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Lee21 View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2013 at 12:03pm

Copper depletion therapy keeps high-risk triple-negative breast cancer at bay

New Weill Cornell study shows anti-copper drug might prevent the spread of cancer to organs

NEW YORK (February 13, 2013) -- An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit in one of the most difficult-to-treat forms of cancer -- high-risk triple-negative breast cancer.

The median survival for metastatic triple-negative breast cancer patients is historically nine months. However, results of a new phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows if patients at high-risk of relapse with no current visible breast cancer are copper depleted, it results in a prolonged period of time with no cancer recurrence. In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM).

"These study findings are very promising and potentially a very exciting advance in our efforts to help women who are at the highest risk of recurrence," says the study's senior investigator, Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and professor of medicine at Weill Cornell Medical College.

Dr. Vahdat says four of the study participants with a history of metastatic triple-negative breast cancer have had long-term benefit remaining disease free for between three and five and a half years.

"The anti-copper compound appears to be keeping tumors that want to spread in a dormant state," reports Dr. Vahdat, who is also medical oncologist at the Iris Cantor Women's Health Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "We believe one of the important ways it works is by affecting the tumor microenvironment, specifically the bone marrow-derived cells that are critical for metastasis progression."

In addition, study participants with other forms of high-risk for relapse breast cancers -- either stage 3 or stage 4 -- without evidence of disease after treatment have also fared well. The progression-free survival rate among these 29 patients in the study has been 85 percent, to date.

"As good as these interim findings look to us, we cannot talk about significant benefit until we compare TM treatment to other therapies," she says. Dr. Vahdat expects to launch a phase III randomized clinical trial in the near future.

This research is a report of the first 40 patients. The clinical trial, which began in 2007, has been expanded many times and now includes 60 patients, more than half of who have triple-negative breast cancer.

Deplete Copper to Prevent Cancer Spread

New discoveries in the science of metastasis and examination of the body's utilization of copper to promote cancer spread led to this clinical trial.

Investigators at Weill Cornell, including some of this study's co-authors, have contributed to the recent understanding of the role bone marrow cells play in promoting metastasis. They previously found that a collection of bone marrow-derived cells, which include VEGFR1+ hematopoietic progenitor cells (HPCs), prepare a site in distant organs to accept cancer cells. HPCs also recruit endothelial progenitor cells (EPCs), among others, to activate an "angiogenic switch" that establish blood vessels at the site to feed newly migrated cancer cells.

Breast cancer research studies conducted at Weill Cornell have also found that immediately prior to cancer relapse, levels of EPCs and HPCs rise significantly further, suggesting that the EPC target of the copper depletion approach is one that makes sense.

"Breast tumors want to move to specific organs, and these EPCs and HPCs cells leave a 'popcorn trail' for cancer cells to follow, as well as provide the building blocks for blood vessels to greet them as they arrive," Dr. Vahdat says.

Copper is critical to mobilizing these cells. Copper is essential to the metastatic process. It is a key component of enzymes that help turn on angiogenesis in the tumor microenvironment, and it also appears to play a role in directing cancer cell migration and invasion, according to researchers.

TM is a copper chelation compound used to treat Wilson's disease, a hereditary copper metabolism disorder, and has been studied in phase I and phase II clinical trials for a number of disorders. Animal studies have demonstrated that depleting copper decreases proliferation of EPCs, as well as blood vessel formation and tumor growth.

Dr. Vahdat's study is the first human clinical trial to utilize a copper depletion strategy to modulate EPCs in breast cancer patients with an extraordinarily high risk of relapse from hidden residual disease. Most of the studies in other solid tumors with visible advanced disease have been disappointing, say researchers.

Despite improvements in breast cancer therapy, there is significant risk of relapse in a high-risk subset of patients. The risk of relapse in stage 3 patients is 50-75 percent over five years, and patients with stage 4 breast cancer always recur. Triple-negative breast cancer patients have a poorer prognosis even when diagnosed in early disease stages.

"These triple-negative patients represent a substantial proportion of metastatic breast cancer patients," says Dr. Vahdat. "These are the patients that need the most attention, which is why we have focused most of the resources of our Metastases Research Program on this problem."

In the study, researchers found that 75 percent of patients achieved the copper depletion target using TM after one month of therapy, and that copper depletion was most efficient (91 percent) in patients with triple-negative tumors, compared to other tumor types (41 percent). In copper-depleted patients only, there was a significant reduction in EPCs, and the 10-month relapse-free survival was 85 percent. In addition, TM was found to be safe and well-tolerated in patients.

The study shows copper depletion appears to inhibit the production, release, and mobilization of EPCs from the bone marrow, leading to a suppressed angiogenic switch and tumor dormancy.

"There are a lot of cancer experts at Weill Cornell working very hard to understand this precise mechanism, define the clinical benefit in this ongoing copper depletion drug clinical trial, and determine its future study," says Dr. Vahdat. "Keeping cancer dormant is what we all want for our patients -- especially triple-negative breast cancer patients at highest risk of recurrence."

###

Study co-authors include Dr. Sarika Jain, Maureen M. Ward, Naomi Kornhauser, Dr. Ellen Chuang, Dr. Tessa Cigler, Dr. Anne Moore, Diana Donovan, Christina Lam, Marta V. Cobham, Sarah Schneider, Sandra M. Dr. Hurtado Rúa, Celine Mathijsen Greenwood, Dr. Richard Zelkowitz, Dr. J. David Warren, Dr. Maureen E. Lane, Dr. Vivek Mittal and Dr. Shahin Rafii from Weill Cornell; Dr. Jules Cohen from Stony Brook University Cancer Center, Stony Brook, N.Y.; and Steven Benkert from NewYork-Presbyterian Hospital.

The study was funded by the grants from the Anne Moore Breast Cancer Research Fund, Stephen and Madeline Anbinder Foundation, Rozaliya Kosmandel Research Fund, Susan G Komen for the Cure, New York Community Trust, Cancer Research and Treatment Fund, Manhasset Women's Coalition Against Breast Cancer and Berman Fund.

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Charlene View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Charlene Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2013 at 12:45pm
Question:  I take a multivitamin that contains copper.  I had heard before that copper wasn't really so advisable.  Do you think I should stop?  Hmmm...definitely something to thing about.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2013 at 1:34pm
Copper is an essential trace element for us vertebrates and is required for the function of a number of enzymes. Copper deficiency leads to a number of disorders. Like everything else, I think is a balance. The study cited above is just a phase 2 with a small # of patients and adverse reactions were encountered including hematological, GI and neurological. 
In answer to your question, personally I don't think is an issue but you might want to check w/ your doc. According to WebMD, people eating a normal diet doesn't require copper supplementation. It might be hard to find a multivitamin w/o copper.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Charlene Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2013 at 2:00pm
Lee,
Thank you for being such a great resource on this forum!!
Charlene
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 02 2013 at 11:45am
Web address:
     http://www.sciencedaily.com/releases/2013/04/
     130401074911.htm

Surgical Removal of Lung Metastases in Breast Cancer Patients May Improve Overall Survival

Apr. 1, 2013 — Patients with primary breast cancer that has spread to the lungs may live longer if the lung metastases are surgically removed, according to a study published in the April 2013 issue of The Annals of Thoracic Surgery.

Georgios Meimarakis, MD, Hauke Winter, MD, PhD, and colleagues from Ludwig-Maximilians-University in Munich, Germany, examined factors that influenced the long-term survival of patients with isolated pulmonary metastases of primary breast cancer following surgical removal of the metastases (pulmonary metastasectomy).

Metastatic breast cancer (mBC) is a stage identified when the disease has spread to distant, non-adjacent organs or areas. The median survival of patients with mBC treated with conventional chemotherapeutic regimens ranges from 12 months to 24 months, and it previously had been assumed that these patients would not benefit from surgical intervention.

The researchers found that, with metastasectomy, the median overall survival increased to as much as 103.4 months.

"Before this study, no randomized trial had examined prospectively the impact of metastasectomy on survival compared to conservative therapeutic strategies," said Dr. Meimarakis.

Between 1982 and 2007, 81 patients with a median age of 58.2 years (range 28.3 to 76.3 years) were recruited for the study.

In 81.5% of patients (66), complete removal of all tumors was observed, with microscopic examinations showing no remaining tumor cells (R0 resection). In 7.4% of patients (6), some tumors cells were still visible microscopically (R1 resection) and 11.1% of patients (9) showed portions of remaining tumors visible to the naked eye (R2 resection).

R0 resection was associated with significantly longer median overall survival than R1 or R2 resection (103.4 months, 23.6 months, and 20.2 months, respectively). Additional analysis revealed that R0 resection, and number and size of metastases were factors that affected long-term survival.

Dr. Meimarakis noted: "Too often patients with mBC are not considered for surgical treatment, as it is assumed that these patients would not benefit from surgical interventions for various reasons. Based on our findings we highly recommend surgeons consider patients with isolated pulmonary metastases for surgical resection."

Cancer treatment teams need to consider metastasectomy

In an invited commentary appearing in the same issue, Hans Hoffmann, MD, from The University of Heidelberg in Germany, noted that this study adds meaningful data to the available body of evidence that breast cancer patients with a suspected first recurrence are most likely to gain substantial benefit from an intensified multidisciplinary therapeutic approach.

"As the morbidity and mortality of pulmonary resection has decreased substantially over the last decades, this potentially beneficial procedure should be discussed and considered more often than not in an intensified multidisciplinary therapeutic approach," said Dr. Hoffmann.

Link to journal article:

http://ats.ctsnetjournals.org/cgi/content/abstract/95/4/1170

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Wade Quote  Post ReplyReply Direct Link To This Post Posted: Apr 02 2013 at 11:54am
Thanks for this article, Lee. 

It's great to see such a big improvement. I hope you are well!

Best regards,
Wade
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Apr 02 2013 at 2:03pm
Lee,

Your article brings up a good topic about treating mets.  My friend was diagnosed almost 3 years ago with Stage 4 Peritonneal Cancer (similar to Ovarian).  Besides chemo, she's had 3 de-bulking surgeries (one that resected part of the liver) that I believe have helped her have a good quality of life and live longer than the original prognosis.  Her oncologist didn't want her to have the last surgery and just wanted to do more chemo.  She consulted with a top liver surgeon who agreed to perform the surgery.  I think it's something patients should investigate further with a good, qualified surgeon.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 03 2013 at 2:03pm
I thought the article was interesting and therefore posted it.  The study cohort is highly selected though, patients with only lung mets -- how common is that? Also the patients who do best are the ones with solitary lung mets < 3 cm.  It is something to keep in mind.  With TN, it seems like when metastasis is detected, there are mets in multiple organs.
Maybe it argues for closer surveillance.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 05 2013 at 1:20pm

Don't take cancer sitting down

A new survivorship research agenda

Abstract

Cancer survival is associated with considerable physical and psychosocial burden. Broadly accessible, nonpharmacologic measures that may extend disease-free survival, limit comorbid disease, and enhance quality of life are required. Sedentary behavior (too much sitting) is now understood to be a health risk that is additional to, and distinct from, the hazards of too little exercise. Of particular note, it is associated with adiposity, insulin resistance, and markers of inflammation. Therefore, it is plausible that sedentary behavior may contribute to adverse cancer outcomes (disease progression, recurrence, or death) and to the development of comorbid chronic disease. Initial studies indicate that cancer survivors spend two-thirds of their waking hours sitting. Among colorectal cancer survivors, sedentary behavior may contribute to all-cause and disease-specific mortality, weight gain, comorbid cardiovascular disease, and diminished quality of life. There is a need for dose-response evidence, and for a broader understanding of the underlying mechanisms by which prolonged sitting time may affect cancer survivors' health. Cancer 2013. © 2013 American Cancer Society.

http://onlinelibrary.wiley.com/doi/10.1002/cncr.28028/abstract


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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 11 2013 at 2:03pm


A Dickens Tale of the Treatment of Advanced Breast Cancer: The Past, the Present, and the Future



Category:
Breast Cancer

Meeting:
2012 Educational Book

Author(s):
By George W. Sledge Jr., MD, Fatima Cardoso, MD, Eric P. Winer, MD, and Martine J. Piccart, MD

Article Summary:

Overview: Metastatic breast cancer (MBC), a usually incurable disease, continues to vex physicians and patients. Recent decades have seen great improvements in the treatment of MBC, based on the availability of novel targeted therapeutics and more standard chemotherapeutic agents. This article describes the goals of therapy for MBC, the progress made against MBC in recent decades, the current standard of care, and the ongoing efforts of basic and translational researchers to transfer the fruits of modern scientific discovery to patients in the clinic.

Full Article - go to this link, then click on the "View Full Educational Article" to download pdf.

http://origin.asco.org/ASCOv2/Education+%26+Training/Educational+Book?&vmview=edbk_detail_view&confID=114&abstractID=306




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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 13 2013 at 6:11pm
Breast Cancer Res Treat. 2013 Mar 31. [Epub ahead of print]

The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients.

Source

Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, 1475 NW 12th Avenue, D8-4, Miami, FL, 33136, USA, jhurley@miami.edu.

Abstract

Triple-negative breast cancers comprise about 20 % of breast cancers. They have poor prognosis and have no standard therapy. The aim of this study was to evaluate pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based chemotherapy. This is a retrospective study of one hundred and forty-four women with TNBC treated with neoadjuvant platinum-containing chemotherapy for locally advanced breast cancer at the University of Miami between January 1, 1999, and January 1, 2011. The medical record was reviewed to obtain data on clinical characteristics, including ethnicity, race, age, clinical stage, treatment regimen, and vital status. This study was approved by the University of Miami IRB. All patients had locally advanced breast cancer with at least one of the following features at presentation: T3, T4, N2, and N3. The mean tumor size by palpation was 9.4 cm. The clinical T-stage at presentation was 1.4 % T1, 8.3 % T2, 52.8 % T3, and 37.5 % T4 (19.4 % T4d). The nodal status by physical exam at presentation was 23 % N0, 37.5 % N1, 34 % N2, and 5.5 % N3. pCR in breast and axilla was seen in 31 %. PFS and OS were 55 and 59 %, respectively, at 7 years. Cisplatin offered a survival advantage over carboplatin in both PFS (P = 0.007) and OS (P = 0.018). Node positivity was the most important predictor of survival. Cisplatin/docetaxel neoadjuvant therapy was well tolerated and an effective therapy in locally advanced TNB.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 15 2013 at 11:19am
Catheters and Ports in Cancer Treatment

From time to time, questions have come up related to ports, placed for venous access to IV drugs.  I came across this link (cancer.net) that offers authoritative information:
http://www.cancer.net/all-about-cancer/cancernet-feature-articles/cancer-basics/catheters-and-ports-cancer-treatment

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: May 30 2013 at 2:56pm

Breast-Conserving Therapy Achieves Locoregional Outcomes Comparable to Mastectomy in Women with T1-2N0 Triple-Negative Breast Cancer.

Ann Surg Oncol Epub May 19, 2013

Abstract

BACKGROUND:

Conflicting data exist regarding optimum local therapy for early-stage triple-negative breast cancer (TNBC). We examined outcomes according to local treatment type in a large cohort of node-negative TNBC patients.

METHODS:

A total of 1,242 consecutive patients with TNBC treated at a single institution from 1999 to 2008 were identified. Of these, 646 with pathologic stage T1-2N0 TNBC underwent breast-conserving therapy (BCT) (N = 448) or total mastectomy (TM) without postmastectomy radiation (N = 198) and comprised the study population. Locoregional recurrence (LRR), distant metastasis (DM), and overall recurrence were investigated with a competing risk analysis using Gray's test and multivariable Fine and Gray competing risk regression. Overall survival was assessed using standard Kaplan-Meier methods and a Cox proportional hazards analysis.

RESULTS:

Median follow-up was 78.3 months (range 1-156). Eight-one percent of patients received adjuvant chemotherapy. TM patients were younger, were more likely to have lymphovascular invasion, and had larger tumors than patients undergoing BCT (all P ≤ 0.05). The 5-year cumulative incidence of LRR was 4.2 and 5.4 % for patients undergoing BCT and TM, respectively. There was no significant difference in LRR, DM, overall recurrence, disease free survival, or overall survival between groups on univariate analysis, or after adjusting for other variables in multivariate models. Lack of chemotherapy and high tumor stage independently predicted for decreased overall survival (both P < 0.001).

CONCLUSIONS:

A low, 5-year risk of LRR (4.7 %) was achieved in a large group of women with T1-2N0 TNBC treated with multimodality therapy. BCT was as equally effective as TM for local and distant control.

http://www.ncbi.nlm.nih.gov/pubmed/23686101


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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jun 05 2013 at 11:07pm
ASCO 20132:  Dose dense Taxol vs. weekly Taxol, no difference in survival.

http://www.medpagetoday.com/HematologyOncology/BreastCancer/39636
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jun 06 2013 at 10:26am

Here's the actual abstract.

S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.

Subcategory: 
Cytotoxic Chemotherapy
Session Type and Session Title: 

Oral Abstract Session, Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy

Abstract Number: 

CRA1008

Citation: 

J Clin Oncol 31, 2013 (suppl; abstr CRA1008)

Author(s): 

G. Thomas Budd, William E. Barlow, Halle C. F. Moore, Timothy J. Hobday, James A. Stewart, Claudine Isaacs, Muhammad Salim, Jonathan K. Cho, Kristine Rinn, Kathy S. Albain, Helen K. Chew, Gary Von Burton, Timothy David Moore, Gordan Srkalovic, Bradley Alexander McGregor, Lawrence E. Flaherty, Robert B. Livingston, Danika Lew, Julie Gralow, Gabriel N. Hortobagyi; Cleveland Clinic, Cleveland, OH; Cancer Research and Biostatistics, Seattle, WA; Mayo Clinic, Rochester, MN; Baystate Medical Center, Springfield, MA; Lombardi Comprehensive Cancer Center, Washington, DC; Allan Blair Cancer Center, Saskatoon, SK, Canada; Oncare Hawaii, Honolulu, HI; Swedish Cancer Institute, Seattle, WA; Loyola University Medical Center, Maywood, IL; University of California, Davis Cancer Center, Sacramento, CA; LSU Health Sciences Center, Shreveport, LA; Mid Ohio Oncology Hematology, Inc., Columbus, OH; Sparrow Regional Cancer Center, Lansing, MI; Willford Hall Medical Center, Lackland, TX; Wayne State University School of Medicine, Detroit, MI; Arizona Cancer Center, Tucson, AZ; Southwest Oncology Group Statistical Center, Seattle, WA; Seattle Cancer Care Alliance, Seattle, WA; The University of Texas MD Anderson Cancer Center, Houston, TX

Background: S0221 is a SWOG-coordinated phase III adjuvant chemotherapy intergroup trial in node-positive and high-risk node-negative operable breast cancer which hypothesized that 1) the weekly AC+G regimen is superior to ddAC x 6 and 2) 12 weeks of weekly paclitaxel (wP) is superior to q 2 week paclitaxel x 6 (ddP). Methods: Between December 2003 and November 2010, 2,716 patients were randomized in a 2 x 2 factorial design to 1) AC+G vs ddAC and 2) P 80 mg/m2/week x 12 vs P 175 mg/m2 q 2 weeks x 6. If there was no significant interaction between the factors, the trial was powered to find a disease-free survival hazard ratio (HR) ≤ 0.82 for weekly vs q 2 week for each factor. At the first interim analysis, the AC randomization was halted for futility, and S0221 was closed to accrual 10 November 2010. S0221 reopened 15 December 2010, after which time all patients received 4 cycles of ddAC and randomization to P weekly x 12 and ddP x 6 continued. Accrual halted at a total of 3,294 in January 2012. Results: By September 7, 2012, 487 events and 340 deaths had occurred, prompting the third planned interim analysis. The Data Safety and Monitoring Committee recommended reporting the results since the futility boundary was crossed. A Cox model adjusting for the AC arms had a HR = 1.08 (95% CI 0.90-1.28; p=0.42), with the 99.5% CI excluding the original alternative hypothesis that the HR=0.82. There was no significant interaction of the two factors. Estimated 5-year progression-free survivals were 82% for weekly P and 81% for ddP. Toxicity data were available for 1,385 patients treated with ddP and 1,367 treated with weekly P. Grade 5 toxicity occurred in 4 patients on ddP and 2 on weekly P. Percent grade 3-4 toxicity per arm are shown in the Table. Conclusions: Either ddPx6 or weekly P x 12 are acceptable schedules of P administration. The differences in leukopenia likely reflect ascertainment bias against weekly P. If this is accepted, weekly P x 12 produces less overall toxicity than 6 cycles of ddP. Support: NCI grants CA32102, CA38926, CA21115, CA21076, CA77597, CA25224, CA77202, CCSRI15469, and Amgen, Inc. Clinical trial information: NCT00070564.

Grade 3-4 toxicity ddP Weekly P
Any 36% 35%
Allergy 14% 6%
Leukopenia 1% 6%
Neutropenic fever <1% <1%
Dermatologic 3% 0.1%
Musculoskeletal pain 11% 3%
Neurologic 17% 10%

12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jun 14 2013 at 4:05pm

Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE

  1. on behalf of EMBRACE

+ Author Affiliations

  1. Affiliations of authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care (NM, SP, DF, SE, RP, EF, ACA, DFE); Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK (DGE); South East Thames Regional Genetics Service, Guy’s Hospital, London, UK (LI); Oncogenetics Team, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK (RAE); Yorkshire Regional Genetics Service, Leeds, UK (JA); Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK (RD); Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK (DE); West Midlands Regional Genetics Service, Birmingham Women’s Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK (TC); Sheffield Clinical Genetics Service, Sheffield Children’s Hospital, Sheffield, UK (JC); Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK (CB); Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK (MT); Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK (FD); Clinical Genetics Department, St.Georges University of London, Tooting, London, UK (SH); Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK (LW); South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK (MEP); Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK (PJM); North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, UK (LES); Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St James’s Hospital, Dublin, Ireland (MJK); Cheshire & Merseyside Clinical Genetics Service, Liverpool Women’s NHS Foundation Trust, Liverpool, UK (CH); South West Regional Genetics Service, Bristol, UK (AD); All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK (MTR); North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK (HD); North of Scotland Regional Genetics Service, NHS Grampian & University of Aberdeen, Foresterhill, Aberdeen, UK (ZM, HG); Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, UK (JE); Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK (JB); All Wales Medical Genetics Service, Glan Clwyd Hospital, Rhyl, UK (EM, AM).
  1. Correspondence to: Nasim Mavaddat, MBBS, PhD, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK (e-mail: nasim@srl.cam.ac.uk).
  • Received July 24, 2012.
  • Revision received March 20, 2013.
  • Accepted March 22, 2013.

Abstract

Background Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers. The aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles.

Methods Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks were obtained using Kaplan–Meier estimates. Associations between cancer risk and covariables of interest were evaluated using Cox regression. All statistical tests were two-sided.

Results The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2 carriers in the highest tertile of risk, defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk, were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile (hazard ratio = 4.1, 95% CI = 1.2 to 14.5; P = .02).

Conclusions Prospective risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast, ovarian, and contralateral breast cancer. Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.

  1. JNCI J Natl Cancer Inst 105 (11): 812-822. doi: 10.1093/jnci/djt095 First published online: April 29, 2013



Edited by Lee21 - Jun 14 2013 at 4:20pm
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jun 14 2013 at 4:11pm

Relating Neuropsychological Test Performance To Cognitive Complaints After Breast Cancer

Approximately one out of five breast cancer patients treated for breast cancer had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific neuropsychological (NP) test performances and depressive symptoms. Combined chemotherapy and radiation treatment in these patients was also associated with memory complaints according to a study published April 18 in the Journal of the National Cancer Institute.

Cognitive complaints have been frequently reported following breast cancer treatments, however, their connection with neuropsychological (NP) test performance has not been well established.

In order to determine the relationship between cognitive complaints and neurocognitive testing, Patricia A. Ganz, M.D., at the Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center and colleagues, looked at early-stage post treatment breast cancer patients who were enrolled in a prospective, longitudinal, cohort study before they started receiving endocrine therapy and evaluated them using an NP test battery and questionnaires that were self-reported, which gauged their symptoms, including cognitive complaints.

The researchers found that of the 189-breast cancer patients evaluated, 23.3% had higher memory complaints and 19% reported higher executive function complaints than found in age-matched healthy women without breast cancer. They also found that higher memory complaints were statistically significantly associated with combined chemotherapy and radiation treatments, and not chemotherapy alone. “Our findings add further support for the value of patient-reported outcomes as a central measurement in evaluation of cancer treatment-related morbidities,” the authors write.

In an accompanying editorial, Christina A. Meyers, Ph.D., M.D. Anderson Cancer Center, writes that the studies that use subject data can obscure individual differences and may underestimate the true incidences of cognitive symptoms in breast cancer patients and feels that, “many cancer survivors can enjoy improved levels of functioning if properly diagnosed and provided with the right support.”

  1. JNCI J Natl Cancer Inst 105 (11): 1. doi: 10.1093/jnci/djt112 First published online: April 18, 2013
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Jul 29 2013 at 12:50pm
TNBC Foundation just posted on their Facebook page:

"Aggressive breast cancer genes found.
Scientists at A*STAR’s Genome Institute of Singapore (GIS) led a study that has identified genes that are potential targets for therapeutic drugs against aggressive breast cancer. These findings were reported in the July 2013 issue of PNAS........They also showed that patients with TNBC tumours that have high levels of UBASH3B tend to be more likely to have early recurrence and metastasis......The scientists discovered that a protein tyrosine phosphatase, called UBASH3B, is overexpressed in one third of TNBC patients. UBASH3B controls the activity of an important breast cancer gene."
Article at:
http://www.sciencealert.com.au/news/20132807-24630.html
with source of http://www.a-star.edu.sg/Media/News/PressReleases/tabid/828/articleType/ArticleView/articleId/1855/Default.aspx


Grateful for today.............Judy

Edited by Grateful for today - Jul 29 2013 at 12:51pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 04 2013 at 9:22pm
Added on page 4 of this thread:

RADIOLOGY
Patient Safety: Radiation Dose in X-Ray and CT Exams                                
http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray
My Medical Imaging History
http://www.radiologyinfo.org/en/safety/ImageWisely/7678_Medical%20Imaging%20History.pdf

In addition to getting copies of the imaging tests one has, one can consider keeping a self made history
list with the date, name of test, (amount of radiation if known).


Grateful for today...........Judy

-------------------------------

Added to page 4:

GENES

Gene Reviews.
Expert-authored summaries about diagnosis, management and genetic counseling for specific inherited conditions, University of Washington.
http://www.ncbi.nlm.nih.gov/books/NBK1116/

Among some of the topics covered:
BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer
http://www.ncbi.nlm.nih.gov/books/NBK1247/
Li-Fraumeni Syndrome
http://www.ncbi.nlm.nih.gov/books/NBK1311/

Edited by Grateful for today - Aug 10 2013 at 7:02pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Aug 22 2013 at 9:21pm
Progress in the Biological Understanding and Management of Breast Cancer-Associated Central Nervous System Metastases
  1. Ana M. Gonzalez-Angulo
First published online in THE ONCOLOGIST Express on June 5, 2013.

Abstract

Metastasis to the central nervous system (CNS) is a devastating neurological complication of systemic cancer. Brain metastases from breast cancer have been documented to occur in approximately 10%–16% of cases over the natural course of the disease with leptomeningeal metastases occurring in approximately 2%–5% of cases of breast cancer. CNS metastases among women with breast cancer tend to occur among those who are younger, have larger tumors, and have a more aggressive histological subtype such as the triple negative and HER2-positive subtypes. Treatment of CNS metastases involves various combinations of whole brain radiation therapy, surgery, stereotactic radiosurgery, and chemotherapy. We will discuss the progress made in the treatment and prevention of breast cancer-associated CNS metastases and will delve into the biological underpinnings of CNS metastases including evaluating the role of breast tumor subtype on the incidence, natural history, prognostic outcome, and impact of therapeutic efficacy.

http://theoncologist.alphamedpress.org/content/18/6/675.long
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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