BREAST CANCER AND THE ENVIRONMENT RESEARCH CENTERS

RELEASE DATE:  November 11, 2002 (see addenda NOT-ES-03-004, NOT-ES-03-006)

RFA:  ES-03-001

Update: The following update relating to this announcement has been issued:

November 18, 2009  - See Notice NOT-ES-10-001 Clarification of Eligibility as Primary Applicant.
October 23, 2009 - This RFA has been reissued as (RFA-ES-09-008).

National Institute of Environmental Health Sciences (NIEHS) 
 (http://www.niehs.nih.gov)
National Cancer Institute (NCI)
 (http://www.nci.nih.gov)

Letter of Intent Receipt Date:  December 31, 2002

Application Receipt Date:  February 11, 2003

THIS RFA CONTAINS THE FOLLOWING INFORMATION:

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE

The National Institute of Environmental Health Sciences (NIEHS) and the 
National Cancer Institute (NCI) invite applications to create a network of 
research centers in which multidisciplinary teams of scientists, clinicians, 
and breast cancer advocates work collaboratively on a unique set of scientific 
questions that focus on how chemical, physical, biological, and social factors 
in the environment work together with genetic factors to cause breast cancer. 
Answering these questions will allow the translation of such findings into 
information that can be applied to increase awareness of the causes of breast 
cancer.  This program will support a network of cooperative agreements (U01) 
comprised of research teams, which will work within and across centers on 
targeted biological and epidemiologic research projects.  These projects will 
be designed to fill specific gaps related to how environmental exposures 
impact the development of the mammary gland at the cellular, molecular, organ, 
and population level throughout a woman=s lifetime to influence future breast 
cancer risk.  The research conducted will take a unique developmental approach 
to integrate time, susceptibility and exposure in order to more fully 
appreciate the changes that occur in the mammary gland early in life that may 
predispose the breast to cancer.  These projects will help to define specific 
periods of susceptibility of the breast when environmental stressors may 
change the molecular architecture of the gland, conferring increased risk of 
future cancer.  The purpose of implementing a network of cooperative breast 
cancer centers is twofold.  The first goal is to integrate scientific 
information on histologic, pathologic, cellular, and sub-cellular changes that 
occur in normal mammary gland tissue across the lifespan and compare this to 
exposure-induced changes.  Discovering changes in gene and protein expression 
due to agents to which young girls and women may be exposed during their 
lifetime will be a primary goal.  Experiments will be conducted cooperatively, 
using animal models that characterize pathways related to breast and endocrine 
system development during early life, puberty, pregnancy, and other time 
points, which may be affected by exposures to environmental stressors 
occurring at different windows of vulnerability.  When clinical specimens are 
available from women at risk, they will be compared to animal models.  Data 
from these experiments will be made available to the scientific community in 
order to stimulate further investigations of mechanisms of interest.  A second 
goal is to conduct a focused and coordinated epidemiologic study of 
determinants of puberty in girls.  Attention will be paid to understanding the 
shift towards earlier puberty among adolescent girls, the identification of 
environmental exposures in young girls, and the interplay between genetic 
polymorphisms and environmental exposures that may put them at risk of future 
breast cancer. The overall goal of this network of centers is to integrate the 
basic biological, toxicologic, and epidemiologic data on the development and 
lifespan of the mammary gland in a way that public health messages can be 
designed to educate young girls and women who are at high risk of breast 
cancer on the role of specific environmental stressors in breast cancer 
development and how to reduce exposure to those agents.  This information will 
be useful in developing clinical and public health programs that target breast 
cancer prevention in young girls and women.  This research program complements 
other programs on breast cancer and mammary gland development being conducted 
at the National Institutes of Health.  The unique focus of this program 
extends that research by comparing the effects of environmental stressors, 
including environmental pollutants, nutritional and lifestyle factors, and 
other exposures on normal mammary gland development in order to more fully 
consider the multiple causes of breast cancer. 

RESEARCH OBJECTIVES

Background

Breast cancer is a complex disease, the causes of which have eluded scientists 
for many decades.  Improvements have been made in early disease detection, 
surgical and medical modalities for treatment and survival for women with 
breast cancer.  Although scientists and clinicians understand more today about 
the process of carcinogenesis and genetic susceptibility, effective prevention 
strategies targeting the causes of breast cancer remain out of reach due to 
the multiplex of factors involved in breast cancer causation.  Historically, 
research to understand the causes of breast cancer has focused primarily on 
the role of estrogen.  The dose of estrogen to the mammary gland varies over 
time during a woman=s life and may produce differential risks of cancer.  The 
need to focus on critical windows of vulnerability of the mammary gland, 
especially the period of time between the onset of menarche and first 
pregnancy, has been recommended by scientists as central to advancing our 
knowledge.  New technologies are being used to understand the molecular 
aspects of cell growth and proliferation during this and other critical 
windows and provide new opportunities to integrate molecular, cellular and 
organ system level data.  Recently, in a series of workshops and meetings 
conducted by NIEHS, scientists proposed a developmental approach to 
understanding the initiation of breast cancer, drawing attention to the gaps 
in our knowledge concerning normal development of the mammary gland, 
physiology of sexual maturation, and genetic regulation of these processes.  A 
major gap was the lack of data available on environmental factors that may 
perturb these systems.  There is a need to integrate data on the structure and 
dynamics of cellular and organ system functions from experimental and clinical 
models of breast development, in order to look at normal physiological 
pathways and alterations that may occur from environmental stressors.  This 
approach may allow scientists to think about the interplay between 
environmental, genetic, and physiologic causes of breast cancer in a new way.

During the past decade NIEHS has supported research that has focused on 
understanding the mechanisms of selected environment agents on breast cancer 
in individuals and in populations.  Research programs have focused on 
understanding the mechanisms of endocrine disrupting chemicals on the female 
hormonal and reproductive systems, timing of exposures to environmental 
toxicants and breast cancer risk, and genetic susceptibility to breast cancer. 
From recent epidemiologic studies it appears that exposures to DDT and 
polychlorinated biphenyls (PCBs) as measured in adulthood are not related to 
breast cancer risk in women living in countries where these chemicals are 
banned.  There are some studies suggesting increased risk in women where 
spraying with DDT continues today.  There is evidence that prenatal exposures 
to dioxin and soy have an effect on mammary gland development.  Work has begun 
to explore the perturbations in molecular mechanisms of mammary gland 
development in experiments using DDT, PCBs, and polyaromatic hydrocarbons 
(PAHs) as exposures.  The National Toxicology Program rodent bioassay suggests 
that there are about 40 chemicals that cause breast cancer.  Many are 
industrial exposures and are therefore difficult to study in women.  Recent 
evidence suggests other chemicals such as bisphenol-A, atrazine, certain 
heterocyclic amines and other polyaromatic hydrocarbons may affect mammary 
gland development by changing the pattern of branching in the breast affecting 
primarily the terminal end buds.  Scientists are also currently exploring how 
chemical exposures may change the hormonal milieu and how these changes can 
impact breast cancer risk.  Following on the need to understand what is 
happening to the mammary gland during critical windows of susceptibility, 
there is strong evidence that girls less than 14 years old at the time of the 
atomic bomb in Hiroshima have an increased risk of breast cancer.  It has been 
suggested that early cigarette smoking in adolescence may also increase risk. 
Recent work in Michigan has shown that girls whose mothers were exposed to 
polybrominated biphenyls (PBBs) during their pregnancy and after have an 
earlier onset of menarche.  Although evidence exists for selected chemicals, 
most of the 70,000 chemicals in commerce today remain untested and little data 
are available on human doses of exposure or cellular or physiologic effects of 
these exposures on the mammary gland and female reproductive system. 

During the past decade the NCI has also been actively supporting research on 
the role of environmental factors on the risk of breast cancer, particularly 
through epidemiological research and the development of tools such as 
geographic information systems.  Some of these studies have been jointly 
funded with the NIEHS.  NCI-supported research has led to the identification 
of multiple reproductive factors that are involved in the development of 
breast cancer.  However, there are still significant gaps in the knowledge of 
changes that occur in normal breast tissue throughout the lifespan and the 
need for more research on the impact of environmental stressors on breast 
tissue and pubertal development that may affect breast cancer risk. 

In addition to studying traditional environmental factors such as chemicals 
and physical agents, it is necessary to more completely examine the influence 
of anthropometric and nutritional factors on the mammary gland during 
development, puberty, pregnancy, lactation and menopause.  There have been 
temporal changes noted in body size, weight, and adiposity in young girls over 
recent decades that may contribute to earlier age at menarche, precocious 
puberty, and altered hormonal profiles.  These changes in physiological 
parameters may account for the rise in a woman=s risk of future breast cancer. 
Social environmental factors, such as poverty, family structure and stress may 
impact on nutritional choices, physical activity levels, body size and shape, 
and pubertal development and translate to breast cancer risk factors.  There 
are many gaps in our understanding of how the growth and development of the 
mammary gland and reproductive system in young girls may be influenced by 
environmental factors such as changing dietary habits, lifestyle choices, 
physical activity, and exposures to chemicals in products being used by young 
girls.  This limited evidence will provide a starting point in considering 
which environmental exposures to consider for more in depth study in both the 
biological and epidemiologic components of this program.  

Biological data on cellular and sub-cellular outcomes should be more fully 
integrated in a way that can facilitate analyses of the interplay between all 
factors that may cause breast cancer.  Such an effort can be useful to examine 
and differentiate the multi-level interactions that impact the mammary gland 
and reproductive system as they change over a woman=s lifetime.  This 
information will enhance our appreciation of the biological basis of sexual 
maturation and allow scientists to test new hypotheses in mechanistic, 
clinical and epidemiologic studies.  A coordinated multi-site study of the 
environmental and genetic determinants of puberty will translate the basic 
information on the influence of many factors on the developing breast and 
reproductive system in young girls to the population level.  These two 
scientific efforts will provide valuable information to the general public on 
how the total environment of young girls and women impacts the health of the 
breast.  Components of these projects will contribute to our understanding of 
the heterogeneity of the disease, susceptibility to breast cancer among 
different groups of women, the development, validation and use of markers of 
physiologic changes in the breast, and the mechanisms of action of chemicals 
and other exposures in causing breast cancer.

Objectives

Each Breast Cancer and the Environment Research Center will be constructed in 
a way to contribute to the collective effort to provide new information on the 
normal growth and development of the breast and reproductive systems, provide 
data at the sub-cellular, cellular, and organ system level in animal models 
and human populations, evaluating the impact of environmental stressors on the 
mammary gland, and explore issues related to susceptibility in developing 
breast cancer.  The following five scientific priority areas have been 
developed after a series of workshops and meetings held on this topic attended 
by scientists, representatives from breast cancer advocacy groups and health 
care practitioners.  They are:   

o defining the molecular architecture of the developing and changing mammary 
gland over the lifespan,  

o timing of exposure during critical windows of vulnerability, 

o creation of new and improved animal models and biomarkers to study the 
impact of environmental stressors on breast cancer, 

o molecular epidemiology and exposure assessment research focused on studying 
important gene B environment interactions,

o inclusion of community concerns into breast cancer research projects.  

More information about the workshops held can be found at 
http://www.niehs.nih.gov/external/bcancer/home.htm. Gaps in our knowledge in 
each of these important areas will be addressed in the collaborative projects 
of the Centers.  

Each Center will contain two collaborative research projects.  Collaborative 
Project 1 is entitled "Environmental Effects on the Molecular Architecture and 
Function of the Mammary Gland across the Lifespan" and will entail the conduct 
of collaborative experiments using relevant animal models on the normal 
development of the mammary gland using a systems biology approach, and effects 
of selected chemicals and other exposures (i.e. nutritional, social) on 
endpoints such as breast pathology and gene and protein expression at critical 
points in time.  Collaborative Project 2 will be entitled "Environmental and 
Genetic Determinants of Puberty" and will be a collaborative multi-site 
epidemiologic study of sexual maturation in young girls.  All study sites will 
use similar methods to collect data on markers of physiologic changes during 
the pubertal process, and assessment of environmental stressors of importance 
to future breast cancer risk, including lifestyle behaviors, nutrition and 
anthropometric markers, chemical, physical, and social exposures at home and 
school.  In addition, pooled analysis of genetic polymorphisms of interest 
will be included to fully explore relevant gene–environment interactions.  
Evidence of active gene pathways from the collaborative project investigating 
the molecular architecture of the breast will be considered when choosing 
genetic polymorphisms for study.  The study will be designed to increase our 
understanding of how exposures and physiologic changes occurring during 
critical windows of breast development may impact on future breast cancer 
risk.  

Research Scope

The Breast Cancer and the Environment Research Centers Program is intended to 
create a national network that will foster interaction and collaboration 
within and between centers.  Each center will include the expertise of a 
diverse array of individuals.  Partnerships among scientists, breast cancer 
advocates, community members, and health care providers will be required.  The 
active participation of the community and national breast cancer advocacy 
groups and other community or faith based organization will be expected 
throughout the Center, especially in activities which translate research 
findings into useful information for the public.  Evidence of such 
participation in activities of the Center and especially those that are 
involved with translating research findings to the public will be required and 
reviewed as part of the application package.  Collaborations between NIEHS 
Environmental Health Sciences Centers and NCI-supported Comprehensive Cancer 
Centers, NCI-supported Breast Cancer Specialized Programs of Research 
Excellence (SPORE), and Department of Defense Breast Cancer Program-supported 
investigators are encouraged. 

Description of a Center

The Breast Cancer and the Environment Research Centers should be viewed as 
formal organizational components within the institution relative to other such 
existing research components at the institution.  Reasonable institutional 
support should be available to maintain the visibility, credibility and 
promote interactions with other such units at the host institution.  The 
reporting, accountability, and management structure of the Center within the 
institution should be equivalent to that of comparable organizations within 
the institution.  Cost sharing when appropriate is encouraged. 

Administrative Core (approximately four to five percent of budget in years one 
to seven)

Each Center will have two required core activities, an Administrative Core and 
a Community Outreach and Translation Core.  The Principal Investigator of the 
Center will be the Administrative Core director.  This core will serve as the 
central coordinating body of the Center.  Activities that will be directed 
from the Administrative Core will include:  

o Coordination of all Center research, meeting attendance, and other 
activities.

o Travel support for Steering Committee, subcommittee, network and scientific 
meetings.

o Support for seminars or other program enhancement activities which support 
awareness and interest in topics related to breast cancer and the environment.

Community Outreach and Translation Core (approximately four to five percent of 
budget in years one to seven)

The function of the Community Outreach and Translation Core (COTC) is to 
develop and implement strategies to translate the scientific findings of the 
center into information for the public and policy makers and to determine if 
they are effective.  These activities can include: developing educational 
materials for children and adults about breast cancer and the environment, 
conducting environmental justice related activities, conducting public 
awareness forums, workshops, and meetings with stakeholders to discuss a 
variety of issues, or to develop and evaluate novel approaches to disseminate 
research findings to interested parties.  COTC activities can also explore 
areas of concern or interest to the community.  For example, ethical issues 
pertinent to understanding the risks of exposure to environmental pollution, 
or using new early biomarkers of exposure or breast cancer risk in research.  
The Center should develop a specific plan and set of integrated activities for 
COTC, particularly with respect to the Center=s needs to partner with 
community and target groups.  COTC should be a logical outgrowth of the 
scientific focus of the Center and exhibit the potential for mutual benefit 
due to interactions with Center research cores and investigators.  The COTC 
may be useful, for example, as a means of establishing a productive 
relationship with a community-based organization, which could subsequently 
form the foundation of a successful implementation of the research projects 
that are part of the Center.  The program should not go beyond public and 
community education about reducing environmental disease risk and/or hazard 
exposure recognition as the COTC is not intended to give medical, legal, 
political, social, or economic advice. 

Collaborative Projects  

Collaborative Project 1 (CP-1)(approximately 35-45 percent of budget in years 
one to seven)

Collaborative Project 1 is entitled "Environmental Effects on the Molecular 
Architecture and Function of the Mammary Gland across the Lifespan."  The 
purpose of this project is to conduct collaborative experiments using relevant 
animal and cell culture models of mammary gland development over the lifespan 
integrating endpoints such as gene expression, proteomics, and metabonomics, 
in order to understand the effects of selected chemicals or other 
environmental exposures on mammary gland pathology in these windows of time.  

Two main foci guiding this program will include:  

o exploration of in vitro and in vivo model systems (including cell culture 
and rodent models) for understanding mammary gland development and changes 
over the life span including the evaluation of critical windows of sensitivity 
to environmental agents, 

o evaluation and selection of potential environmental exposures for further 
study in appropriate animal or other model systems, via the use of in vitro 
mechanism-based screens to detect agents that possess signatures indicative of 
possible mammary gland carcinogenicity.   

It is anticipated that in the course of this work new and novel biomarkers of 
altered structure and function will be developed.  The development, validation 
and integration of new and enhanced mechanism-based screening paradigms are 
also encouraged. The choice and/or methods to characterize endpoints of 
interest will be left to the applicant but may include breast pathology, gene 
expression and protein expression profiles of relevant pathways and 
metabonomic profiles (urine and serum).  The goal of this work is to explore 
scientific hypotheses involved in mammary gland carcinogenesis and toxicologic 
responses during these windows. 

Proposals should include the conceptualization of an experimental framework 
and design for carrying out all aspects of this research.  Key hypotheses 
should be identified as well.  The application should include a proposal which 
defines the experimental approach and methods in the above mentioned two 
areas, identify and justify choice of appropriate endpoints of interest, time 
points across the lifespan, animal models and cell culture systems to be used, 
and data analysis strategies and techniques. 

Although the final design of the research will be agreed upon by consensus by 
the Breast Biology Subcommittee of the Steering Committee, it is critical that 
each applicant address both scientific foci in their application.  The 
Steering Committee will identify common research aims that all Centers will 
participate in and those aims that may be carried out locally by individual 
Centers.  

Overall the key areas of expertise needed to successfully conduct this project 
in a collaborative manner are: in vitro and in vivo mammary gland biology 
models, toxicology, pathology, genomics, proteomics, metabonomics and 
bioinformatics.  All expenses to conduct such work, including the use of 
appropriate facility cores, should be incorporated within the proposal for the 
collaborative project.  It is recognized that all areas of expertise or the 
capabilities to direct and perform all areas may not be resident at a single 
institution.  Centers may form collaborations or consortium for the purposes 
of obtaining needed expertise and capacity.  

Each Center will describe their abilities in each of the areas that are 
pertinent to their proposal.  A description of experience in each area of 
expertise delineated in the proposal, with publications to support it, should 
be included in the application.  It is not a requirement that any one Center 
have expertise in all of these areas.  After award, decisions will be made by 
the Steering Committee and the Program Director with regard to which Centers 
will take responsibility for specific scientific areas.  These decisions will 
be based on expertise and capacity to do the needed work as defined by the 
Breast Biology Subcommittee.  Budget adjustments may be necessary.  

Collaborative Project 2 (CP-2)(approximately 35-45 percent of budget in years 
one to seven)

Collaborative Project 2 will be entitled "Environmental and Genetic 
Determinants of Puberty" and will be a collaborative multi-site epidemiologic 
study of the young girls experiencing physiologic changes of thelarche and 
sexual maturation and their exposures that can impact on their future risk of 
breast cancer.  All study sites will use standardized methodologies to collect 
data on markers of breast development and other physiologic changes of sexual 
maturation, assessment of environmental stressors of importance to future 
breast cancer risk, including lifestyle behaviors, nutrition and dietary 
supplements, anthropometry, chemical and physical exposures at home, and 
school, and social factors.  DNA specimens will be collected, stored, and 
analyzed for relevant polymorphic variation related to pathways of interest in 
defining susceptibility.  

Each application should include a detailed study protocol with specific aims 
to address leading hypotheses (to include but not limited to gene
 – environment interactions), sample size calculations for individual study 
sites and combined analyses, definitions for enrolling study subjects and 
required follow-up time (if a longitudinal design is proposed), methods for 
collecting exposure data, health outcome data, and biological specimens.  
Inclusion of novel biomarkers of physiological changes in hormone status, 
breast development, ovarian and hormonal function, and other measures of 
skeletal and sexual maturation are encouraged.  After awards are made, the 
Epidemiology Subcommittee of the Steering Committee will integrate all of the 
meritorious study elements into one cohesive protocol that will be carried out 
at each Center.  

Centers should identify areas of expertise and capabilities in areas such as 
epidemiology, exposure assessment of chemicals and other exposures in 
biological and environmental media, biostatistics, clinical assessments, 
clinical laboratory determinations, and genetics, as proposed in their 
applications.  All expenses to conduct such work, including the use of 
appropriate facility cores, should be incorporated within the proposal for the 
collaborative project.  It is recognized that all areas of expertise or the 
capabilities to direct and perform all areas may not be resident in each 
Center.  Centers may form collaborations or consortium for the purposes of 
obtaining needed expertise and capacity.  After award, decisions will be made 
by the Steering Committee and the Program Director with regard to which 
Centers will take responsibility of specific scientific areas, i.e. chemical 
exposure assessment, dietary analysis, hormone analysis.  A description of 
such experience in each area of expertise, with publications to support it, 
should be included in the application.  These decisions will be based on 
expertise and capacity to do the needed work.  Budget adjustments may be 
necessary.

Although it is unlikely that any individual study site will have enough power 
to study in detail relevant gene-environment interactions, applicants are to 
include and justify such hypotheses to be evaluated for the combined analyses 
of data.  All Centers will maintain a repository of stored biological and 
environmental specimens for later analysis.  Analyses may include analytical 
chemistry to determine body burdens of chemical exposures. Hormone analysis, 
and genetic analysis should be incorporated into the proposal study design.  
The Epidemiology Subcommittee will decide over the course of the study which 
analyses are necessary.  

MECHANISM OF SUPPORT

This RFA will use the NIH U01 award mechanism.  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  The anticipated award date is 
July, 2003.  

The NIH U01 is a cooperative agreement award mechanism in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIEHS staff 
being substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award."  At this time, it is unknown if this RFA will be reissued after the 
initial program period.

FUNDS AVAILABLE

The NIEHS and NCI intend to commit approximately up to $5 million dollars up 
(total costs, including facilities and administrative costs) in Fiscal Year 03 
to fund three new grants in response to this RFA.  An applicant may request a 
project period of up to seven years and a budget for direct costs of up to 
$900,000 per year. Should an applicant plan to include subcontracts to other 
institutions or organizations, only the direct costs associated with the 
subcontracts will be used to tally the direct costs that apply toward the cap. 
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size of each award may 
also vary.  Although the financial plans of the NIEHS and NCI include funds to 
provide support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficient number of 
meritorious applications.   

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the following 
characteristics:

o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic institutions.  Applications will not be accepted from foreign 
institutions, however, foreign institutions may establish sub-contract 
arrangements with domestic applicant institutions.

Partnerships between researchers and members of community based organizations, 
faith based organizations and grass roots advocacy organizations that are 
concerned with breast cancer are required.  Applications that do not include 
such partnerships will be returned as non-responsive. 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with his or her institution to 
develop an application for support.  Individuals from under represented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS 

Awards made under this program must be interdisciplinary efforts bringing 
together investigators from different scientific disciplines.  In order to be 
funded, each applicant must successfully meet the requirements as stated 
below:

o Center Director should be a well-recognized scientist in the field of 
mammary gland biology or environmental health sciences.  The Center Director 
is expected to work to provide stewardship and balance to the overall program 
as it develops, conducts and reports on research conducted under the Center 
umbrella. 

o It is expected that a wide variety of disciplines will be represented in the 
expertise of the Center.  Applicants should include expertise in mammary gland 
biology and carcinogenesis, environmental health sciences and toxicology, 
molecular biology, epidemiology, exposure assessment, biostatistics, and 
community based participatory research.  Clinical expertise is also encouraged 
as part of the Center.  

o Proposals for two collaborative projects.  

o Investigators who are named as part of the two collaborative projects will 
be expected to work together with the other centers on the research.  This 
will entail participating in multiple planning and implementation meetings of 
each collaborative project during the first year.  Methods and approaches will 
be decided upon by consensus.  Less frequent meetings are envisioned after the 
collaborative projects are launched, but there will be a minimum of two such 
meetings a year for each collaborative project committee in years two to 
seven.    

o Each year the Centers will be involved in planning one scientific 
workshop/conference on emerging issues in breast cancer and the environment.  
The location of such a meeting and primary logistical support for the meeting 
will rotate across the centers.  A planning committee with scientific and 
community members from each center will be formed each year and will be 
charged with carrying out this task.  NIEHS and NCI program staff will provide 
assistance to this effort. 

Cooperative Agreement Terms and Conditions of Award

The following terms and conditions will be incorporated into the U01 award 
statement, and will be provided to the Center Director and the awardee 
institutional official at the time of award. 

These special Terms of Award are in addition to, and not in lieu of, otherwise 
applicable OMB administrative guidelines, HHS Grant Administration Regulations 
at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant Administration 
policy statements.  [Part 92 applies when state and local governments are 
eligible to apply as a "domestic organization."]

The administrative and funding instrument used for the applicants to this 
program is a cooperative agreement (U01), an "assistance" mechanism (rather 
than an "acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance 
of the activity.  Under the cooperative agreement, the NIH purpose is to 
support and/or stimulate the recipient's activity by involvement in and 
otherwise working jointly with the award recipient in a partner role, but it 
is not to assume direction, prime responsibility, or a dominant role in the 
activity.  Consistent with this concept, the dominant role and prime 
responsibility for the activity resides with the awardee for the project as a 
whole, although specific tasks and activities in carrying out the studies will 
be shared among the awardee and NIEHS and NCI through the Steering Committee.

1. Definitions

NETWORK:  The Centers supported as a result of this RFA will form the basis of 
the network of Breast Cancer and the Environment Research Centers Program.  
These Centers will work collaboratively on two projects; "Defining the Effects 
of Environmental Exposures on the Molecular Architecture of the Mammary Gland 
over the Lifespan," and "Environmental and Genetic Determinants of Puberty."  
The network will work collaboratively on holding an annual meeting on emerging 
topics in breast cancer and the environment. 

NATIONAL ADVISORY BOARD:  A subcommittee of the National Advisory 
Environmental Health Sciences Council (NAEHSC) will be established, with ad 
hoc members as appropriate, to provide advice to the Director, NIEHS, related 
to this program.  Subcommittee members who are standing members of the NAEHSC 
will also have responsibility for the second level review of all applications 
for this program.  The subcommittee will provide advice on the topics to be 
considered at the annual workshop/conference in emerging areas in breast 
cancer and the environment.  This subcommittee will meet with the Steering 
Committee once a year to review progress and make recommendations about future 
directions for the program.

BREAST CANCER and the ENVIRONMENT TASK FORCE:  A group of federal program 
directors or scientists that can provide oversight and advice about the 
progress of the collaborative research projects.  These government scientists 
may also provide liaison to other federally supported resources, such as 
tissue repositories, animal model consortiums, or genomics databases.  This 
task force will meet with the grantees and may review materials and products 
of the research as needed to provide input.

2. Awardee Rights and Responsibilities

o The Center Director will coordinate project activities scientifically and 
administratively at the awardee institution and at the other sites that may be 
supported by sub-contracts to this award.  The Center Director of a U01 grant 
will have primary authority and responsibility to define objectives and 
approaches, and to plan, conduct, analyze, and publish results, 
interpretations, and conclusions of studies conducted under the terms and 
conditions of the cooperative agreement award.

o The Center Director will assume responsibility and accountability to the 
applicant organization officials and to the NIEHS and NCI for the performance 
and proper conduct of the research supported by the U01 in accordance with the 
terms and conditions of the award.

o The Center Director, and a member of the Community Outreach and Translation 
Core who represents the views and concerns of the breast cancer advocacy 
community, will serve, as voting members of the Steering Committee, and will 
attend the Steering Committee meetings and appropriate subcommittee meetings.

o The Center Director will be responsible for accepting and implementing 
the goals, priorities, procedures, and policies agreed upon by the Steering 
Committee.

o The Center Director of a U01 will be responsible for close coordination 
and cooperation with the other components of the Network, the Steering 
Committee, and with the NIEHS and NCI staff.

o The Center Director will submit periodic progress reports in a standard 
format, as determined by the NIEHS and NCI.

o Awardees will retain custody of, and have primary rights to, the data 
developed under these awards at their institution, subject to Government 
rights of access consistent with current HHS, PHS, and NIH policies.  They 
will also share these data with other Centers as needed. The policy of the PHS 
is to make available to the public the results and accomplishments of the 
activities that it funds.  The Center Director agrees to data sharing and data 
pooling practices as designed by the Steering Committee and subcommittees. 

o The Center Director is responsible for effective communication and 
collaboration  with the Network.  There will be sharing of data and other 
information among the Centers and between the Centers and the NIEHS and NCI.  
Awardees are responsible for developing or enhancing their Internet 
communication tools to ensure effective communication among the different 
components that form the U01 grant (such as, sub-contracts, individual core 
facilities at the institution), the other Centers, and with NIEHS and NCI.

3. Extramural Staff Responsibilities

o The NIEHS and NCI Program Directors will provide normal stewardship for the 
U01 awards under this RFA. The NIEHS and NCI Program Directors will review the 
scientific progress of individual U01s, and review them for compliance with 
the operating policies developed by the Steering Committee.  The NIEHS and NCI 
Program Directors may recommend withholding support, re-allocating support 
among awardees, and suspension or termination of a U01 award for lack of 
scientific progress or failure to adhere to policies established by the 
Steering Committee.  

o The NIEHS and NCI Coordinators will have substantial scientific and 
programmatic involvement to assist, guide, coordinate, and participate in the 
conduct of the Network activities.  The NIEHS and NCI Coordinators will 
coordinate and facilitate the Network activities, will attend and participate 
in all meetings of the Steering Committee and subcommittees, and will provide 
liaison between the Steering Committee, the Network and the NIEHS/NCI/NIH and 
other federal agencies as needed.  The NIEHS and NCI Coordinators along with 
supporting staff will work with the Network to facilitate one 
conference/workshop per year on emerging topics in breast cancer and the 
environment. 

o The NIEHS and NCI Coordinators will coordinate meetings and activities that 
involve the network of Centers, the Steering Committee, and the National 
Advisory Environmental Health Sciences Council subcommittee on breast cancer 
and the environment.  The NIEHS and NCI Coordinators will regularly consult 
with the Breast Cancer and the Environment Task Force on the scientific 
progress of the Network.  Task force members will have access to progress 
reports and other relevant information submitted by the U01 awardees.   

o The NIEHS and NCI Coordinators will assist the Steering Committee in 
developing and drafting operating policies and policies for dealing with 
recurring situations that require a coordinated action. 

o Federal government staff with relevant scientific expertise or who manage 
research grant programs that relate scientifically to the goals of the network 
will form the Breast Cancer and the Environment Task Force.  The Task Force 
will meet regularly to review the progress of the Network and to recommend to 
the NIEHS and NCI Program Directors scientific developments and opportunities 
that may enhance the achievement of the network goals. 

o The NIEHS and NCI Program Directors may also function as the NIEHS and NCI 
Coordinators for this program. 

4. Collaborative Responsibilities

Upon acceptance of an award, investigators agree to participate in the 
cooperative nature of the Network and to work collaboratively on two research 
projects.  Investigators agree to exchange information freely within the 
Network and publish in the scientific literature according to procedures that 
the Steering Committee puts into place. Investigators agree to participate in 
all meetings necessary to further the collaborative goals of the program. 

5. Steering Committee

o An arbitration system, as detailed below, will be available to resolve 
disagreements between the NIEHS and NCI Program Directors and the members of 
the Steering Committee.

o The Steering Committee will be the main governing board of the Network.  It 
will function to set priorities for Centers program and its collaborative 
projects.  

o The Steering Committee will be composed of the director and a member of the 
Community Outreach and Translation Core who represents the views and concerns 
of the breast cancer advocacy community from each U01.  The two 
representatives from each U01 will each have one Steering Committee vote.  The 
chairperson, who will be someone other than an NIEHS/NCI/NIH staff member, 
will be selected by the Steering Committee.  The NIEHS and NCI Program 
Directors are non-voting members of the Steering Committee, and will 
facilitate creation of the group and will attend all meetings.  NIH staff may 
not serve as the Committee chair.

o The Steering Committee may, when it deems it to be necessary, invite 
additional, non-voting scientific advisors to the meetings at which research 
priorities and opportunities are discussed.  The NIEHS and NCI reserves the 
right to augment the scientific or consumer expertise of the Network when 
necessary.

o There will be one Steering Committee meeting annually.  The initial planning 
meeting will be organized by NIEHS and NCI, but subsequent meetings will be 
organized by the Steering Committee.  The committee=s chair will schedule the 
meetings and will be responsible for meeting agendas (in collaboration with 
the Program Director), chairing the meetings, and producing Steering 
Committee=s reports.  The same procedure will take place for the two 
subcommittees of the Steering Committee.  Chairs will be selected and 
responsibilities with regard to agenda planning, chairing the meetings, and 
producing reports will follow the model of the Steering Committee.    

o There will be two subcommittees of the Steering Committee, the Breast 
Biology Subcommittee and the Epidemiology Subcommittee.  Each subcommittee 
will plan and implement the collaborative projects.  The Breast Biology 
Subcommittee will be comprised of the necessary senior investigators from CP-1 
in each center, and the Epidemiology Subcommittee will be comprised of the 
necessary senior investigators from CP-2 in each center.  Each Center will 
designate one member of the Community Outreach and Translation Core who can 
represent the views and the concerns of the breast cancer advocacy community 
to participate in each subcommittee.  Each subcommittee will designate a 
chair, who, in addition to directing the activities of the subcommittee, will 
keep the NIEHS program director and Steering Committee apprised of progress of 
their respective collaborative project.  Each subcommittee will meet as needed 
by conference call, videoconference or in person and will report to the 
Steering Committee annually.  It is estimated that each subcommittee will each 
meet face-to-face up to four times in the first year of each collaborative 
project.  The initial planning meeting will take place in the Research 
Triangle Park, NC, with subsequent meetings at a location that the Steering 
Committee/subcommittees select and with which the NIEHS and NCI concur.  The 
NIEHS and NCI Program Directors or their designee(s) will attend all 
subcommittee meetings. NIH representation on the Steering Committee will never 
make up a majority of the total number.

o The first meeting of the Network will be a Planning Meeting, which will take 
place in the Research Triangle Park, NC, very shortly after the awards are 
finalized.  At the Planning Meeting, the Steering Committee and subcommittees 
will be formed and select chairpersons from among the members who represent 
the U01 awardees.  Steering Committee will also draft and agree to: the terms 
of a charter to detail policies and procedures, a process for monitoring 
compliance with the policies and procedures, and a process for recommending 
that the NIEHS and NCI Program Directors act on evidence of non-compliance of 
any Consortium component with Steering Committee policies.

o The Steering Committee will work collaboratively to hold one 
workshop/conference a year, to which non-Network participants and the general 
public may be invited to enable the Network to explore scientific or 
technological innovations that occurs during the course of the project.  These 
meetings will also serve to inform the research and interested public of the 
progress of the Centers.  The organization of the workshops and symposia will 
be the responsibility of the Network members.  NIEHS and NCI may choose to 
provide supplemental funds to the selected host institution, after the receipt 
of an appropriate application and review by the Steering Committee.

o The Steering Committee may establish additional subcommittees.  The NIEHS 
and NCI Program Directors and the other NIEHS/NCI/NIH staff may serve on 
subcommittees, as they deem appropriate.

5. Arbitration Process

Any disagreement that may arise on scientific/programmatic matters (within the 
scope of the U01 award), between U01 awardees and the NIEHS and NCI may be 
brought to arbitration.  An arbitration panel will be composed of three 
members: one selected by the Steering Committee (without NIH representatives 
voting), or by the individual U01 awardee in the event of an individual 
disagreement; a second member selected by the NIEHS and NCI; and, the third 
member selected by the two prior selected members.  For U01 awardees, this 
special arbitration procedure in no way affects the awardees' right to appeal 
an adverse action that can otherwise be appealed in accordance with the PHS 
regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16.

6. Yearly Milestones and Evaluations

Awardees will finalize yearly milestones at the time of their awards.  The 
awardees= milestones will be provided to the Steering Committee.  It is 
expected that the milestones will be adjusted annually at the award 
anniversary dates, both to incorporate a group=s scientific accomplishments 
and progress in the field in general, as well as to reflect the 
recommendations of the Steering Committee.  In accord with the procedures 
described above, NIH may withhold or reduce funds for projects that 
substantially fail to meet their milestones or to maintain their research 
activities as state-of-the-art.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas: scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Gwen W. Collman, Ph.D.
Scientific Program Administrator
Chemical Exposures and Molecular Biology Branch
National Institute of Environmental Health Sciences
P.O. Box 12233 111 T.W. Alexander Drive (MD EC-21)
Research Triangle Park, NC 27709
Telephone:  (919) 541-4980    
Fax:  (919) 316-4606
Email: collman@niehs.nih.gov

Kumiko Iwamoto, M.D., Dr.P.H.
Epidemiology and Genetics Research Program
National Cancer Institute
6130 Executive Boulevard, Room 5115
Bethesda, MD  20892-7324
Telephone:  (301) 435-4911
Fax:  (301) 402-4279
Email:  iwamotok@mail.nih.gov

o Direct your questions about peer review issues to:

Sally Eckert-Tilotta, Ph.D.
Scientific Review Administrator
Scientific Review Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-30
Research Triangle Park, NC 27709
Telephone: (919) 541-4446   
Fax: (919) 541-2503 
E-mail: eckertt1@niehs.nih.gov

o Direct your questions about financial or grants management matters to:

Ms. Lerlita Garcia
Grants Management Specialist
Grants Management Branch
National Institute of Environmental Health Sciences
P. O. Box 12233, MD EC-22
Research Triangle Park, NC 27709
Telephone:  (919) 316-4638  
Fax:  (919) 541-2860
Email:  garcia1@niehs.nih.gov

Ms. Crystal Wolfrey
Team Leader, DCCPS Team
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd, Suite 243
Bethesda, MD  20892 (for regular mail)
Rockville, MD 20852 (for hand-delivered mail)
Telephone:  (301) 496-8634
Fax:  (301) 496-8601
Email:  wolfreyc@gab.nci.nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel in each collaborative project and cores
o Participating institutions
o Number and title of this RFA

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NIEHS staff to estimate the potential review workload and plan 
the review.

The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to:

Sally Eckert-Tilotta, Ph.D.
Scientific Review Administrator
Scientific Review Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P. O. Box 12233, MD EC-30
Research Triangle Park, NC 27709
Telephone: (919) 541-4446    
Fax: (919) 541-2503 
E-mail: eckertt1@niehs.nih.gov

Courier Service Address:

Building 4401, Room 3171
79 TW Alexander Drive
Research Triangle Park, NC 27709

SUBMITTING AN APPLICATION 

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001.)  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
form.  For further assistance contact Grants Info, telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov

SUPPLEMENTAL INSTRUCTIONS

The body of the scientific application will be composed of the following 
sections with the appropriate page limitations:

- Introduction and organization of Center B 5 pages maximum
- Administrative Core - 15 pages maximum
- Community Outreach and Translation Core - 20 pages maximum
- Collaborative Project 1 - 25 pages maximum
- Collaborative Project 2 - 25 pages maximum
- Appendices 

Human subjects and animal welfare issues should be addressed in each of the 
appropriate sections.  Discussions of these issues will not be subject to the 
page limitations.  An overall Center description, list of all performance 
sites, and list of all key personnel (i.e., PHS 398 Form Page 2) should be 
included at the beginning of the application.  Appropriate budget pages for an 
overall consolidated Center budget, including consortium or contractual 
arrangements, should appear at the beginning of the application.  Budget 
pages, personnel descriptions and biosketches specific to the Cores and 
Collaborative Projects should be incorporated in the appropriate sections.  
All appendices should be labeled appropriately and should appear at the end of 
the proposal, after the checklist. Applications not organized in this manner 
may be returned without review.
 
USING THE RFA LABEL

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title, "Breast Cancer and the 
Environment Research Centers," and number, RFA ES-03-001, must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.  The RFA label is available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf 

SENDING AN APPLICATION TO THE NIH

Submit a signed, typewritten original of the application, including the 
checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710


BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be 
sent to:

Sally Eckert-Tilotta, Ph.D.
Scientific Review Administrator
Scientific Review Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-30
Research Triangle Park, NC 27709
Telephone: (919) 541-4446    
Fax: (919) 541-2503 
E-mail: eckertt1@niehs.nih.gov

Courier Service Address:

Building 4401, Room 3171
79 TW Alexander Drive
Research Triangle Park, NC 27709

APPLICATION PROCESSING

Applications must be received by the application receipt date listing in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an Introduction addressing the previous critique.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIEHS and NCI.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIEHS in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will:

o Receive a written critique.

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score.

o Receive a second level review by the National Advisory Environmental Health 
Sciences Council and National Cancer Advisory Board.
 
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following aspects 
of your application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals:
    
- Significance
- Approach
- Innovation
- Investigator
- Environment

The scientific review group will address and consider each of these criteria 
in assigning your application=s overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move a 
field forward.

OTHER REVIEW CRITERIA

A. Overall Center

Centers must include proposals for collaborative research projects with a 
conceptual theme focusing on breast cancer and the environment as outlined in 
the RFA.  There must be evidence of the potential for a meaningful 
interdisciplinary collaboration between a multiple areas of science and 
community based advocacy groups which are concerned with breast cancer. 
 
o Evaluate the interdisciplinary nature of the proposed research activities, 
integration of the projects around an overarching theme, and plans to 
effectively pursue interdisciplinary research objectives.

o Evaluate the plans for active participation of breast cancer advocacy groups 
and other relevant community groups in the conceptualization, planning, 
implementation, and handling and dissemination of research and findings 
whenever appropriate. 

o Evaluate how Center scientists propose to work collaboratively within the 
Center, across centers as needed for the completion of the two collaborative 
projects, and across Centers to enhance research opportunities being explored 
in investigator initiated activities.
 
B. Collaborative Projects

Environmental Effects on the Molecular Architecture of the Breast Across the 
Lifespan

o Judge the innovation and appropriateness of the scientific hypotheses, 
research approaches and methodology proposed to make a significant 
contribution to the field of study. 

o Evaluate the ability of the applicant group to contribute sufficiently to 
the collaborative efforts in the each of the needed areas of expertise (ie. 
animal models/pathology, genomics, proteomics, bioinformatics.)  Strengths and 
weaknesses in areas will be described.    

o Evaluate the resources available at the institution (instrumentation, space, 
capacity) to handle the work load of the collaborative project as designed by 
the applicant. 

o Evaluate the abilities of the investigators to contribute meaningfully to 
the development and conduct of collaborative activities. 

Environmental and Genetic Determinants of Puberty

o Judge the innovation and appropriateness of the scientific hypotheses and 
research methods proposed to make a significant contribution to the field of 
study. 

o Evaluate the ability of applicant group to contribute sufficiently to the 
collaborative efforts by demonstrating the capacity to recruit and follow-up 
needed study subjects, design and employ appropriate exposure assessment 
methodologies for all potential risk factors, and collection, banking and 
analysis of biologic specimens. 

o Evaluate the contribution of biostatistical expertise available to the goals 
of the collaborative project. 

o Evaluate the contribution of expertise in molecular epidemiology to 
contribute to the collaborative efforts of studying gene-environment 
interactions as part of this study.       

C. Administrative Core

o Evaluate whether the lines of authority and the administrative structure 
are designed for effective center management.

o Evaluate the qualifications, responsibilities, and effectiveness of 
senior leaders.  Identify if the percent effort is appropriate.              

o Evaluate the duties and percent efforts of administrative staff of the 
center in terms of their qualifications and contributions to the specialized 
needs and conduct of the center's research activities.

D. Community Outreach and Translation Core (COTC)

o Evaluate the appropriateness of the proposed core activities with regard to 
the potential for engaging community support for Center research projects, 
adequate dissemination of study findings, and translation of research findings 
to public health action.  

o Evaluate the expertise of core members to fulfill the mission of the COTC. 

E. Institutional Commitment

o Evaluate the effectiveness of the Center as a formal organizational 
component within the institution relative to other organizational components. 
 
o Determine whether the reporting, accountability, and management structure of 
the Center within the institution are equivalent to that of comparable 
organizations within the institution.  Assess the adequacy of institutional 
procedures and plans for monitoring, evaluating, and assuming accountability 
for the general success of the Center. 

o Evaluate the specific resources provided by the institution such as 
personnel, appropriate facilities, financial support, and other forms of 
support that reflect the level of the institution's commitment to the 
functional stability, continuing development, and success of the Center.

ADDITIONAL REVIEW CRITERIA

In addition to the above criteria, your application will also be reviewed with 
respect to the following:

Protections: The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.

Inclusion: The adequacy of plans to include subjects from all racial and 
ethnic groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of subjects 
will also be evaluated. (See Inclusion Criteria included in the section on 
Federal Citations, below)

Data Sharing: The adequacy of the proposed plan to share data.

Budget: The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: December 31, 2002 
Application Receipt Date:  February 11, 2003
Peer Review Date:  April, 2003
Council Review:  May, 2003
Earliest Anticipated Start Date:  July, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review).
o Availability of funds.
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided indicating 
that inclusion is inappropriate with respect to the health of the subjects or 
the purpose of the research.  This policy results from the NIH Revitalization 
Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.  

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines@ on the Inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom on Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA. 
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application. 
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas.  This RFA, "Breast Cancer and the 
Environment Research Centers" is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No.93.113, 93.114, and 93.115, and is not subject tot he intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review. 
 
Awards are made under authorization of Sections 301 and 405 of the Pubic 
Health Service Act as amended (42 USC 241 and 284) and administered under NIH 
grants policies described at http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


H H S Department of Health
and Human Services

 
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