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Old 11-13-2006, 11:52 AM   #1
Lani
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"WE are confident vaccine prevents bc by preventing her2+ DCIS shows efficacy

Novel vaccine shows promise against early-stage breast cancer [American Association for Cancer Research]
BOSTON - A diagnosis of breast cancer has taken on a new meaning in the past 10 years, as research has produced a host of new therapies and detection techniques, significantly improving long-term survival for women who have been fighting the disease. To build on these successes, researchers are now harnessing what they have learned about treating breast cancer and applying it to possible methods of prevention to reduce the total incidence of the disease. One study presented today at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting in Boston looks at a specific target in the fight against breast cancer and evaluates a potential vaccine that is yielding promising results for women who are at high-risk for the disease.

Targeted immunoediting of critical pathways responsible for breast cancer development: treatment of early breast cancer using HER-2/neu pulsed dendritic cells

Multiple genetic targets have been discovered that may help fight breast cancer, including BRCA, estrogen receptors, and HER-2/neu, all of which have been known to predict the severity of disease, recurrence and overall survival. Developing novel therapies that target these specific genetic variances may be extremely beneficial in preventing breast cancer for many women.

In this study, researchers investigated a potential vaccine that targets HER-2/neu over-expression in early stage breast cancer, known as DCIS (ductal carcinomas in situ, or early stage cancer formation in the breast's milk ducts). It is estimated at 50-60 percent of DCIS is directly related to HER-2/neu over-expression.

Patients with HER-2/neu overexpression were given a therapy of dendritic cells (DC, which work with the B- and T-cells to trigger immune responses) that were treated with HER-2/neu to evoke an immune response. The participants received four weekly vaccinations into normal lymph nodes in their groins and were evaluated both pre- and post-vaccination for immune response, level of HER-2/neu expression, and cell infiltrates.

The researchers found that most patients responded well to the vaccination. Nearly all patients (11 of 12) exhibited an initial immune response (shown by the presence of anti-HER-2/neu specific CD4+ T cells), and many of the patients developed protein antibodies to fight the HER-2/neu cells
CONTINUED...
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Old 11-13-2006, 12:01 PM   #2
Lani
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the long awaited "kicker"

2500 character restriction and difficulty accessing website caused the delay:
Patients began to build up reserves of white blood cells following treatment and seemed to show long-term immune responses to HER-2/neu as a result of the therapy. Of the 12 study participants, six showed markedly reduced levels of HER-2/neu expression after the vaccination, and as a result, the investigators also noted an improvement in their severity of their disease.

"The results demonstrate for the first time that this DC vaccination may have significant clinical activity against certain types of breast cancer," said Brian J. Czerniecki, M.D., of the University of Pennsylvania, and lead author of the study. "We are confident that targeted treatment with this vaccine may effectively fight not only DCIS, but may extend to prevention of breast cancer entirely."
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Old 11-14-2006, 10:13 PM   #3
skibunny
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Smile

Dear Lani,

This is the clinical trial I was a part of at HUP. If you would like more Information I would be glad to share it. Where did you read about this. Dr.Czerniecki told me he was going to this conference and that there would be a release to the media about the study.

Also. I have to tell you how impressed I am with your knowledge. How do you find out about the latest information on HER2 and where do you find the information to answer everyone's questions?

You have been so helpful in keeping me informed and educated about breast cancer.

Thank you,

Ski bunny
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Old 11-15-2006, 12:37 AM   #4
Lani
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Ski Bunny

I review Pub Med five days a week (they don't add anything Sunday or Monday) on breast cancer, as well as Breast cancer research and periodically Artemis (from Johns Hopkins), aacr publications, nci publications, and get on the list for various newsletters.

I look when conferences are being held and try to look up abstracts, news releases resulting from the conferences.

I read the BBC site daily and health information in the Wall St. Journal (lets me know when applications are made for fast-track approval, when FDA approvals occur) as well as Medscape News.

And that is just for breast cancer. I am helping several people with other problems research treatment possibilities including prostate cancer, esophageal cancer and avascular necrosis of the hip at the moment (it changes as different people ask me to research different things for them)

Tonight I just returned from a webcast simulcast of Dr. Mark Pegram and Dr. Cliff Hudis on her2 breast cancer--including the discussion of a lot of planned clinical trials of lapatinib with and without herceptin, Lapatinib and an AI, avastin and a taxane etc for early breast cancer.

They also discussed how they might treat the very elderly with herceptin and antihormonal therapy without chemo (I am trying to inform an 84 year old with her2+ breast cancer of her options).

They made it sound like there are going to be lots of important new revelations in San Antonio.

Let's hope so!
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Old 11-15-2006, 10:40 AM   #5
skibunny
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Question Perhaps you can guide me

Dear Lani,

Thank you for your information. Perhaps you can guide me on how to relieve back pain for my 87 year old mom who has breast cancer that has metastized to her back. My sister is with her in Florida and told me the x-rays show black dots along her spine which are tumors pressing on her bones which have caused them to crack. She just finished 16 days of radiation which was supposed to relieve pain and shrink the tumors. It has not done so. She was on Arimidex for 1/12 years after her bilateral mastectomy and the Dr. has switched her to Tamoxifin saying the Arimidex didn't work. She had a CAT scan of her body and the cancer has not spread anywhere else. She is taking oxycontin which is not helping. She was like the energizer bunny taking care of my 87 year old dad before this back pain started 2 months ago. Do you know of any treatments, medication, Dr. specialists, etc. for this? She lives in south Florida near Hollywood and Fort Lauderdale.

Thank you ,

Skibunny
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Old 11-15-2006, 06:04 PM   #6
Lani
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Ski bunny

I am not an oncologist, radiation therapist, oncology nurse, pharmacist or other with personal treatment experience but I can tell you from my reading:

1) when there are but a few of these there is a procedure by which orthopaedic surgeons inject bone cement into the vertebral body (the shape of a marshmallow normally) after an instrument has "jacked" up the height of the vertebra prior to injecting the cement. I suppose sometimes they don't jack it up much and just inject the cement in. It is called a vertebroplasty and keeps the bone from collapsing further IF this is the source of the pain rather than the nerves or spinal cord being impinged upon. Jacking up the vertebral body to its old height can relieve some symptoms of of impingement, but I don't know how many vertebral bodies can be involved before they decide it is too many to try to treat them all. It is a minimally invasive surgery, but a surgery and if you mom's condition is not that great that might influence whether they would consider it.
I will see if I can find any articles discussing how many might be too many

2) I am not a pharmacist but there are several papers on intravenous bisphosphonates for hypercalcemia from bone mets and that they seem to relieve bony pain from the mets as well sometimes.

I was trying to post some but this 2500 character rule botched it up.

Will have to return to do this later....
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Old 11-15-2006, 07:27 PM   #7
Lani
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am having trouble accessing this article hot off the press but will keep trying

Lancet Oncol. 2006 Nov;7(11):894. Links
Zoledronic acid palliation in bone-metastatic breast cancer.

Furlow B.
PMID: 17099983 [PubMed - in process]
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Old 11-15-2006, 07:30 PM   #8
Lani
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here is an earlier article...in segments due to 2500 character restriction

Drugs. 2004;64(11):1197-211. Links
Zoledronic acid: a review of its use in patients with advanced cancer.

Perry CM,
Figgitt DP.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose of zoledronic acid showed good efficacy in the treatment of patients with hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum calcium concentrations 10 days after administration. In conjunction with antineoplastic therapy, zoledronic acid was an effective long-term (up to 25 months) treatment for skeletal-related events in patients with bone metastases associated with multiple myeloma or solid tumours. In patients with bone metastases secondary to breast cancer or bone lesions from myeloma, zoledronic acid was at least as effective as pamidronic acid, based on assessments of skeletal-related events 25 months after the start of treatment. In addition, compared with pamidronic acid, the overall risk of developing skeletal complications, including hypercalcaemia of malignancy, was significantly reduced in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid reduced the risk of patients with breast cancer developing a skeletal-related event by an additional 20%.
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Old 11-15-2006, 07:30 PM   #9
Lani
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continued...

Zoledronic acid was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to 15 months. Preliminary data indicate that its efficacy in these patients is sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic acid in the treatment of prostate cancer were consistent with those of other bisphosphonates, and cost-effectiveness ratios were within limits considered acceptable economic value. Zoledronic acid was generally well tolerated, with a tolerability profile similar to that of pamidronic acid and placebo. As with other bisphosphonates, deterioration of renal function has occasionally been reported in patients receiving zoledronic acid and monitoring of serum creatinine is recommended during treatment. The efficacy of zoledronic acid is therefore well established in patients with hypercalcaemia of malignancy and, for up to 25 months, in the treatment of complications arising from metastatic bone disease in patients with multiple myeloma or solid tumours. The clinical profile of zoledronic acid compares favourably with that of pamidronic acid in patients with cancer and zoledronic acid has a more convenient administration schedule with the potential for better compliance. Thus, zoledronic acid is an effective bisphosphonate and is positioned to play an important role in the management of advanced cancer patients with bone metastases.
PMID: 15161327 [PubMed - indexed for MEDLINE]
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Old 11-15-2006, 07:39 PM   #10
Lani
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putting the thinking cap on...

It may not be possible to do the vertebroplasty at any site that was already irradiated (radiation makes wound healing very slow) but it is unclear how wide the radiation field was (do you know?)

Also, if your mother's kidney function is not tip-top they may feel bisphosphonates are too risky;

Here is an article recommending radiating less times with a higher radiation dose:

ABSTRACT: Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy X 1) versus multiple fractions (3 Gy X 10) in the treatment of painful bone metastases [Radiotherapy & Oncology]
Background and purpose: To investigate whether single-fraction radiotherapy is equal to multiple fractions in the treatment of painful metastases.

Patients and methods: The study planned to recruit 1000 patients with painful bone metastases from four Norwegian and six Swedish hospitals. Patients were randomized to single-fraction (8 Gy x 1) or multiple-fraction (3 Gy x 10) radiotherapy. The primary endpoint of the study was pain relief, with fatigue and global quality of life as the secondary endpoints.

Results: The data monitoring committee recommended closure of the study after 376 patients had been recruited because interim analyses indicated that, as in two other recently published trials, the treatment groups had similar outcomes. Both groups experienced similar pain relief within the first 4 months, and this was maintained throughout the 28-week follow-up. No differences were found for fatigue and global quality of life. Survival was similar in both groups, with median survival of 8-9 months.

Conclusions: Single-fraction 8 Gy and multiple-fraction radiotherapy provide similar pain benefit. These results, confirming those of other studies, indicate that single-fraction 8 Gy should be standard management policy for these patients.
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Old 11-15-2006, 07:48 PM   #11
Lani
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My ruminations...

especially since she lives in Florida

One thought: Get her in a pool. If it is above shoulder height it will mostly likely greatly reduce the force of gravity on her spine and relieve that part of her pain that is from the bone being too weak or the nerves being pinched. If there is something from the metastasis itself causing her pain (chemical rather than mechanical) this may not relieve her pain, but warm water is quite soothing and may give her some emotional relief.

Press her doctor on what pain relief methods may be available--I read about people abusing "fentanyl patches" which were meant for cancer patients. Many of these may be too strong for people of her age, especially if her liver or kidney function are not optimal.

If nothing else, you might ask to try a TENS machine. It works on the principal that, if you stub your toe AND THEN bite your finger, the latter relieves some of the pain of the former, as the brain cannot process two signals approaching it simultaneously from two places very well--it dampens the pain. The electrodes need to be placed between "the pain and the brain" so I guess up below her neck??? A pain specialist or physical therapist may be able to help you.

Again, I am just sharing information not making recommendations. I do
not claim ANY expertise. Just trying to pick my brain to see if I can impart any helpful information.
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Old 11-15-2006, 08:08 PM   #12
Nguyen
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Many thanks for taking the time to share your knowledge!!!

- Nguyen
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Old 11-15-2006, 08:27 PM   #13
skibunny
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Smile Thank you

Lani, thank you so much. Zometa was something my mom's Dr. had mentioned. I will pursue this further.

Skibunny
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Old 11-15-2006, 09:53 PM   #14
Bev
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SkiB, My mom had the cement injection for OsteoP and it did not do the trick. I'm sure there are a ton of variables. It just doesn't always work. I'm glad I came upon this topic and wish I had more to offer. BB
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Old 11-18-2006, 12:46 AM   #15
Lani
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more on zoledronic acid

The Lancet Oncology
Volume 7 • Number 11 • November 2006
Copyright © 2006 Elsevier






Newsdesk
Zoledronic acid palliation in bone-metastatic breast cancer


Bryant Furlow



PII S1470-2045(06)70927-5


Women with painful skeletal-related events (SRE) benefit from second-line zoledronic acid, report researchers (J Clin Oncol, published online Sept 25, 2006; DOI: 10.1200/JCO.2006.05.9212).

Bone is the most common site of metastatic disease in women with breast cancer, frequently causing SRE. A phase II trial of 31 women with SRE and bone disease progression who had received first-line bisphosphonate treatments, showed palliative benefits from zoledronic acid. Women had improved pain control and decreased urinary N-telopeptides, a biomarker of bone turnover, compared with baseline measures.



Appropriate bisphosphonate treatment could save costs

“This study shows that patients with progressive bone metastases or SREs while on clodronate or pamidronate can have palliative benefits with a switch to the more potent bisphosphonate zoledronic acid”, says lead author Mark Clemons (Princess Margaret Hospital, Toronto, Ontario, Canada). “If confirmed in randomised trials, these findings have major implications [for] the use of bisphosphonates.”

“The authors should be commended for giving us information on what to do in a frequent clinical situation”, says Peter Barrett-Lee (Cardiff University, Wales, UK). “Now we have some evidence that switching to a newer, more potent agent might help patients failing on first-line bisphosphonates.”

Many centres already use zoledronic acid as first-line treatment, Barrett-Lee points out. “The new results will not be relevant in such cases”, he notes. “But quite a few [clinicians] still use pamidronate first line.”

“It is too early to draw conclusions about complications, which usually occur later. Physicians should not administer second-line bisphosphonates indefinitely”, comments Meletios Dimopoulos (University of Athens, Greece). Zoledronic acid costs five times more than pamidronate, Clemons notes. “We can use less expensive agents first line and save more costly drugs for patients with progression. Appropriately targeting bisphosphonate therapy to those most likely to benefit could save billions of dollars globally.”
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