastases and improved muscle function in mice. These findings highlight the bone microenvironment as a modulator of tumor growth locally and muscle function systemically.

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Mar 21, 2018 12:08AM Lumpie wrote:

Bone metastasis pattern in initial metastatic breast cancer: a population-based study

Conclusion: Our study has reported the epidemiology of patients with bone metastasis in initial MBC based on a general population in the USA. Patients with bone metastasis had a superior prognosis compared to those with visceral/brain metastasis in initial MBC. Incidence and survival differences of initial bone metastasis were well described according to the different molecular subtypes in initial MBC. We also discovered that local surgery could significantly improve cancer survival, suggesting that patients with bone metastasis might consider local surgery in initial MBC.

https://www.dovepress.com/bone-metastasis-pattern-...

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 21, 2018 12:09AM Lumpie wrote:

Hormone receptor status predicts the clinical outcome of human epidermal growth factor 2-positive metastatic breast cancer patients receiving trastuzumab therapy: a multicenter retrospective study

Conclusion: HR status is an independent predictor of overall survival in HER2-positive metastatic breast cancer patients and patients with HER2+/HR- subtype might be associated with more survival benefits when treated with trastuzumab-based regimens.

https://www.dovepress.com/hormone-receptor-status-...

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 21, 2018 12:18AM Lumpie wrote:

Filtration-Based and CellSearch-Based Assessment of CTCs Are Powerful Predictors of Prognosis for MBC Patients

http://www.practiceupdate.com/c/64707/67/13/?elsca...

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 21, 2018 12:25AM Lumpie wrote:

Management of HER2-Positive Breast Cancer With Brain Metastases

http://www.practiceupdate.com/c/65218/67/13/?elsca...

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 21, 2018 05:26PM KPW3 wrote:

This study looks very interesting!

https://medicalxpress.com/news/2018-03-gradual-immunotherapy-site-tumor-surgery.html

Dx 10/2014, IDC, 2cm, Stage IIB, Grade 3, 2/3 nodes, ER+/PR-, HER2- Surgery 1/28/2015 Lumpectomy Chemotherapy 3/2/2015 AC + T (Taxol) Surgery 7/22/2015 Lymph node removal: Underarm/Axillary Radiation Therapy 9/16/2015 Dx 11/29/2017, IDC, Left, Stage IV, metastasized to liver, Grade 3, ER-/PR-, HER2- Chemotherapy 6/13/2018 Halaven (eribulin) Hormonal Therapy Femara (letrozole), Zoladex (goserelin) Chemotherapy Abraxane (albumin-bound or nab-paclitaxel)
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Mar 21, 2018 07:38PM marijen wrote:

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in Nature that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled in Switzerland. Hepatocellular carcinoma is usually diagnosed at a very late stage when the liver is already severely damaged and hence overall prognosis is poor. Detection of the anti-cancer protein LHPP as a biomarker may allow clinicians to provide better treatment options.

New anti-cancer protein LHPP

Liver tumors develop from mutated cells that grow and proliferate uncontrollably. Anti-cancer proteins, so-called tumor suppressors, prevent uncontrolled cell growth. Tumor suppressors are often defective in cancer cells. The researchers led by Prof. Michael N. Hall, Biozentrum of the University of Basel, have now discovered a new, so far unknown tumor suppressor, the protein LHPP. In their study, they show that the loss of LHPP promotes tumor growth and reduces the chance of survival of cancer patients. LHPP could potentially be used as a prognostic biomarker.

The researchers generated a mouse model for hepatocellular carcinoma by activating mTOR signaling specifically in the liver. They analyzed a total of more than 4,000 proteins, comparing them in healthy and tumor tissue. An enzyme emerged as the top favorite: the histidine phosphatase LHPP. "It is striking that LHPP is present in healthy tissue and completely absent in tumor tissue," says first author Sravanth Hindupur. Re-introduction of the genetic information for LHPP by the researchers prevents the formation of tumors and maintains liver function.

Loss of LHPP in cancer patients

"Similar to the mouse model, we also saw a striking decrease in LHPP levels in tumors of patients with liver cancer," says Hindupur. Additionally, both disease severity and life expectancy correlate with LHPP levels. With complete loss of the tumor suppressor, cancer patients die on average two years earlier. LHPP is useful as a biomarker to classify tumors.

Phosphorylation important for tumorigenesis

LHPP is a phosphatase that removes histidine-linked phosphate groups from proteins. Like all amino acids, histidine is a basic component of proteins. Histidine phosphorylation of proteins has been poorly investigated due to the lack of suitable tools. "Tony Hunter, from the Salk Institute in the USA, has provided us with new tools to analyze histidine phosphorylation. We have now been able to visualize a whole new layer of complexity in tumor formation," says Hindupur.

Due to the absence of LHPP, global protein histidine phosphorylation is increased, which can lead to activation of several important functions and uncontrolled cell proliferation. This absence promotes the growth of tumors via increasing histidine-phosphorylated proteins. The tumor suppressor LHPP may also play a role in the development of other cancers.

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Mar 22, 2018 01:07PM Hopeful82014 wrote:

Regarding the article posted by marijen on page 4, re: NCCN recommendations: The following statement comes from an eminent MO and is worth reading to flesh out the situation.

"

Wagner et al have just published a provocative article in BMJ comparing FDA approvals of drugs with recommendations by the NCCN in their guideline panels. (Note: I serve on NCCN guideline panels).

The authors noted that, for new drugs approved between 2011 and 2015, NCCN expert guideline panels recommended additional indications beyond the FDA approved indications 39% of the time. Most of the additional 44 NCCN recommendations for these drugs involved treatment of a different malignancy, removing required prior treatment, or removing trial inclusion criteria. For the different malignancy recommendations, 92% were targeted treatment and 9/12 drugs with additional recommendations were for rare cancers. The authors call into question the quality of the evidence used by the expert panels to make the recommendations and the need to make recommendations beyond the FDA registrations.

I strongly disagree with the aspersion that NCCN panels are making recommendations that they shouldn't. Off-label use of oncology drugs has always been an integral component of cancer care, as manufacturers have not always been inclined to seek regulatory approval for additional indications despite evidence of benefit beyond the registration studies. This is the whole point of compendia, as the treatment of cancer is complex and getting more so given the additional molecular subtypes that respond to targeted therapies. Small populations of patients with a molecular alteration can sometimes show benefit in a different disease state than the cancer for which a drug has been approved. A large phase II or phase III study would be impractical at best when evidence of clinical benefit has been soundly demonstrated, and the NCCN panels are utilizing the available data to expand targeted therapies to other diseases. With regard to recommendations that do not precisely replicate the clinical trial conditions, there is widespread consensus now that clinical trial inclusion and exclusion criteria should be modified to more closely mirror the real-world conditions of patients. The NCCN expert panelists are using these considerations to give access to appropriate therapies to more patients.

The goal of guidelines is to provide the best evidence-based and expert-recommended treatments to patients at given junctions in their disease trajectories. This article's analysis in no way negates the value of NCCN guideline panel recommendations for oncologic therapeutics beyond specific FDA regulatory approval based on careful scrutiny of the available literature, discussion among experts, and consensus of panelists."

Dx IDC
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Mar 22, 2018 01:57PM Hopeful82014 wrote:

Regarding costs of bringing a new drug to market (the figure $11 billion was tossed around above), the Editor in Chief of Kaiser Health News, who is herself a physician, states in a recently published book:

"Pharmaceutical companies like to say it takes well over $1 billion to bring a new drug to market: the costs of the basic science, developing a new compound, figuring out the right dose, and the FDA process of human testing for safety and efficacy. (Many companies also include opportunity costs–the profits that could have been made by investing the money elsewhere–in the estimate.) In some cases, that is likely true. But academic studies have placed the actual average scientific research and development costs for a new drug at between $43.4 million and $125 million. It is unclear how much of PhRMA's typical $1 billion estimate is for testing markets, advertising, and promotion."

Dx IDC
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Mar 22, 2018 03:05PM marijen wrote:

Chemicals in lavender and tea tree oil appear to be hormone disruptors
Date:
March 18, 2018
Source:
The Endocrine Society
Summary:
A new study lends further evidence to a suspected link between abnormal breast growth in young boys -- called prepubertal gynecomastia -- and regular exposure to lavender or tea tree oil, by finding that key chemicals in these common plant-derived oils act as endocrine-disrupting chemicals.
https://www.sciencedaily.com/releases/2018/03/1803...

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Mar 23, 2018 01:24AM marijen wrote:

House Passes Right to Try Bill for Terminally Ill SHARE

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BY: Mary Lou Lang Follow @MaryLouByrd12

March 22, 2018 11:54 am

The U.S. House on Wednesday night passed the Right to Try bill which would give terminally ill patients access to experimental drugs that are in clinical trials but not yet approved by the FDA.

The House passed HR 5257 by a vote of 267-149 and more than 30 Democrats voting with Republicans to pass the bill. It will now go before the Senate which passed a different version of the bill.

President Donald Trump has indicated his support of Right to Try and if it reaches his desk he is expected to sign it into law.

Vice President Mike Pence in a tweet on Thursday morning said, "House & Senate agree: Right-to-Try is a bipartisan PRIORITY. Will continue to work with Congress to get this important bill to @POTUS's desk."

Pence included a photo of Jordan McLinn, an Indiana boy suffering from Duchenne muscular dystrophy, who inspired Pence to sign Right to Try in Indiana when he was governor.

The vote was called a "win for patients" by Goldwater Institute President and CEO Victor Riches, the think-tank which crafted the Right to Try and has pushed for its passage on both the state and federal level.

"Millions of Americans who have been told they are out of options and it's time to get their affairs in order, are closer to having the opportunity for one last treatment, without having to get permission from the federal government first," said Riches in a prepared statement.

"Members of Congress put individual patients ahead of partisan politics and special interests and we're grateful for their support for this bipartisan, grassroots movement powered by real patients in all 50 states," said Riches.

Thirty-eight states since 2014 have enacted Right to Try legislation.

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Mar 23, 2018 11:02AM marijen wrote:

Metastatic lymph nodes can be the source of distant metastases in mouse models of cancer March 22, 2018, Massachusetts General Hospital
https://medicalxpress.com/news/2018-03-metastatic-...

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Mar 23, 2018 09:18PM marijen wrote:

Cancer: How a novel gel could halt its return Published Today

By Honor Whiteman

Fact checked by Jasmin Collier

Groundbreaking research has revealed a promising strategy to stop the recurrence of cancer, and it comes in the form of a biodegradable gel.Destruction of a cancer cellResearchers have developed a gel that could help to stop cancer recurrence and metastasis.

Created by scientists at the Dana-Farber Cancer Institute in Boston, MA, the gel was designed to deliver immunotherapy directly to the area from which a cancerous tumor has been surgically removed.

Upon testing the gel on mice during the surgical removal of breast cancer tumors, the scientists found that it not only helped to prevent tumor recurrence at the primary site, but that it also eliminated secondary tumors in the lungs.

Senior study author Michael Goldberg, Ph.D. — of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute — and colleagues recently reported their results in the journal Science Translational Medicine.

According to the American Cancer Society (ACS), more than 1.7 million new cancer cases will be diagnosed in the United States in 2018, and over 600,000 people will die from the disease.

For cancer that forms as solid tumors — such as breast cancer and lung cancersurgical removal of the tumor is often the primary treatment option.

The problems with immunotherapy

However, as Goldberg explains, even when the tumor is removed, some cancer cells may remain at the site. These can form new tumors, or even spread to other areas of the body. This is a process known as metastasis.

"Indeed, while half of all cancer patients undergo surgery aiming to cure the disease, 40 percent of such patients experience a recurrence of the disease within 5 years," Goldberg notes.

"Furthermore," he adds, "it has been shown that the body's natural process of healing the wound created by surgery can actually spur these residual cancer cells to metastasize to distant parts of the body and form new growths."

Immunotherapy — which involves using drugs to stimulate the immune system and attack cancer cells — can help to prevent cancer recurrence and metastasis. However, the treatment has some serious pitfalls.

A major problem with immunotherapy is that it can attack healthy cells as well as cancerous ones, which can increase a patient's susceptibility to other illnesses.

"In this study," notes Goldberg, "we sought to determine whether administering immune-stimulating drugs at the [right] place and the right time — at the site of tumor removal, before the surgical wound has been closed — could enhance the results of cancer immunotherapy."

'Encouraging' results

For their study, Goldberg and team tested the gel in mice that underwent the surgical removal of breast cancer tumors. The team made the decision to use the gel directly after tumor removal, rather than before.

"We reasoned," Goldberg explains, "that it would be easier to eliminate a small number of residual cancer cells by creating an immunostimulatory environment than it would be to treat an intact primary tumor, which has many means of evading an immune system attack."

Several months after surgery, the mice treated with the gel were much less likely to experience tumor regrowth, compared with rodents that received conventional immunotherapy delivery.

When the researchers injected breast cancer cells into the side opposite to where the original tumor was removed, the gel-treated rodents showed no signs of tumor formation.

Also, the study found that the gel eradicated secondary tumors in the lungs of the mice — that is, it eliminated lung tumors formed from breast cancer cells that had spread from the primary site.

The researchers also replicated their findings in mice with primary lung cancer and melanoma, which is a deadly form of skin cancer.

Based on their results, Goldberg and colleagues believe that their gel-based immunotherapy could be an effective treatment strategy against a number of different cancers.

"This approach has the potential to deliver immunotherapy in a manner that focuses the therapy at the site of interest during a critical time window," he says.

"We are extremely encouraged by the results of this study and hope that this technology will be adapted for patients for testing in clinical trials in the not-too-distant future."
Michael Goldberg, Ph.D.
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Mar 25, 2018 03:12PM marijen wrote:

Trump spending bill

The bill includes increases for every NIH institute and center, and specifically earmarks $1.8 billion for Alzheimer's disease research, a $414 million increase over FY2017; $400 million for the BRAIN Initiative, a $140 million increase over last year; and $290 million for the All of Us precision medicine initiative, a $60 million boost over the previous year. It also provides $5.1 billion to the US Food and Drug Administration — $483 million more than FY2017 — and includes $996 million in 21st Century Cures Act funding.

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Mar 25, 2018 03:25PM marijen wrote:

www.medpage.com

3/24/18 comment on new liquid test PAPSEEK

The U.S. Preventive Services Task Force as well as the ACOG's Choosing Wisely list recommend against screening for ovarian cancer since it is so rare (1.3% lifetime risk). Yet gynecologists remove ovaries (and uteri) at alarming rates. ~300,000 oophorectomies are done at the time of hysterectomy and another ~300,000 separately. The uterus and ovaries have lifelong functions. Numerous studies have shown that removal of any part of the "reproductive" system causes permanent harm.

Currently, GME requires that each resident do at least 70 hysterectomies. Medical education needs to revamp training to emphasize organ-sparing treatments and procedures including myomectomy (fibroid removal) and cystectomy (cyst removal).

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Mar 25, 2018 07:45PM LaurenH wrote:

Focus is on the researcher, herself, but her work is promising

https://www.ozy.com/rising-stars/she-thinks-cancer-drugs-could-use-a-bit-of-protein/83726

Dx 12/2002, IDC, Right, 1cm, Stage IIA, Grade 3, 1/23 nodes, ER+/PR+, HER2+ (FISH) Dx 2/15/2018, IDC, Left, Stage IV, ER+/PR-, HER2+ Targeted Therapy 2/21/2018 Herceptin (trastuzumab) Targeted Therapy 2/23/2018 Ibrance (palbociclib) Radiation Therapy 3/1/2018 External: Bone Hormonal Therapy Arimidex (anastrozole) Targeted Therapy Herceptin (trastuzumab) Chemotherapy AC + T (Taxotere) Surgery Lumpectomy: Right; Lymph node removal: Right, Sentinel, Underarm/Axillary Radiation Therapy Whole-breast: Breast, Lymph nodes Hormonal Therapy Faslodex (fulvestrant)
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Mar 25, 2018 11:58PM Lumpie wrote:

Dr. Sara Hurvitz on Management of HER2-Positive Metastatic Breast Cancer

http://www.practiceupdate.com/c/65219/67/13/?elsca...

{interesting mention of new drugs/drugs in clinical trial.}

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 26, 2018 12:14AM - edited Mar 26, 2018 08:15PM by Lumpie

Metastatic Breast Cancer: HER2 Positive

http://www.practiceupdate.com/c/65641/67/13/?elsca...

If you listen to the very end, Dr. Schwartzberg actually utters prognosis/survival outlook! (Which is helpful for some of us.)

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Mar 26, 2018 03:30PM marijen wrote:

Interesting facts on Brain MRI...

MRI Brain Scan - Detect Brain Tumors and Abnormalities

https://www.scandirectory.com/article/brain-scans/...



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