Measurement of Estrogens and Estrogen Metabolites in Concurrently Collected Serum and Urine Samples from Premenopausal and Postmenopausal Women

National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG), The Epidemiology and Biostatistics Program (EBP), plans to procure on a sole source basis laboratory support services to measure estrogens and estrogen metabolites in serum and urine from Craft Technologies, 4344 Frank Price Church Road, Wilson NC 27893. The response close date of this notice for this requirement is in accordance with FAR 5.203(a)(1). This acquisition will be processed under FAR Part 12 - Acquisition for Commercial Items and in accordance with simplified acquisition procedures as stated in FAR Part 13.106-1(b)(1), and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 541380 and the business size standard is $15.0M. Only one award will be made as a result of this solicitation. This will be awarded as a firm fixed price type contract. It has been determined there are no opportunities to acquire green products or services for this procurement. The Division of Cancer Epidemiology and Genetics (DCEG) is a research program of the National Cancer Institute (NCI), one of the National Institutes of Health (NIH). The Division is the world's most comprehensive cancer epidemiology research group. Its renowned epidemiologists, geneticists, and biostatisticians conduct population and multidisciplinary research to discover the genetic and environmental determinants of cancer and new approaches to cancer prevention. The Division's research impacts public health policy in the United States and around the world. The National Cancer Institute (NCI) has developed a stable isotope dilution liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for measuring concurrently 15 estrogens and estrogen metabolites in human serum with high sensitivity, validity, and reproducibility (Xu X et al, Anal Chem 2007 79:7813-21). NCI has also developed a comparable LC-MS/MS assay for measuring the same 15 estrogens and estrogen metabolites in urine (Xu X et al, Anal Chem 2005 77:6646-54). Both unconjugated and total (unconjugated+conjugated) concentrations are measured in serum, but only total concentrations are measured in urine since nearly all estrogens/estrogen metabolites in urine are conjugated. The specific estrogens and estrogen metabolites measured include the parent estrogens (estrone and estradiol); metabolites in the 2-hydroxylation pathway (2-hydroxyestrone, 2-methoxyestrone, 2-hydroxyestradiol, 2-methoxyestradiol, and 2-hydroxyestrone-3-methyl ether); metabolites in the 4-hydroxylation pathway (4-hydroxyestrone, 4-methoxyestrone, and 4-methoxyestradiol); and metabolites in the 16-hydroxylation pathway (16a-hydroxyestrone, estriol, 17-epiestriol, 16-ketoestradiol, and 16-epiestriol). Laboratory and clinical studies have suggested that specific estrogen metabolism profiles and/or specific estrogen metabolites may play a role in breast cancer etiology. Development of these LC-MS/MS assays for estrogens/estrogen metabolites allowed for the first time robust tests of these hypotheses about estrogen metabolism in population studies. NCI investigators and collaborators have now published five cohort-based epidemiologic studies of breast cancer that utilize either the serum or urine estrogen/estrogen metabolite assay. Even though the detailed results of the individual studies differ, each of these studies suggests that estrogen metabolism may indeed contribute to breast cancer risk. Specifically, increased 2-hydroxylation of parent estrogens is significantly associated with reduced risk, possibly by promoting excretion of parent estrogens and bioactive estradiol. However, little is known about the interrelationships of circulating and urinary parent estrogen levels and estrogen metabolism patterns. NCI proposes to explore these relationships using concurrently collected serum and urine samples. Results will clarify whether an individual's estrogen metabolism profile is similar in serum and urine and whether specific serum estrogen metabolism profiles are associated with enhanced excretion of parent estrogens and estradiol. Results will also help us integrate and interpret the various cohort studies of estrogen metabolism and breast cancer that relied on either serum or urine samples. NCI will measure by LC-MS/MS estrogens and estrogen metabolites in serum and urine samples that have collected at the same time. A total of 125 postmenopausal and 75 premenopausal women, at different phases of the menstrual cycle, will be included. None of the women will have taken exogenous hormones or been pregnant or breast-fed in the last 12 months. Participants will be from the Harvard Nurses cohorts (Caucasian), the Johns Hopkins Medical Institutions breast and ovarian cancer screening program (Caucasian and Black), and the Shanghai Physical Activity Study (Chinese). Both total (conjugated+unconjugated) and unconjugated concentrations of estrogens/estrogen metabolites will be measured in serum; only total concentrations will be measured in urine since unconjugated forms are rare in urine. NCI will investigate the interrelationships, in serum and urine, of total estrogen, individual estrogens and estrogen metabolites, and estrogen metabolic pathway groupings. Absolute concentrations, ratios, and percent of total estrogen will be explored. The influence of menopausal status, age, BMI, and race will be assessed. NCI anticipates that unusually accurate and precise data will facilitate disentangling these complex relationships. To NCI knowledge, only one known laboratory, Craft Technologies, has developed an assay for the estrogens and estrogen metabolites in serum and urine with 1) sensitivity adequate to detect at least 15 estrogens and estrogen metabolites in postmenopausal women, 2) high reproducibility (? 10% coefficients of variation, including all steps of the procedure, for estrone, estradiol, and most of the estrogen metabolites), 3) demonstrated accuracy, based on calibration of the estradiol measurements with the Centers for Disease Control Hormone Standardization Program, and 4) low volume requirements (? 0.3 mL for each assay). Approximately 40 samples can be assayed in a week. Therefore, the assay is rapid enough to be used with the multiple samples required by a large epidemiologic study. Additionally, NCI awarded a contract previously to Craft Technologies for the development and validation of a LC-MS/MS assay for measuring estrogens and estrogen metabolites in serum and urine. Government Responsibilities The NCI shall ensure that the NCI ships the serum and urine samples to be assayed directly to the Contractor within three months after the award. Aliquots of 1.0 mL of serum and 500 microL of urine will be frozen at -70'C, packed with dry ice, and shipped, via overnight courier, to the Contractor. The NCI will provide the Contractor with an electronic manifest containing anonymized identification numbers for each sample at the time the samples are shipped. Contractor Requirements The Contractor shall: 1) Provide the current performance characteristics of the LC-MS/MS estrogen/estrogen metabolite assay in serum and urine, including accuracy, reproducibility, and sensitivity. 2) Measure unconjugated estrogens/estrogen metabolites and total estrogens/estrogen metabolites in 220 serum samples using an accurate, precise, sensitive LC-MS/MS method. 3) Measure total (unconjugated+conjugated) estrogens/estrogen metabolites in 220 urine samples using an accurate, precise, sensitive LC-MS/MS method. 4) Provide the results of the assays to the NCI Technical Point of Contact (TPC). Results shall be provided within one month of completion of the assays. Reporting Requirements and Deliverables The Contractor shall provide estrogen/estrogen metabolite concentrations for each of the 220 serum and 220 urine samples within one month of completing the assays. The report shall be submitted in a Microsoft-compatible electronic format to the TPC. The Contractor shall provide a description of any problems that develop during the assay procedures. The Contractor shall provide a brief description of the LC-MS/MS estrogen/estrogen metabolite assay methods, in serum and urine, and the current performance characteristics, including accuracy, reproducibility, and sensitivity. No residual sera need to be returned to the NCI. This notice is not a request for competitive quotation. However, if any interested party, especially small businesses, believes it can meet the above requirement, it may submit a capability statement, proposal, or quotation, which shall be considered by the agency. The statement of capabilities and any other information furnished must be in writing and must contain material in sufficient detail to allow the NCI to determine if the party can perform the requirement. Responses must be received in the contracting office by 4:00PM EDT, on Sept. 15, 2016. All responses and questions must be in writing and faxed (240) 276-5401 or emailed to Seena Ninan, Contracting Officer via electronic mail at ninans@mail.nih.gov. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. No collect calls will be accepted. In order to receive an award, Contractors must be registered and have valid, current Entity Record, including current Representations and Certifications, in the System for Award Management (SAM) through SAM.gov. Reference: N02CP66001-63 on all correspondence.