The Breast Cancer Intergroup of North America (TBCI) Correlative Sciences Committee is charged with fostering and reviewing proposals from laboratory and clinical investigators wishing to use Intergroup specimens in correlative studies addressing questions of prognosis and prediction in patients with breast cancer.

Chaired by Dr. Daniel F. Hayes of the University of Michigan, this Committee consists of representatives from each TBCI-member Cooperative Group (ACOSOG, CALGB, ECOG, NCCTG, NCIC CTG, and SWOG), as well as from Groups from outside TBCI (including NSABP and RTOG), and representatives from the National Cancer Institute (NCI).

TBCI has performed a number of prospective clinical trials addressing fundamentally important questions regarding the therapy of breast cancer. The principal questions addressed in these trials have been focused on issues related to adjuvant systemic therapy, although trials of patients with metastatic disease and trials regarding surgery and radiation have also been conducted.

For many of TBCI's trials, prospective collection of tissue from participating patients was built in, although not mandated. These tissues are all formalin-fixed, paraffin-embedded (FFPE), and they are either in the form of a tissue block or cut, unstained sections on glass slides. In some cases, tissue microarrays (TMAs) have been constructed using these tissues.

Since most TBCI trials are definitive randomized, controlled phase 3 trials, the specimen collections developed from these trials strongly lend themselves to correlative studies seeking to test and validate hypotheses. Given the highly annotated nature of these specimens, including the carefully collected patient outcome and other clinical data with which they are associated, the Committee will give priority to validation studies of pre-existing hypotheses supported by data from previously performed pre-clinical and/or preliminary clinical studies. Preliminary data, including assay validation, are required. Exploratory studies without preliminary data will be denied.

It is recognized that exploratory studies are necessary to generate the preliminary data required above. Investigators planning exploratory studies are encouraged to apply to other NCI-supported specimen resources that are more appropriate to these types of studies, such as the Cooperative Human Tissue Network (CHTN) and the Cooperative Breast Cancer Tissue Resource (CBCTR).

Proposals will be rigorously reviewed by the Committee for scientific merit. Every proposed marker must be well supported by background data for both the data supporting the proposed hypothesis as well as evidence that the assay works in the types of specimens TBCI has banked (principally, formalin-fixed, paraffin-embedded tissues). The proposal should also be precise about assay methods and the number of slides needed to complete each study. Finally, methods for statistical analysis should be described for each marker, including an estimate of the percentage of patients who will be "positive" or "negative" and the estimated magnitude the investigator expects to see in outcomes between the two, accompanied by power estimates of the odds of observing this estimate.

Each marker will be reviewed on its own merit. If multiple marker studies are proposed in a single proposal, the investigator should clearly provide the above information for each marker, since inconclusive assessment by the Committee for one marker could lead to the entire proposal being disapproved.

In an effort to expedite investigator access to Intergroup specimens, the Cooperative Group Chairs and NCI have agreed that all specimens collected from an Intergroup clinical trial should be stored at the bank of the Cooperative Group leading the clinical trial. Every effort will be made to retrieve existing samples from collection sites/participating Groups for long-term, central storage at the Lead Group's bank, to facilitate the acquisition of Intergroup specimens by investigators with worthy study proposals.

Please see the listing of specimens available from closed TBCI trials as well as the listing of active TBCI trials (specimen collection is still underway on most of these active trials).

Instructions to Investigators/FAQs

Which specimens are available from TBCI?
How may I apply to use these specimens?
Who are the main contact people for the TBCI Correlative Sciences Committee?
How often will proposals be reviewed?
Which correlative science proposals should be submitted to an Intergroup Correlative Sciences Committee, and which to CTEP?
Is the investigator required to discuss his/her correlative science proposal with the Group that led the clinical trial from which specimens are requested?
When can proposals for funding be submitted? How will approved studies be funded?
Should investigators planning to submit a proposal for internal review do so before submitting it to the Intergroup Correlative Sciences Committee?
Is Committee approval required for tissue-microarray (TMA) construction or for standard ER/PgR/HER2 assessment using TBCI TMA's?
Can a single correlative science proposal request specimens from more than one Intergroup trial, perhaps led by different Groups?
Can any investigator propose?
May I present my proposal to the Committee?
What kind of preliminary data are required?
How should statistical design be approached?
Once the Intergroup Correlative Sciences Committee approves a proposal, what next?

Which specimens are available from TBCI?

Please see the listing of specimens available from closed TBCI trials as well as a listing of active TBCI trials (from which specimens are still being collected).

How may I apply to use these specimens?

Investigators must submit their proposals using the TBCI Correlative Science Proposal Submission Form. Proposals should be emailed to the Protocol & Information Office (PIO) of the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) at email pio@ctep.nci.nih.gov. The Committee accepts only electronic submissions.

Who are the main contact people for the TBCI Correlative Sciences Committee?

Inquiries regarding funding and new ideas for studies, including appropriate specimen collections, should be directed to:

Daniel Hayes, M.D.
Chair, Correlative Sciences Committee of the Breast Cancer Intergroup of North America
Phone: 734-615-6725
Fax: 734-615-3947
Email: HayesDF@umich.edu

Proposals should be submitted to:

Protocol & Information Office
Cancer Therapy Evaluation Program
National Cancer Institute
Email: pio@ctep.nci.nih.gov
Only electronic submissions are accepted.

Inquiries regarding funding may be directed to either of the following:

How often will proposals be reviewed?

Applications are accepted on a rolling basis. Investigators should expect notification of the Committee's decision on a proposal within six (6) weeks of submitting the proposal to the Committee. Depending on circumstances, investigators who require an expedited review outside review deadlines can request such an expedited review.

Which correlative science proposals should be submitted to an Intergroup Correlative Sciences Committee, and which to CTEP?

Intergroup Correlative Sciences Committee review: Stand-alone correlative studies (i.e., studies not embedded in a clinical trials protocol) proposed after submission of the Intergroup clinical trials protocol to CTEP are subject to review by the Intergroup Correlative Sciences Committee. (This holds true for studies proposing to use a subset of < 100 samples from the Intergroup trial, since depletion of a subset of samples from the larger dataset could severely limit the utility of the entire dataset.) Investigators do not have to be Group-affiliated to propose a stand-alone correlative study to the Intergroup Correlative Sciences Committee.

Intergroup Correlative Sciences Committee and CTEP review: If, however, a new correlative study is proposed for embedding within the protocol following submission of the clinical trial protocol to CTEP, this would necessitate a protocol amendment that should be reviewed first by the Intergroup Correlative Sciences Committee, to ensure Intergroup support, and then by CTEP. During its review, CTEP will take into consideration the Intergroup?s review.

CTEP review: If a correlative science study is embedded within the clinical trial protocol at the time of initial submission to CTEP, CTEP will review the study. Intergroup support should have been obtained during the protocol's development. The embedded correlative study will not undergo review by the Intergroup Correlative Sciences Committee.

CTEP review: Amendments to correlative studies that were embedded within the protocol at the time of initial submission to CTEP should be submitted to CTEP. They are not subject to review by the Intergroup Correlative Sciences Committee.

Note: Usually, a trial is considered an Intergroup trial if it involves at least two Groups (i.e., a Lead Group and an endorsing Group). The best way to determine which trials are Intergroup trials in your disease area of interest is to visit the Web site of the appropriate disease-specific Intergroup.

Is the investigator required to discuss his/her correlative science proposal with the Group that led the clinical trial from which specimens are requested?

Investigators with a new correlative science proposal are strongly encouraged to discuss their proposal with the Cooperative Group that led the trial from which they are requesting specimens, in order to better understand the clinical trial and to develop statistical analysis plans. In this regard, the Committee Chair or lead CIB representative can guide investigators to the appropriate individuals within this Lead Clinical Group. Review and endorsement of the proposal by the Lead Clinical Group is recommended.

However, investigators can submit a correlative science proposal to the Committee independently.

When can proposals for funding be submitted? How will approved studies be funded?

Funds may be available from the Committee to defray costs of approved studies. For additional information on these funds, please contact Dr. Daniel Hayes at hayesdf@umich.edu or phone: 734-615-6725.

Application to potential funding sources other than the Committee (for example, grant applications) should be submitted only after approval from the Committee has been obtained. Although the Committee encourages grant proposals requesting funding to perform studies using Intergroup material, investigators are discouraged from submitting for potential funding until and if the proposal is approved by the Intergroup Correlative Sciences Committee. The Committee will not provide "provisional" letters of collaboration. Rather, it will provide letters of collaboration when (and if) Committee approval is granted.

In consideration of grant deadlines, Intergroup Correlative Sciences Committees will try to be as responsive and rapid as possible in reviewing proposals. Every effort will be made to notify investigators of the Committee's decision on their proposal within six (6) weeks of their submitting the protocol to the Committee. Depending on circumstances, investigators who require an expedited review outside review deadlines can request such an expedited review.

Once a proposal is approved by an Intergroup Correlative Sciences Committee, investigators are encouraged to submit approved proposals to funding entities of their choice to obtain peer-reviewed funding for the study.

Investigators are requested to discuss funding submissions with either the Committee Chair or lead CIB representative before submitting to a potential funding source. This will help to ensure that appropriate subcontracts (such as for biostatistics) are developed to help defray study costs.

For high-priority, approved studies, if an investigator cannot obtain peer-reviewed funding, every effort will be made to help cover the costs of specimen preparation and shipping.

Should investigators planning to submit a proposal for internal review do so before submitting it to the Intergroup Correlative Sciences Committee?

Yes. Investigators planning to submit their correlative science proposal for internal review by their own Cooperative Group/institution are asked to please do so before submitting to the Intergroup Correlative Sciences Committee. In this way, all recommendations from the internal review can be incorporated into the proposal by the time the Committee receives it.

Investigators are also encouraged to seek the review and endorsement of the Cooperative Group that led the clinical trial at this time, although this is not necessary for submission of the proposal to the Committee.

In other words, the Intergroup Correlative Sciences Committee should see the "best and final" version of the proposal.

Is Committee approval required for tissue-microarray (TMA) construction or for standard ER/PgR/HER2 assessment using TBCI TMA's?

Scientific approval by the Committee is not required for the lead Group to construct a tissue-microarray (TMA) from TBCI blocks or to perform standard ER, PgR, or HER2 assessment using those TMA's. Committee approval is required, however, for any other type of correlative analyses that would use TBCI TMA's. Recommended assays for standard ER, PgR, HER2 assessment include the following:

ER:
IHC: SP1 or 1D5

PgR:
IHC: Pg6/636 Dako

HER2:
IHC: Herceptest or Cb11
FISH: Pathvysion® or Dako pharmDx™

Can a single correlative science proposal request specimens from more than one Intergroup trial, perhaps led by different Groups?

If investigators are requesting to use specimens from multiple trials but believe that a single proposal submission would be appropriate for their correlative science proposal, they may submit a single proposal. However, they should provide clear scientific rationale justifying why they are requesting samples from different trials - for example, they might request samples from two studies, by different Groups, that addressed the same therapeutic questions.

Can any investigator propose?

Investigators do not have to have Cooperative Group affiliation in order to propose a study. Correlative science proposals are welcomed both from investigators who are affiliated with a Cooperative Group and from those who are not. Foreign investigators are also welcome to propose.

Investigators representing industry should establish an industry-university collaboration with one of the Cooperative Groups, in which a Group-affiliated co-P.I. would also be appointed, in addition to the industry P.I.

Only those investigators who have had/will have substantive input into the design, development, and/or conduct of the proposed correlative science should be listed as co-investigators on the correlative science proposal. Correlative science proposals do not have to have the same kind of Intergroup representation as required for Intergroup clinical trials.

May I present my proposal to the Committee?

Yes. Before each review, there will be an optional open session during which investigators are invited to present their proposal and take questions from the Committee, if they so choose.

What kind of preliminary data are required?

Proposals are encouraged for the study of markers for which preliminary data exist to support the hypothesis that there might be an interaction between the marker's results and treatment outcomes.

At the least, the investigator should provide preliminary data showing that the reagents perform well in formalin-fixed, paraffin-embedded (FFPE) tissue (for those studies involving solid tissue) and that the assay is reproducible. Furthermore, (for those studies involving solid tissue) preliminary studies used to support the hypothesis should have been performed in FFPE tissues from patients for whom outcomes are known. These studies should be used to generate preliminary hypotheses regarding whether the marker in question is prognostic, or might have predictive interactions with the therapeutic questions addressed in one or more of the Intergroup's clinical trials.

For example, an application requesting use of specimens from an Intergroup trial addressing taxane therapy would be favorably viewed if its hypothesis is supported by preliminary data suggesting that the proposed marker may predict resistance to taxane therapy.

Given the highly annotated nature of Intergroup clinical trial specimens, including the carefully collected patient outcome and other clinical data with which they are associated, the Committee will give priority to validation studies of pre-existing hypotheses supported by data from previously performed pre-clinical and/or preliminary clinical studies. Exploratory studies lacking preliminary data will be denied.

How should statistical design be approached?

Although statistical analysis of the proposed studies will require input from the respective statistician of the Cooperative Group that led the trial from which specimens are requested, the exact nature and extent of collaboration between the researcher and the statistical office of the lead Group is left to the individuals to define, and can certainly vary depending on the study.

Obviously, statistical power will be limited by the number of samples available and the number of events that have occurred in the clinical trial, and will also be affected by the established cutoff values defining the relative distribution of "positives" and "negatives" and the expected differences in outcomes predicted by the marker results. These assumptions and estimates will need to be made from the preliminary studies that are expected to be cited in the proposal submission.

Once the Intergroup Correlative Sciences Committee approves a proposal, what next?

Once a proposal is reviewed by the Committee, the investigator will be sent the consensus decision of the Committee in a 'consensus review' document. The consensus review will indicate the revisions requested by the Committee, or if the proposal has been disapproved. If comments requiring a response are contained in the consensus review, the investigator will have to submit a revised proposal that may or may not have to undergo full Committee re-review. The review chair will determine if a revised submission must undergo full Committee re-review or if only an abbreviated re-review is required.

Once the investigator receives word that his/her proposal has been approved by the Committee, notification that the correlative study has received scientific approval from the Intergroup Correlative Sciences Committee will be sent to the appropriate individuals within the Groups that participated in the clinical trial. These individuals will include the relevant banking personnel as well as Group and disease committee leadership.

Approval by an Intergroup Correlative Sciences Committee pertains only to scientific review. Therefore, following approval of a correlative study by the Intergroup Correlative Sciences Committee, the proposing investigator is still responsible for going through the usual steps of reaching an agreement with the Cooperative Group that led the clinical trial from which specimens are requested, securing IRB approval for the proposed work (i.e., approval from the investigator's local IRB, as well as the local IRB of any co-investigator who will be receiving and running assays on the specimens), obtaining funding, and so forth.

Principal Investigators of studies approved by the TBCI Correlative Sciences Committee will be required to submit administrative data from the study to the NCI via the Abbreviated Clinical Data Update System reporting mechanism; submit brief, periodic progress reports; and, once the primary analysis of the study is published, send specific data sets (i.e., at the patient level) from the correlative study to the Cooperative Group that led the clinical trial. Any publication of the study should be sent to the TBCI Correlative Sciences Committee, for their information, with appropriate acknowledgments (e.g., the Group that led the trial).

The requested specimens will be reserved for the investigator's use for one (1) year following study approval. If funding has not been secured for the study by that time, the investigator will be required to re-submit his/her application to re-request the specimens.

Summary of specimens available from TBCI closed trials

(For a listing of active TBCI trials in which specimen collection is still underway, please see the TBCI active trials listing on the TBCI Home page.)

The numbers of specimens listed below are as of September 2004. If you need the most up-to-date numbers of specimens available from a TBCI trial, please contact the specimen bank of the Group that led that trial.

Specimens in addition to those listed below: Cells and DNA are stored at ECOG from E2190. Plasma is stored at CALGB from C9741, CALGB-9344, E5188, E-EB193, SWOG-8814, SWOG-9313.

Clinical trial protocol number	Title	Study arms	Protocol description (PDQ)	Approx # cases with usable blocks in TBCI banks	Approx # cases with usable unstained slides	TMA?	Specimen submission specified by protocol	Patients accrued	Groups storing specimens
C9741	Phase III Randomized Study of Sequential Chemotherapy Using Doxorubicin, Paclitaxel, and Cyclophosphamide or Concurrent Doxorubicin and Cyclophosphamide Followed By Paclitaxel at 14 and 21 Day Intervals in Women With Node Positive Stage II or IIIA Breast Cancer	Arm I: Sequential A, paclitaxel, C, Q3W Arm II: Sequential A+ G-CSF, paclitaxel + G-CSF, C + G-CSF Q2W Arm III: Concurrent AC followed by paclitaxel Q3W Arm IV: Concurrent AC + G-CSF followed by paclitaxel + G-CSF Q2W Patients receive tamoxifen and RT post-chemo.	Protocol Description (PDQ)	1,407 cases with usable blocks	326 cases with usable slides	TMA in progress; ~1,429 cases	Paraffin block of primary tumor	2,005 patients	CALGB, ECOG, NCCTG, SWOG
CALGB-9343	Phase III Randomized Study of Adjuvant Tamoxifen with vs without Radiotherapy Following Lumpectomy for Carcinoma of the Breast No Greater Than 2 cm with Clinically Negative Axillary Nodes in Women Age 70 and Over	Arm I: Tamoxifen Arm II: Tamoxifen + Radiotherapy	Protocol Description (PDQ)	446 cases with usable blocks	157 cases with usable slides		Paraffin block of primary tumor	647 patients	CALGB, ECOG
CALGB-9344 (INT-0148)	Phase III Randomized Study of Adjuvant CA (Cyclophosphamide/ Doxorubicin) Comparing Standard- vs Intermediate- vs High-Dose Doxorubicin, with vs without Subsequent Paclitaxel, in Women with Node-Positive Breast Cancer	Arm I: Standard-dose doxorubicin not followed by paclitaxel Arm II: Medium-dose doxorubicin not followed by paclitaxel Arm III: High-dose doxorubicin not followed by paclitaxel Arm IV: Standard-dose doxorubicin followed by paclitaxel Arm V: Medium-dose doxorubicin followed by paclitaxel Arm VI: High-dose doxorubicin followed by paclitaxel	Protocol Description (PDQ)	2,449 cases with usable blocks	700 cases with usable slides	TMA completed, ~2,500 cases	Paraffin block of primary tumor	3,170 patients	CALGB, ECOG, NCCTG, SWOG
E1199	Phase III Randomized Study of Doxorubicin and Cyclophosphamide Followed By Paclitaxel or Docetaxel in Women With Node-Positive or High-Risk Node-Negative Stage II or IIIA Breast Cancer	Arm I: AC followed by paclitaxel 3 hrs Q3W X4 Arm II: AC followed by paclitaxel 1 hr Q1W X12 Arm III: AC followed by docetaxel 1 hr Q3W X4 Arm IV: AC followed by docetaxel 1 hr Q1W X12	Protocol Description (PDQ)	3,071 cases with usable blocks	1,484 cases with usable slides	TMA in progress (2,266 cases + 2,793 planned)	Paraffin block of primary tumor or unstained slides	5,052 patients	CALGB, ECOG, NCCTG
E2100	Phase III Randomized Study of Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer	Arm I: Paclitaxel followed by bevacizumab Arm II: Paclitaxel	Protocol Description (PDQ)	290 cases with usable blocks (Arm A: 148; Arm B: 142) (Recently-closed trial. Specimens still forthcoming from sites.)	282 cases with usable slides (Arm A: 139; Arm B: 143) (also includes some cases with blocks) (Recently-closed trial. Specimens still forthcoming from site.)	TMA planned; 724 cases	Paraffin block of primary tumor or unstained slides; if primary unavailable, block of metastatic tumor; serial serum and urine	722 patients	ECOG
E2190 (INT-0121)	Phase III Randomized Study of Adjuvant CAF (Cyclophosphamide/ Doxorubicin/Fluorouracil) vs Adjuvant CAF Followed by Intensification with High-Dose Cyclophosphamide/Thiotepa plus Autologous Stem Cell Rescue in Women with Stage II/III Breast Cancer At High Risk of Recurrence	Arm I: CAF Arm II: CAF followed by cyclophos./thiotepa + BM or PBSC rescue	Protocol Description (PDQ)	237 cases with usable blocks	28 cases with usable slides	235 cases on completed TMA + 300 cases planned	Strongly recommended: Paraffin block of primary tumor and, if possible, block of uninvolved ipsilateral axillary LN	540 patients	Primarily ECOG
E2197	Phase III Randomized Study of Doxorubicin/Docetaxel versus Doxorubicin/ Cyclophosphamide as Adjuvant Treatment for Node Positive or High Risk Node Negative Breast Cancer	Arm I: Doxorubicin + Docetaxel Arm II: Doxorubicin + Cyclophosphamide	Protocol Description (PDQ)	1,987 cases with usable blocks	443 cases with usable slides	1,534 on completed TMA + 1,424 planned	Paraffin block of primary tumor	2,952 patients	Primarily ECOG
E3193 (INT-0142)	Phase III Randomized Study of Adjuvant Tamoxifen with vs without Ovarian Ablation in Premenopausal Women with Axillary Node-Negative Receptor-Positive Breast Cancer 3 cm or Less in Diameter	Arm I: Tamoxifen Arm II: Tamoxifen + Ovarian albation	Protocol Description (PDQ)	223 cases with usable blocks	29 cases with usable slides		Paraffin block of primary tumor	345 patients	CALGB, ECOG, NCCTG, SWOG
E5194	Screening Study Following Local Excision in Selected Patients with Ductal Carcinoma in Situ (DCIS) of the Breast	(screening following local excision)	Protocol Description (PDQ)	341 cases with usable blocks	137 cases with usable slides	TMA planned; 712 cases	Paraffin block of primary tumor	711 patients	ECOG, NCCTG
E-EB193 (INT-0151)	Phase III Randomized Study of Adjuvant Tamoxifen/Fenretinide vs Tamoxifen/Placebo in Postmenopausal Women with Receptor-Positive Breast Cancer	Arm I: Tamoxifen/fenretinide Arm II: Tamoxifen/placebo	Protocol Description (PDQ)	376 cases with usable blocks	46 cases with usable slides	TMA planned; 426 cases	Paraffin block of primary tumor	426 patients	CALGB, ECOG, NCCTG, SWOG
EST-1180 (INT-0011)	Phase III Adjuvant Chemotherapy with CMFP (CTX/MTX/5-FU/PRED) and Evaluation of Biological Parameters in Node-Negative Operable Female Breast Cancer	Arm I: CMFP (Cyclophosphamide, Methotrexate, 5-Fluorouracil, Prednisone) Arm II: Observation	Protocol Description (PDQ)	656 cases with usable blocks	997 cases w/ usable slides at ECOG 895 cases w/usable slides at SWOG ~200 cases w/control slides	TMA planned; 1,223 cases	Paraffin blocks on every section of primary tumor or unstained slides	1,224 patients	ECOG (blocks and slides) SWOG (slides)
N9831	Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel with or without Trastuzumab as Adjuvant Treatment for Women with HER-2 Over-Expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer	Arm I: AC, followed by paclitaxel Arm II: AC, followed by paclitaxel, followed by trastuzumab Arm III: AC, followed by paclitaxel, followed by paclitaxel and trastuzumab, followed by trastuzumab All receptor+ pts receive tamoxifen or A.I.; selected pts may undergo RT	Protocol Description (PDQ)	(being determined - total of 3,505 patients accrued)	(being determined - total of 3,505 patients accrued)	TMA in progress; 400 cases	Tumor (primary) and serum submission at time of first recurrence; if not tumor, then 15 four-micron unstained slides; Baseline blood and (for select patients) serial blood	3,505 patients	primarily NCCTG
NCIC-JMA17	Phase III Randomized Study of Letrozole Versus Placebo in Postmenopausal Women With Primary Breast Cancer Who Have Completed at Least Five Years of Adjuvant Tamoxifen	Arm I: Letrozole (following > 5 yrs tamoxifen) Arm II: Placebo (following > 5 yrs tamoxifen)	Protocol Description (PDQ)	600 cases with blocks at Group banks (Specimens still forthcoming from sites.)	(Specimens still forthcoming from sites.)	TMA planned; 900 cases	Block of primary tumor or unstained slides	~5,100 patients	CALGB, ECOG, NCCTG, NCIC CTG, SWOG
NCIC-MA.21	A Phase III Adjuvant Trial of Sequenced EC + Filgrastim + Epoetin Alfa Followed by Paclitaxel Versus Sequenced AC Followed by Paclitaxel Versus CEF as Therapy for Premenopausal Women and Early Postmenopausal Women Who have had Potentially Curative Surgery for Node Positive or High Risk Node Negative Breast Cancer	Arm I: CEF Q4W x 6 Arm II: EC + G-CSF Q2W x 6 + epoetin alpha weekly followed by paclitaxel + G-CSF Q3W x 4 + epoetin alpha weekly Arm III: AC Q3W x 4 followed by paclitaxel Q3W x 4 ER+/PR+ pts receive tamoxifen or anastrozole for 5 years after chemo completion	Protocol Description (PDQ)	TBA	TBA	TMA planned; 2,000 cases	Paraffin block of tumor and, where possible, normal tissue; baseline serum	2,104	Primarily NCIC CTG
S9623	Phase III Randomized Study of Intensive Sequential Doxorubicin, Paclitaxel, and Cyclophosphamide Versus Doxorubicin and Cyclophosphamide Followed By STAMP I or STAMP V Combination Chemotherapy With Autologous Stem Cell Rescue in Women With Primary Breast Cancer and At Least 4 Involved Axillary Lymph Nodes	Arm I: Doxorubicin, paclitaxel, cyclophosphamide, + G-CSF Arm II: Doxorubicin, cyclophosphamide + harvest of autologous bone marrow or PBSC; followed by STAMP I (cyclophosphamide, cisplatin, carmustine) or STAMP V(cyclophosphamide, carboplatin, thiotepa), followed by transplantation tamoxifen daily and locoregional radiotherapy	Protocol Description (PDQ)	388 cases with usable blocks	119 cases with usable slides		Block of primary tumor, peripheral blood progenitor cells (PBPC)	602 patients	CALGB, ECOG, NCCTG, SWOG
S9927	Phase III Randomized Study of Radiotherapy After Mastectomy and Adjuvant Chemotherapy and/or Hormonal Therapy in Women With Stage II Breast Cancer With One to Three Positive Nodes	Arm I: Radiotherapy Arm II: Observation	Protocol Description (PDQ)	32 cases with usable blocks	42 cases with usable slides		Block of primary tumor or unstained slides	98 patients	Primarily SWOG
SWOG-8814 (INT-0100) (including companions SWOG-9445 & 8854)	Phase III Randomized Comparison of Adjuvant Therapy with Tamoxifen vs CAF plus Concurrent or Delayed Tamoxifen in Postmenopausal Women with Node- and Receptor-Positive Breast Cancer	Arm I: Tamoxifen Arm II: CAF followed by tamoxifen Arm III: CAF plus concurrent tamoxifen Regimen A: Radiotherapy (lumpectomy) Regimen B: Radiotherapy (selected mastectomy pts)	Protocol Description (PDQ)	431 cases with usable blocks (420 tumor, 11 metastatic LN)	661 cases with usable slides of tumor 14 cases w/met LN		Block of highest-grade primary tumor, block of highest grade regional node metastasis (for companion study)	1,558 patients	Primarily SWOG
SWOG-8897 (INT-0102)	Phase III Randomized Comparison of Adjuvant Chemotherapy with CMF vs CAF with vs without Long-Term Endocrine Therapy with Tamoxifen in High-Risk Node-Negative Breast Cancer Patients and a Natural History Follow-Up Study in Low-Risk Node-Negative Patients	Arm 0: Observation arm/ natural history (small tumor size, ER+, low S phase) Arm I: CMF Arm II: CAF Arm III: CMF followed by Tamoxifen Arm IV: CAF followed by TMX. Regimen A: Radiotherapy	Protocol Description (PDQ)	0	1,702 cases with usable slides		Block of primary tumor; block of normal axillary lymph node	4,406 patients	SWOG (slides)
SWOG-9313 (INT-0137)	Phase III Randomized Study of Adjuvant Chemotherapy with High-Dose Doxorubicin/ Cyclophosphamide (AC) vs Doxorubicin Followed by Cyclophosphamide (A-C) in Women with High-Risk Breast Cancer and 0-3 Positive Nodes	Arm I: doxorubicin followed immediately by cyclophosphamide every 3 weeks for 6 courses + G-CSF followed by tamoxifen Arm II: doxorubicin every 3 weeks for 4 courses, followed by cyclophosphamide every 2 weeks for 3 courses + G-CSF followed by tamoxifen	Protocol Description (PDQ)	~2,305 cases with usable blocks	248 cases with usable slides	2,123 cases on completed TMA	Block of primary tumor	3,176 patients	CALGB, ECOG, NCCTG, SWOG

Contacts for TBCI specimen banks

TBCI Group banks:

ACOSOG breast cancer specimen bank

Mark Watson, M.D., Ph.D.
Washington University School of Medicine, St. Louis, MO
Phone: 314-454-7919
Email: watsonm@wustl.edu
ACOSOG Web site: www.acosog.org

CALGB breast cancer specimen bank

Scott Jewell, Ph.D.
Laura Monovich
Ohio State University, Columbus, OH
Phone: 614-293-7073
Email: Scott.Jewell@osumc.edu, Laura.Monovich@osumc.edu
CALGB Web site: http://www.calgb.org

ECOG breast cancer specimen bank

Michael Pins, M.D.
Adekunle Raji
Northwestern University, Chicago, IL
Phone: 312-908-9595
Email: ecogpcorl@northwestern.edu, m-pins@northwestern.edu, a-raji@northwestern.edu
ECOG Web site: http://ecog.dfci.harvard.edu

NCCTG breast cancer specimen bank

Wilma Lingle, Ph.D.
Mayo Clinic, Rochester, MN
Phone: 507-538-1287
Email: lingle.wilma@mayo.edu
NCCTG Web site: http://ncctg.mayo.edu

NCIC CTG breast cancer specimen bank

Lois Shepherd, M.D.
Shakeel Virk
Queen's University, Kingston, Ontario, Canada
Phone: 613-533-6430 ext. 77714
Email: lshepherd@ctg.queensu.ca, virk@cliff.path.queensu.ca
NCIC CTG Web site: http://www.ctg.queensu.ca

SWOG breast cancer specimen bank

Wilbur Franklin, M.D.
University of Colorado, Denver, Colorado
Phone: 303-724-3080
Email address: wilbur.franklin@uchsc.edu

Jerry Haney (technical contact in Colorado)
University of Colorado, Fitzsimons Campus, Aurora, Colorado
Phone: 303-723-3081
Email address: jerry.haney@uchsc.edu

SWOG Web site: www.swog.org

Proposals approved by the Committee

Study No.	Approval status	Correlative study title	Markers/ methodology approved	Clinical trial from which specimens are used	Correlative study P.I.	Publications/ abstracts
7613	Active study	"Identifying Genomic Predictors of Recurrence after Adjuvant Chemotherapy"	Identification of individual genes as well as multi-gene RNA expression profile to predict benefit from taxane/ relapse after non-taxane-containing chemotherapy	E2197 Clinical trial descriptions	Joseph Sparano, M.D.	Abstract 526 - 2007 ASCO Annual Meeting
CALGB-159905	Active study	"Correlative Studies of ERB B-2/HER-2/NEU and P53 in CALGB Protocol 9344/INT Protocol 0148"	ERB B-2/ HER-2, TOPO2, P53	CALGB-9344 (INT-0148) Clinical trial descriptions	Daniel Hayes, M.D.	Manuscript on HER2 in press.
E2100ICSC	Approved study	"Molecular profiling of E2100 FFPE samples using a custom 512 gene set on the DASL platform"	512-gene set	E2100 Clinical trial descriptions	Brian Leyland-Jones, M.D., Ph.D.
E2100T1-ICSC	Active study	"Differential response of breast cancer patients on E2100 treated with bevacizumab as a function of genetic polymorphisms of VEGF and KDR"	Correlation of VEGF and KDR polymorphisms with outcome, efficacy, and gene expression.	E2100 Clinical trial descriptions	Bryan Schneider, M.D.
MA.17ICSC	Active study	"Quantitative Protein and Gene Expression Biomarkers of Tamoxifen and Letrozole Recurrence in the NCIC CTG MA.17 Cohort"	Evaluation of prognostic and predictive utilities of two gene expression signatures; evaluation of quantitative immunofluorescence (various markers); novel gene expression profile development	NCIC-JMA17 Clinical trial descriptions	Paul Goss, M.D., Ph.D., and Dennis Sgroi, M.D.
NCCTG N9831-ICSC	Approved Study	"Analyses of c-Myc (MYC) and topoisomerase II alpha (TOP2A) copy number aberrations; and MYC, insulin-like growth factor receptor-1 (IGF-1R) and PTEN protein expressions in N9831 primary breast tumors."	MYC IGF-1R PTEN TOP2A	N9831 Clinical trial descriptions	Edith Perez, M.D.
S0221A-ICSC	Active study	"Impact of antioxidant supplements and polymorphisms in ROS-related genes on toxicity and breast cancer recurrence in patients enrolled on S0221"	Antioxidant supplement use, polymorphisms in genes that produce and protect from reactive oxygen species (ROS) - MPO, eNOS, MnSOD, GPX1, CAT, GSTP1, GSTAI, GSTM1, GSTT1, NQO1, NRF2	S0221 Clinical trial descriptions	Christine B. Ambrosone, Ph.D.
S8814A-ICSC	Active study	"Molecular Predictors of Outcome on CAF plus Tamoxifen versus Tamoxifen Alone in Postmenopausal Women with Node-Positive, Receptor-Positive Breast Cancer"	Evaluation of prognostic and predictive utilities of a gene expression signature in node-positive, receptor-positive breast cancer	SWOG-8814 (INT-0100) Clinical trial descriptions	Kathy Albain, M.D.	Albain et al SABCS 2004
S9313A	Closed study	"The Evaluation of Cyclin E and p27 Expression in Breast Cancers of High Risk Women Treated with Adriamycin and Cyclophosphamide in SWOG/Intergroup Protocol #9313"	Cyclin E, p27	SWOG-9313 (INT-0137) Clinical trial descriptions	Peggy Porter, M.D.	Porter P.L., et al. J Natl Cancer Inst. 98:1723-31, 2006
S9313A-ICSC	Active study	"Prediction of Therapeutic Response using AQUA Quantitative Protein Expression analysis of ER, PgR, and HER2 of Breast Cancer Tissue Microarrays from SWOG Protocol 9313"	Correlation of ER, PR, HER2, p53 via AQUA with recurrence and mortality in patients who have received uniform AC treatment	S9313 (INT-0137)	David Rimm, M.D., Ph.D.
SWOG-8897-ICSC	Active study	"Pharmacogenetics in relation to breast cancer outcomes in SWOG 8897"	Polymorphisms resulting in greater activation of cyclophosphamide, and polymorphisms resulting in less production of quinone-related oxidative damage of adriamycin.	SWOG-8897 (INT-0102) Clinical trial descriptions	Christine B. Ambrosone, Ph.D.	Ambrosone C.B., et al. SABCS, 2006
TBCI-C1	In development	"RNA banking procedures for TBCI correlative science studies with FFPE tissue"	Extraction, amplification, and preservation of RNA from FFPE tissue	CALGB-9344 (INT-0148) SWOG-8814 (INT-0100) Clinical trial descriptions	Matthew Ellis, M.B., Ph.D.
TBCI-S1	Active study	"Correlative Science Studies for SWOG Protocol S9313" (HER-2 and TOPO2 as indicators of need for additional therapy after AC, or A'C vs. AC)"	HER-2, topoisomerase 2	SWOG-9313 (INT-0137) Clinical trial descriptions	Raymond Tubbs, D.O.

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TBCI Breast Cancer Specimens Available for Research Correlative Sciences Committee

Introduction