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Oncotarget. 2018 Aug 3;9(60):31664-31681. doi: 10.18632/oncotarget.25839. eCollection 2018 Aug 3.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Author information

1
Gynecology Department, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
2
Fleury Laboratories, São Paulo, Brazil.
3
Barretos Cancer Hospital (HCB), Barretos, Brazil.
4
Department of Surgery, Urology Unit, Human Reproduction Division, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
5
Department of Surgery, Surgical Gastroenterology Division, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
6
Clinical and Experimental Oncology Department, Hematology and Hemotherapy Division, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
7
Department of Medicine, Endocrinology Division, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
8
Biophysics Department, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
9
Department of Biochemistry and Tissue Biology, State University of Campinas (UNICAMP), Campinas, Brazil.
10
Nutrition Department, School of Public Health, University of São Paulo School of Medicine (FMUSP), São Paulo, Brazil.
11
Department of Obstetrics and Gynecology, University of São Paulo School of Medicine (HCFMUSP), São Paulo, Brazil.
12
Department of Pediatrics, Children's Hospital, University of São Paulo School of Medicine (HCFMUSP), São Paulo, Brazil.
13
Retrovirology Laboratory, Infectious Diseases Unit, Medicine Department, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil.
14
Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria.
15
Department of Gynecology, Meran Hospital, Meran, Italy.
16
Department of Gynecology, Brixen Hospital, Brixen, Italy.
17
Department of Obstetrics and Gynecology, Gynecological Oncology Unit, University of California Irvine (UCI), California, USA.

Abstract

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies. Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

KEYWORDS:

breast cancer; metabolism; prognosis; response; survival

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