Below please find instructions to investigators seeking to request specimens from the North American Breast Cancer Group (NABCG) Correlative Sciences Committee (CSC) for use in correlative scientific studies.
The North American Breast Cancer Group (NABCG) is a network of the National Cancer Institute (NCI)-sponsored Cooperative Groups conducting research in breast cancer.
The NABCG Correlative Sciences Committee is charged with fostering and reviewing proposals from investigators wishing to obtain specimens collected from NABCG clinical trials for use in correlative studies addressing questions of prognosis and prediction in patients with breast cancer. NABCG trials are usually phase 3 trials, but may also include larger phase 2 trials.
Chaired by Dr. Daniel F. Hayes of the University of Michigan, the NABCG Correlative Sciences Committee consists of representatives from each NABCG-member Cooperative Group (ACOSOG, ACRIN, CALGB, ECOG, NCCTG, NCIC CTG, NSABP, RTOG, and SWOG), as well as representatives from the NCI.
NABCG 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 NABCG’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 (TMA’s) have been constructed using these tissues.
Since most NABCG 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 specimen resources that are more appropriate to these types of studies, such as the Cooperative Human Tissue Network (CHTN), and the NCI CDP breast tissue microarrays.
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 NABCG has banked. 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 NABCG 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 NABCG specimens by investigators with worthy study proposals.
The numbers contained in the Inventory of Specimens Collected from Group Breast Cancer Studies are approximate as of 2011 or late 2010. For the specific number of usable specimens that are currently available, please contact the appropriate Group bank(s) as noted in the inventory.
Please note: Specimen numbers will change for open and closed trials, where collection is still underway and a portion is reserved for embedded lab objectives.
Please note: Specimen numbers will change for completed and published therapeutic trials, where specimens are reserved/distributed for approved projects.
Please see the listing of specimens collected from breast cancer studies of the NABCG Groups. This listing indicates 1) which Cooperative Group you should contact to inquire about specimen availability and 2) which process you need to go through to apply for those specimens — i.e., the NABCG Correlative Sciences Committee or the individual Cooperative Group. The inventory also indicates where specimens are banked.
Investigators must submit their proposals using the NABCG 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 email@example.com. The Committee accepts only electronic submissions.
Inquiries regarding funding and new ideas for studies, including appropriate specimen collections, should be directed to:
Daniel Hayes, M.D.
Chair, NABCG Correlative Sciences Committee
Proposals should be submitted to:
Protocol & Information Office
Cancer Therapy Evaluation Program
National Cancer Institute
Only electronic submissions are accepted.
Applications are accepted on a rolling basis. Reviews are monthly. Investigators should expect notification of the NABCG Correlative Sciences Committee’s decision on a proposal within 6-8 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.
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 Chair of the NABCG Correlative Sciences Committee can guide investigators to the appropriate individuals within the Cooperative Group that led the trial. Review and endorsement of the proposal by this lead Cooperative Group is recommended.
However, investigators can submit a correlative science proposal to the NABCG Correlative Sciences Committee independently.
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 firstname.lastname@example.org or phone: 734-615-6725.
Application to potential funding sources other than the NABCG Correlative Sciences Committee (for example, grant applications) should be submitted only after approval from the NABCG Correlative Sciences Committee has been obtained. Although the NABCG Correlative Sciences Committee encourages grant proposals requesting funding to perform studies using NABCG material, investigators are discouraged from submitting for potential funding until and if the proposal is approved by the NABCG 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, the NABCG Correlative Sciences Committee 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 the NABCG 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 the Chair of the NABCG Correlative Sciences Committee 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.
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 NABCG Correlative Sciences Committee. In this way, all recommendations from the internal review can be incorporated into the proposal by the time the NABCG Correlative Sciences 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 NABCG Correlative Sciences Committee.
In other words, the NABCG Correlative Sciences Committee should see the "best and final" version of the proposal.
Scientific approval by the NABCG Correlative Sciences Committee is not required for the lead Group to construct a tissue-microarray (TMA) from NABCG 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 NABCG TMA’s. Recommended assays for standard ER, PgR, HER2 assessment include the following:
IHC: SP1 or 1D5
IHC: Pg6/636 Dako
IHC: Herceptest or Cb11
FISH: Pathvysion® or Dako pharmDx™
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.
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 NABCG representation as required for NABCG clinical trials.
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 NABCG Correlative Sciences Committee, if they so choose.
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 such 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 NABCG’s clinical trials.
For example, an application requesting use of specimens from a NABCG 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 NABCG clinical trial specimens, including the carefully collected patient outcome and other clinical data with which they are associated, the NABCG Correlative Sciences 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.
The following types of studies are subject to NABCG Correlative Sciences Committee review:
Stand-alone correlative studies that are not embedded in the protocol for an Intergroup (e.g., NABCG) trial at the time of the protocol’s initial submission to CTEP.
NOTE: To determine which trials’ specimens are subject to NABCG CSC review, please consult the “Where to apply for specimens” column the NABCG specimen inventory.
Additional embedded correlative studies that are proposed to be embedded in a clinical trial protocol as part of a protocol amendment — i.e., after CTEP has approved the protocol. The NABCG Correlative Sciences Committee should review these additional embedded studies before CTEP review.
The following are subject to CTEP review:
Correlative studies embedded into a clinical trial protocol submitted to CTEP, and any amendments to those studies.
Additional embedded correlative studies that are proposed to be embedded in a clinical trial protocol as part of a protocol amendment. These are also subject to NABCG CSC review if the trial is an Intergroup (e.g., NABCG) trial.
NOTE: Proposals for stand-alone studies using specimens from a trial conducted by a single Group, as opposed to an Intergroup (e.g., NABCG) must also be submitted to CTEP, in addition to the Group. The NABCG specimen inventory indicates which trials of the NABCG-member Groups are single-Group trials. (In these cases, please check the instructions on the Group’s website to determine if the Group will submit your proposal to CTEP for you.).
Note: If you are applying for specimens from an individual Cooperative Group, as opposed to the NABCG Correlative Sciences Committee (the NABCG specimen inventory indicates which studies go through the Group and which go through the NABCG CSC), your proposal must be submitted to CTEP once your proposal has been approved by the Group. Please check the instructions on the Group’s website to determine if the Group will submit your proposal to CTEP for you. Your proposal will need CTEP approval if it uses specimens from at least 100 patients. If it uses specimens from fewer than 100 patients, your proposal still must be submitted to CTEP so that NCI can register the study in its database.
If you are applying for specimens available via the NABCG Correlative Sciences Committee, your proposal will not need an additional CTEP review. (The NABCG specimen inventory indicates which studies go through the Group and which go through the NABCG CSC.)
Once a proposal is reviewed by the NABCG Correlative Sciences 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 re-review by the NABCG Correlative Sciences Committee or if only an abbreviated re-review is required.
Once the investigator receives word that his/her proposal has been approved by the NABCG Correlative Sciences Committee, notification that the correlative study has received scientific approval from the NABCG 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.
An approved proposal will also be sent to the CTEP Regulatory Affairs Branch (RAB) so that they can check to see if there is a CRADA in place and, if so, to give the pharmaceutical company 30 days to respond with any comments.
Approval by the NABCG Correlative Sciences Committee pertains only to scientific review. Therefore, following approval of a correlative study by the NABCG 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, obtaining funding, and so forth.
Principal Investigators of studies approved by the NABCG 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 NABCG 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.
|Study number||Title of correlative study||Principal Investigator|
|Identifying Genomic Predictors of Recurrence after Adjuvant Chemotherapy (E2197 specimens)
|Dr. Joseph Sparano|
|CALGB-159905||Correlative Studies of erbB -2/HER-2/NEU and P53 in CALGB Protocol 9344/INT Protocol 0148: "Doxorubicin Dose Escalation, with or without Taxol, as Part of the CA Adjuvant Chemotherapy Regimen for Node Positive Breast Cancer: A Phase III Intergroup Study (CALGB-9344 specimens)||Dr. Matthew Ellis|
|CALGB-159905B-ICSC||Breast Cancer Subtype (as Defined by HER2, Er, Ki67) as Predictive Factors for Sensitivity to Paclitaxel, and the Triple-Negative Subtype (Basal Versus Non-Basal) as Prognostic Factors in Intergroup Trial CALGB 9344
|Dr. Matthew Ellis|
|CALGB-159905C-ICSC||Intrinsic Breast Cancer Subtypes and Benefit of Paclitaxel in CALGB 9344 and Dose Dense Therapy in CALGB 9741||Dr. Matthew Ellis|
|CALGB-9343A-CALGB-ICSC||PIK3CA Mutation Status as a Biomarker in Elderly Women with Breast Cancer||Dr. Mary Ellen Moynahan|
(part of CALGB-159905)
|ER/HER2/Ki67 Breast Cancer Subtypes as Predictive Factors for Response to Adjuvant Dose-Dense Therapy, and Basal Subtypes of Triple-Negative Breast Cancer as Prognostic Factors in Intergroup Trial C9741||Dr. Matthew Ellis|
|E2100ICSC||Molecular Profiling of E2100 FFPE Samples Using a Custom 512 Gene set on the DASL Platform||Dr. Brian Leyland-Jones|
|E2100T1-ICSC||Differential Response of Breast Cancer Patients on E2100 Treated with Bevacizumab as a Function of Genetic Polymorphisms of VEGF and KDR
|Dr. Bryan Schneider|
|ECOG E2100D-ECOG-ICSC||VEGF Gene Amplification/Deletion and Haplotype as Biomarkers for Bevacizumab in Breast Cancer||Dr. Bryan Schneider|
|ECOG E5194A-ECOG-ICSC||Correlative Science Study for ECOG E5194||Dr. Lawrence Solin|
|ECOG-E1199C-ECOG-ICSC||Genetic Predictors of Taxane Induced Peripheral Neuropathy in E1199||Dr. Bryan Schneider|
|ECOG-E2197B-ICSC||Molecular Profiling of E2197 FFPE Samples Using a Custom 512 Breast Cancer Gene Set on the DASL Platform: Towards the Development of Predictive Gene Sets for Risk of Recurrence in Patients with Operable Breast Cancer Treated with Adjuvant Therapy||Dr. Brian Leyland-Jones|
|ECOG-E5103A-ECOG-ICSC||Biomarker Prediction of Chemotherapy-Related Amenorrhea in Premenopausal Women with Breast Cancer Participating in E5103||Dr. Kathryn Ruddy|
|MA.17ICSC||Quantitative Protein and Gene Expression Biomarkers of Tamoxifen and Letrozole Recurrence in the NCIC MA.17 Cohort||Dr. Paul Goss|
|NCCTG N9831-ICSC||Analyses of c-Myc (MYC) and Topoisomerase II Alpha (TOP2A) Copy Number Aberrations; MYC, Insulin-like Growth Factor Receptor-1 (IGF-1R) and PTEN Protein Expressions; and Phosphatidylinositol 3 Kinase (PIK3) Gene Mutations in N9831 Primary Breast Tumors
|Dr. Edith Perez|
|NCCTG-N9831(B)-NCCTG-ICSC||Gene Expression Profiling of N9831FFPE Breast Tumors Using a 24,000 (24K) Gene Panel on the cDNA-Mediated Annealing, Selection, Extension and Ligation (DASL) Platform||Dr. Edith Perez|
|NCCTG-N9831(C)-NCCTG-ICSC||Round-Robin Clinico-Pathological Review of HER2 Testing in the Context of Adjuvant Therapy for Breast Cancer (N9831, BCIRG 006, and BCIRG 005)
|Dr. Edith Perez|
|NCCTG N9831D-NCCTG-ICSC||Adjuvant chemotherapy combined with trastuzumab in the randomized phase III trial N9831 actively immunizes patients against tumor Antigens||Dr. Keith Knutson and Dr. Edith Perez|
|NCCTG-N9831E-NCCTG-ICSC||Automated Quantitated Analyses (AQUA) of Epidermal Growth Factor Receptor (EGFR), p95/HER2, HER3, HER4, PTEN, and PI3Kp110alpha in N9831 Primary Breast Tumors using Tissue Microarrays||Dr. Edith Perez|
|NCCTG N9831F-NCCTG-ICSC||N9831 validation study of Quantitative Single Gene Assessment of HER2 mRNA by qRT-PCR and Development and Testing of New HER2 Multi-Gene Signature||Dr. Edith Perez|
(NCI number: NCIC-MA.27(B)-MAYO-ICSC)
|A Genome-Wide Association Study in Patients Experiencing Musculoskeletal Adverse Events on NCIC CTG Trial MA.27 Evaluating Aromatase Inhibitors as Adjuvant Therapy in Early Breast Cancer. A Collaboration Between the NIH Pharmacogenetics Research Network and the RIKEN Yokohama Institute Center for Genomic Medicine
|Dr. James Ingle|
|NCIC-MA.27C-MGH-ICSC||A Genome-Wide Association Study in Patients Experiencing Bone Fractures While Receiving Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27. A collaboration between Massachusetts General Hospital Cancer Center, the Mayo Clinic NIH Pharmacogenetics Research Network Center, the RIKEN Yokohama Institute Center for Genomic Medicine and NCIC CTG Canada.||Dr. Paul Goss|
|NCIC-MA.27E-MAYO-ICSC||A Genome-Wide Association Study in Patients Experiencing Breast Events While Receiving Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27||Dr. James Ingle|
|S0221A-ICSC||Impact of Antioxidant Supplements and Polymorphisms in ROS-related Genes on Toxicity and Breast Cancer Recurrence in Patients Enrolled on S0221
|Dr. Christine Ambrosone|
|S8814A-ICSC||Molecular Predictors of Outcome on CAF plus Tamoxifen versus Tamoxifen Alone in Postmenopausal Women with Node-Positive, Receptor-Positive Breast Cancer||Dr. Kathy Albain|
|S9313A||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
|Dr. Peggy Porter|
|S9313A-ICSC||Prediction of Therapeutic Response using AQUA Quantitative Protein Expression analysis of ER, PgR, and HER2 of Breast Cancer Tissue Microarrays from SWOG Protocol 9313
|Dr. David Rimm|
|SWOG 8897B-SWOG-ICSC||Gene Variants in Drug Cytotoxicity Pathways and Breast Cancer Survival and Toxicity in SWOG 8897
|Dr. Christine Ambrosone|
|SWOG-8897-ICSC||Pharmacogenetics in Relation to Breast Cancer Outcomes in SWOG 8897
|Dr. Christine Ambrosone|
|SWOG-S9313B-ICSC||Evaluation of the Expression of the Cancer Stem Cell Marker ALDH1 as a Predictor of Adjuvant Chemotherapy Response in Breast Cancers of High Risk Women in SWOG-9313||Dr. Daniel Hayes|
|Correlative Science Studies for SWOG Protocol S9313: Phase III Comparison of Adjuvant Chemotherapy with High-Dose Cyclophosphamide plus Doxorubicin (AC) versus Sequential Doxorubicin followed by Cyclophosphamide (A'C) in High Risk Breast Cancer Patients with 0-3 Positive Nodes||Dr. Daniel Hayes|