Lani's Biospecimen Repository Proposal -- PLEASE READ

[Cynthia]

Friends,

I have been following with great interest the excellent discussions that Lani began about the possibility of creating a Her2+ biospecimen repository. I agree with the observations made by several others – the creation and running of a biorepository is fraught with many, many obstacles. Some of them relate to complex legal issues, consistency of collection practices, lack of annotated clinical data to accompany the tumor samples, privacy issues, Institutional Review Board (IRB) concerns, unwillingness of hospitals to part with samples, and of course – money. Having said that, the National Cancer Institute (NCI) recently announced that the number one impediment to advancing cancer research is a lack of properly collected, well annotated (i.e., with accompanying information about what happened to the person to whom the tumor once belonged), human cancer specimens. I have spent the past year of my professional life focusing (though not exclusively) on how biospecimen repositories work, how they don’t work, and how they could help to advance cancer research if best practices were employed.
<O:p</O:p
I have learned a great deal over the past year, including the following:
<O:p</O:p

1. Researchers/hospitals recognize the value of human tissue for research purposes and don’t want to share freely.


2. There are currently no uniform collection and storage practices.


3. If the NCI had its way and all research institutes were to collect and retain samples in the manner NCI would like, it would be cost prohibitive for the vast majority of biospecimen repositories to comply.


4. NCI has not succeeded to date in collecting the tissue samples from academic institutions across the country it so desperately wants for use in its Cancer Genome project.


5. Many patient advocate groups understand the importance of biorepositories, but due to the costs and complexities, with a few exceptions (e.g., the Multiple Myeloma Research Consortium Tissue Bank), patient groups have not successfully stood up meaningful repositories on their own.


Thus, I think that Lani has proposed a truly unprecedented approach to creating a biorepository dedicated to Her2+ tissue samples. In a number of ways that I would be happy to address in a later posting, I believe that what Lani proposes differs from any other repository now in existence in this country (and probably in the world). Thus, I suggest that if we undertake this effort we, as the donors, insist that our tissue be given not to a research facility that will keep it solely for its own use (no matter how promising or earnest that facility’s research efforts appear), but rather to a facility that will serve primarily in the role of honest broker. By this I mean the recipient of our samples and medical information should be tasked with allowing the information derived from the samples, and at times the samples themselves, to be used by researchers around the world who demonstrate that the samples and data will be put to the highest and best scientific use. Thus, all applications for samples and data must be vetted by an independent scientific review board that meets frequently (i.e., virtually) and that allows only proposals with strong scientific merit to access actual samples – though digital data can be more freely shared since digitalized data do not diminish in size. Additionally, I suggest we insist that there always be at least one, if not more, of us on the oversight board to keep everyone honest.

<O:p</O:p
I waited until now to weigh in on the discussion because I wanted to ask around to see if there is strong interest from the medical side in doing something like Lani proposes. I had a very promising meeting yesterday with the director, head pathologist and senior research nurse of what I have been told is probably the best and largest breast biorepository in the world. I am informed that while Lani’s project could result in a great deal of work and expense, it could produce something of great and truly unique value to the cancer research community at large. Thus, as a precursor to further discussions, I have been asked to obtain some information from those of you who might be interested in donating some or all of your tumor blocks. (By the way, I understand that once personal information is obtained from you as a part of the donation process, all of your samples and corresponding medical records and history would be de-identified so that no one doing research within the repository would be able to identify you. More information on this and many other points will follow if we proceed with this.)

<O:p</O:p
Thus, if you are inclined to donate your tumor block to this type of a project, would you please answer the following questions in a reply post:
<O:p</O:p

1. Please state the name and location (i.e., city and state) of the hospital that likely retains your tumor block.

2. Please indicate if you have copies of (and would be willing to provide them if asked) the following medical records:

a. Your surgical report(s)


b. Your pathology report(s)


c. Your cancer treatment records (e.g.., oncology, radiation therapy)


3. If you don’t have copies of the records referenced in Item 2 above, would you be willing to obtain copies of them from your hospital/physician and send them in?

4. Would you be willing to respond to a detailed online questionnaire about your history, your habits, etc.?


5. Would you be willing to be interviewed by a research nurse by telephone?


Once I receive ample responses to the above, I will meet again with the principal investigator to discuss at greater length his level of interest, likely impediments, etc. If there is enough interest on his and our end to move forward, I would certainly disclose to you at that time the identity of the facility in question, more details on the proposed structure, and everything else you care to know.
<O:p</O:p

Please understand that I have absolutely nothing to gain financially from this endeavor. If we can pull this off, rest assured I will donate my tumor block and personal information. Thus, I am pursuing this for the same reason all of you are – because we all want to help advance a cure for this dreadful disease.
<O:p</O:p

Thank you and stay well.
<O:p</O:p

Cynthia
<O:p</O:p

[Lolly]

Cynthia, here's my information. Thank you for taking the time and using your knowledge to further this cause. It will be a wonderful thing if this happens!

1.Providence St.Vincent Hospital, Portland, OR.
2-5. Yes

[AlaskaAngel]

Cynthia,

It is exciting to see yet another person with knowledge in this area working through the complications to make a HER2 registry a reality.

I am interested in knowing whether you or your research contacts consider the worldwide renowned researchers involved in the TEACH trial to be a collective group such as the one you propose would be involved in a registry for HER2 samples.

The TEACH clinical trial is made up solely of HER2 tumor samples and medical histories from patients around the world. Granted, it involves only those who have done chemotherapy and have never had Herceptin. However, as I understand it, all of these samples are from tumors collected prior to any treatment. They may be all the more valuable in that they were collected from trial participants who at start of trial are all NED even years out from treatment. Can we learn from this set of already collected worldwide HER2-only samples in any way, or not, in working toward our goal?

AlaskaAngel

[Audrey]

Cynthia, I would be happy to contribute to this repository effort--my treatment/records are all at the Cleveland Clinic. "Yes" to all the other questions.

[Becky]

Hunterdon Medical Center, Flemington, NJ

Yes to all other questions.

Thank you in advance for your efforts on this worthwhile project.

[Jean]

Cynthia,
It was so nice to meet you at the SABCS.

Weill Medical College of Cornell University/New York Presbyterian Hospital
Yes, to all questions.

Kind Regards,
Jean

[mslinda]

Thank you Cynthia for what you are doing.

Wesley Medical
Hattiesburg, MS
Yes to all the other questions.

Thanks,
Linda Nance

[sassy]

Twin County Hospital, Galax, Virginia
Wake Forrest University Baptist Medical Center, Winston-Salem, North Carolina

Yes to all questions.

The potential with this is tremendous.

[lilyecuadorian]

Carolina Medical Center at Charlotte, North Carolina

and Yes to all the questions

thanks
Lily Schachner

[Lani]

ongoing) It has accumulated 1000 her2+ patients with Stage IV(metastatic) her2+ breast cancer and is evaluating their specimens (both primary and metastatic, when available) and their progress with various treatments.

What hasn't been done is to look at all her2+ patients, in ALL stages, with a registry and access to all records/tests/imaging.

Cynthia, I salute you for bringing this project forward and especially for trying to make the registry less like a business and more like a "lending library"

The information to be gleaned is far too important for researchers to hoard (sort of like governments hoarding bird flu samples)

I selected a few abstracts to show just how helpful the registHer trial has been so far, and its results are not even due out until 2009!

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 20095
Author(s):
P. Kaufman, M. Mayer, S. Paik, M. Ulcickas Yood, D. Yardley, E. Tan-Chiu, A. Brufsky, H. Rugo, D. Tripathy, L. Wang
Abstract:
Background: HER2 is amplified in 25% of breast cancers and is associated with poor survival. registHER captures the natural history, treatment patterns and outcomes in 1000 newly-diagnosed HER2-positive MBC patients (pts)throughout the U.S. This observational study recruits pts in both academic and community centers. Methods: This ongoing prospective cohort study collects clinical, pathologic and treatment data at enrollment, quarterly until death, loss to follow-up or 3 years after the last enrollment. We describe baseline pt and clinical characteristics in registHER compared with HER2-positive MBC pts in the phase III pivotal trial (Slamon DJ, et al. N Engl J Med. 2001;344:783-792). Results: Between December 2003 and September 2005, 813 eligible pts were enrolled at 280 study sites. Most pts were seen at community-based (76%) vs academic (18%) clinics; a few pts did not fall into either category (6%). A comparison of baseline characteristics is shown below. Conclusions: registHER pts tended to have a shorter disease-free interval and more estrogen receptor positive disease than pts in the pivotal trial. Reasons for these differences could reflect trial referral and/or diagnostic testing differences. Fewer registHER patients were white, but other characteristics were similar between the two groups. These findings support the hypothesis that observational studies describe a broad patient population which may not exactly duplicate clinical trials. Within registHER, there was some variation between academic vs community clinics (eg. nodal status and adjuvant therapy). Treatment pattern analyses are ongoing.


Baseline
Characteristics
Academic registHER
(N = 142)
Community registHER
(N = 619)
Pivotal Trial*
(N = 469)
Age, median years (range)
50 (26-81)
55 (21-92)
53 (25-77)
Race
White, n (%)

112 (79)

509 (82)

422 (90)
Disease-free interval, n
Median months
142
15
613
18
464
22
Nodal status at initial breast cancer diagnosis, n
Positive, n (%)
76
56 (74)
357
243 (68)
402
269 (67)
Hormone receptor status, n
Estrogen-positive, n (%)
142
79 (56)
586
313 (53)
464
190 (41)
Prior adjuvant chemotherapy, n
Yes, n (%)
142
50 (35)
619
263 (43)
**
**

Continued Use of Trastuzumab (Herceptin) after Progression on Prior Trastuzumab Therapy in HER-2-Positive Metastatic Breast Cancer
Authors: Pusztai, Lajos1; Esteva, Francisco1
Source: Cancer Investigation, Volume 24, Number 2, March 2006 , pp. 187-191(5)
Publisher: Taylor and Francis Ltd




Key: - Free Content - New Content - Subscribed Content - Free Trial Content


Abstract:
Whether to continue trastuzumab after objective evidence of disease progression or not is an important unanswered clinical question for women with metastatic disease. This question is also relevant for those who relapse after adjuvant trastuzumab-containing therapy. Unfortunately, there is little evidence to guide decision-making. The modest toxicity and the possible, but unproven, benefit from the continued use of trastuzumab may account for the currently wide spread practice of continued administration of this drug after progression. However, there is no convincing evidence to support the use of extended trastuzumab therapy after progression. At least two randomized trials with no trastuzumab in the control arms were attempted but failed to accrue patients. In the absence of results from a randomized clinical trial, a central registry program that collects information longitudinally from a large number of patients with HER-2 positive breast cancer during the course of their disease was initiated (RegistHER, www.registher.com ) to learn about the long term side effects and benefits of prolonged trastuzumab therapy. The anticipated introduction of second generation HER2-targeted agents into the clinic also raises a new question; will switching to these agents be more effective than continuation of trastuzumab? Clinical trials are currently planned to address question prospectively.

Keywords: Trastuzumab; Metastatic breast cancer; Targeted therapy
Document Type: Research article
DOI: 10.1080/07357900500524629
Affiliations: 1: Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Survival After Breast Cancer Brain Metastases About 13.9 Months: Presented at SABCS
By Ed Susman

SAN ANTONIO, TX -- December 17, 2007 -- Researchers mining the dataset from the registHER study -- an observational cohort of about 1,000 women with HER2-positive metastatic breast cancer -- reported that the median survival after detection of brain metastasis is about 13.9 months.

The researchers also found that brain metastases occur in about 30% of women, and also occur relatively early -- after a median of 12.1 months following the diagnosis that the cancer has spread, said Denise Yardley, MD, Director, Breast Cancer Research Program, Sarah Cannon Research Institute, Nashville, Tennessee.

"RegistHER represents the largest dataset of patients with HER2-positive metastatic breast cancer and provides a unique opportunity to characterize the natural history of this important subset of patients," Dr. Yardley said on December 16 here at the 30th Annual San Antonio Breast Cancer Symposium (SABCS).

The study enrolled 1,023 women between December 2003 and February 2006. Dr. Yardley's team analyzed 768 of these women, who were diagnosed with metastatic disease. Of this group, 236 women (30.7%) were diagnosed with central nervous system metastases.

These HER2-positive patients who developed central nervous system metastases were more likely to be young, to have hormone-receptor-negative disease, and to have higher disease burden, Dr. Yardley said.

About 39.7% of the patients were on their first line of chemotherapy when they were diagnosed with central nervous system metastases; 32.1% were on their second line of treatment; 16.8% of patients were into their third line of treatment.

Among patients who had a central nervous system metastases at the time of diagnosis, about three fourths had a trastuzumab-containing first-line regimen; 5.8% of these women received a chemotherapy- or hormone-containing first-line treatment; 17.3% did not receive a first-line treatment but were receiving treatment before their first progressive event.

Funding for this study was provided by Genentech, Inc.


Presentation title: RegistHER: Patient Characteristics and Time Course of CNS Metastases in Patients With HER2-Positive Metastatic Breast Cancer. Abstract 6049



Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 670
© 2005 American Society of Clinical Oncology

This Article
Abstract

registHER: A prospective, longitudinal cohort study of women with HER2 positive metastatic breast cancer

E. Tanchiu, P. A. Kaufman, S. Paik, M. Ulcickas-Yood, M. Mayer, D. Tripathy, H. Rugo and A. Brufsky
Cancer Research Network, Plantation, FL; Dartmouth Hitchcock Medcl Ctr, Lebanon, NH; NSABP, Pittsburgh, PA; Episource LLC, Hamden, CT; Patient Advocate, New York, NY; Univ of Texas Southwestern Medcl Ctr, Dallas, TX; Univ of CA San Francisco, San Francisco, CA; Univ of Pittsburg Cancer Institute, Pittsburgh, PA

670

Background: Human Epidermal Receptor 2 (HER2) is gene amplified in approx 25% of patients with breast cancer and is an unfavorable prognostic factor for survival. Both NCCN and ASCO recommend that all breast tumor samples be tested for HER2 status by either immunohistochemistry (ICH) or fluorescent in situ hybridization (FISH). Methods: RegistHER is a prospective, longitudinal cohort study of HER2 positive MBC designed to understand treatment practice and outcomes. Eligible patients are HER2 + with MBC diagnosed within 6 months and receive treatments according to standard of care. HER2 testing data collection includes tissue source (primary vs metastatic tumor) and test Method: All treatment information is collected from the time of initial diagnosis to study discontinuation or death. Study endpoints include time to treatment failure, time to progression, tumor response, cardiac safety and survival. All data are obtained through an internet-based data collection system. Results: 273 of 291 eligible patients have been enrolled over 11 months, of a planned n=1,000. Patient characteristics: median age 54 yrs (range 22 - 91), race (white 83%), PS 0–1 64%, DFI 20 mos (range 0 - 263 mos). Tumor characteristics: ER and/or PR + 46%, ductal histology 86%. HER2 testing results were available in 264 patients. The tissue source for HER2 testing was primary tissue samples only (67%), metastatic tissue only (13%) or both 17%. Positive HER2 results were considered to be either IHC 3+ or FISH positive in >90% of patients. In those with results from both primary and metastatic tissue sources (n=46), HER2 results were confirmed by the same testing method in 23/46 (50%). IHC results were confirmed by FISH in 11/46 (24%). Discordant HER2 results (discrepant IHC-IHC or IHC- FISH results) between primary and metastatic tissue samples were reported in 7/46 (15%). Conclusion: The pace of enrollment suggests that this study design represents a feasible approach in HER2+ MBC. The predominant HER2 test reported was IHC performed on primary tissue samples. The number of patients with confirmatory metastatic biopsy findings and discrepant HER2 results was higher than anticipated and highlight the importance of accurate HER2 testing practices.

[AlaskaAngel]

Hi Lani and Cynthia,

I agree, having an entirely separate database containing all HER2s is the goal. I'm asking whether there is any reason to examine or consider what went into creating the legal and practical aspects of those already-existing HER2 databases, as well as any possibility of accessing and utilizing any of the basic data already collected in those databases (1,000 as you mentioned for metastatic HER2's and in the case of the TEACH trial, more tumors obtained prior to initial treatment for several thousand early stage HER2's who have never had Herceptin but have completed chemotherapy and are NED). Even just using the TEACH trial example to consider what went into the establishment of the international advisory panel of HER2 oncologists, or the way in which they established the specifics for their tumor collection, could be helpful in creating our general HER2 registry. Does that not make sense? Or is the raw data from tumors and histories (not the conclusions from ongoing trial study) as well as the structure that those two trials have put together entirely inaccessible and/or completely useless to us in our efforts?

AlaskaAngel

[RhondaH]

GREAT research for such an important need.

I would GLADLY participate.

Spectrum Health-Downtown, Grand Rapids, MI
Yes to all.

Rhonda

[Kimberly Lewis]

Duke University Hospital, Durham, NC
I have my slides too if that helps.
Yes to all questions. Thanks for considering this..

[Sheila]

St Mary's Hospital Streator, IL
Rush University Medical Center Chicago, IL
Yes to all the questions

[lisajones4]

Yes to all!!!

[Margerie]

Sierra Vista, San Luis Obispo, CA

Yes to all. I have my slides.

[Cathya]

Ottawa Regional Cancer Centre, General Division, Ottawa, Ontario Canada

I believe they have everything and yes to the other questions. I would also be happy to approach the hospital through my doctor and ask for the same from other her2+ bc patients. Perhaps they would allow me to post a request for these patients in the Cancer Centre. Could we all do this at our hospitals?

Cathy

[madubois63]

Wow, I started crying when I read this thread. How exciting!!! YES to all the questions. I have slides from prior to all chemo/radiation, slides from after chemo/radiation but before Herceptin and slides from after chemo/radiation/Herceptin. The later slides are still being used, and I am (STILL) waiting for the final Fsh report. I also have bone marrow biopsies available. Every thing is located in NY (3 different locations), but I am more than willing to get everything needed!!!!!!!!!!!

[tdonnelly]

Hi Cynthia,
I too am interested in helping any way that I can regarding HER2 Project. My surgical site was: Little Company of Mary Hospital,Evergreen Park, IL however FISH report came from Mayo Clinic, Dept. of Lab Med & Pathology, 200 First Street Southwest, Rochester MN 55905. Who has my sample??? How long are the samples kept? My answer is YES to all your questions. Please contact me at my email address for any further info. Thanks. tld0042@Yahoo.com
Tamara
Invasive Ductal Carcinoma 11/2006 HER2+

P.S. My first thought after dx was the importance of keeping my medical records open to all family members as I am the first in my large extended family with this disease.

[penelope]

Yes to all questions.

UCSF medical center.

[hutchibk]

Cynthia - I get chills thinking about being involved in something so vitally important. Thanks to you, Lani, Joe and Christine for this idea getting wings!

Austin, TX...
St. David's Hospital
and
Seton Hospital

yes to all questions.

Brenda

[Soccermom]

MDAnderson,Houston TX

Yes to all questions!

Thank you for all your hard work,

Marcia

[Emelie]

St Louis Cancer and Breast Institute - St Louis MO
Yes to all of the questions.

[Brenda_D]

I'm not positive, but I think mine are at St. John's Hospital, Springfield,IL.
I can try to get them.
I have have some documentation and could try to get the rest.

[KellyA]

Memorial Health University Medical Center, Savannah, Georgia.
YES!!!!! to all other questions!

Love, Kelly

[Monica]

Great effort!
Saint Peter's University Hospital
New Brunswick, NJ
Yes to all other questions.

Best,
Monica

[StephN]

I have my tumor blocks that I picked up directly from the lab about one year ago. They have documentation regarding that pickup. The lab still has the slides. University of Washington may have a few slides since they did a second review. I would have to check.

YES to the other questions. My interview might take a while due to my ongoing history!

[rinaina]

Evanston/Northwestern Hospital in Evanston Illinois
Yes to all other questions.

[Bev]

Innova Fairfax, VA. Yes to other questions. This is very complex. Thanks all. Bev

[LAURIE]

Massillon Community Hospital (Affinity Medical Center), Massillon, Ohio

yes to all questions

[atdec05]

Thank you for spearheading this. Yes!

- Anna

[Patricia]

California Pacific Medical Center, San Francisco, CA
Yes to all other questions.

[MDW]

Johns Hopkins; yes to all. Thank you to all who are leading the way on this.

[fauxgypsy]

Baptist Hospital, Oxford, MS
Yes to all

Leslie

[dhealey]

Lexington Memorial Hospital, Lexington, North Carolina/North Carolina Baptist Hospital, Winston-Salem, North Carolina and yes to all the questions.
I am very excited about this project. Great work!

[murph]

Pennslyvania hosp. Phila. Pa

Yes to all questions.........thank you in advance ladies!!!

[lexigirl]

Kaiser Sacramento.

Yes to all the questions.

Lexi

[SoCalGal]

Cedars Sinai, Los Angeles - primary tumor
UCLA - recurrance
Yes to all questions.

(PS - the chemo records are called your "flow chart" and my 11 year record was only about 5 pages - very faxable).

Our collective energy and desire to make a difference will make this happen!

[Kim in CA]

Thank you for your efforts Cynthia.

Santa Rosa Memorial Hospital. Santa Rosa, CA

UCSF for surgery for recurrence to liver (however path reports indicated no cancer found, only scar tissue)

Yes to all other questions.

Kim

[DonnaD]

I've got the shivers!

Rush University Medical Center, Chicago, IL
YES

[Montana]

Kalispell Regional Medical Center, Kalispell, Montana.
Yes, to all questions.

[dchips1]

Banner Desert Medical Center, Mesa, Az
Also I had a bx of liver tumour from a met at Banner Baywood , Mesa, AZ
All the others are yes too
thank you
Happy New Year

[DEBBIE S]

Would do what ever I can to be a part of this .... Think your idea is great and would benefit many for years to come ....

Fairfax Hospital, Virginia - Breast
Alexandria Hospital, Virgina - Liver biopsy

Answer yes to all the questions ....

God Bless,

Debbie S.

[Vi Schorpp]

Cleveland Clinic, Independence, Ohio
Yes to all.

[TSund]

Hello. I'm just so impressed. We are happy to share what we can. YES to all questions, Baylor Hospital, Dallas, TX

Q: Ruth had a needle biopsy of original large tumor, and very fortunately had a very good response to pre-operative TCH chemo to the point of only having scattered microscopic cells show positive post-surgery. Therefore I suspect there is no "tumour block" persay? I'm feeling a bit ignorant: Can lots extra slides be made from original needle biopsy speciman?

Kudos to you all in this important project!

Terri

[Lani]

New Year's bustle...

[Mgarr]

Providence Hospital, MI

Yes to remaining questions.

Mar

[Cynthia]

Friends,

Thanks to all who replied. I am bumping this up in the hope of keeping it alive.

Thanks much.

[Faith in Him]

Kaiser Hospital, Fremont Ca
Yes to all other questions.

[jones7676]

Marquette General Hospital, Marquette MI
Northwestern Memorial Hospital, Chicago IL
YES YES YES YES

[cmljungren]

Miami Valley Hospital, Dayton Oh
Yes to remaining questions.

[Emmasmom2]

Yes to all questions.

Northwestern Memorial Hospital, Chicago, IL

[MJo]

Helen Graham Cancer Center
Christiana Medical Center
Wilmington, Delaware

Yes to all

[lilyecuadorian]

I just bring this up .....please Let's Don't forget !!!

[lilyecuadorian]

me again ..please don't miss...

[Jackie07]

Scott and White Hospital
Temple, Texas

Yes