title: The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study.
abstract: BACKGROUND
  Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).
  
  
  METHODS
  Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry.
  
  
  RESULTS
  Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients.
  
  
  CONCLUSIONS
  STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01304251 , March 2011.
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. S.de_Groot2@lumc.nl.
authors.forename: Stefanie
authors.initials: S
authors.lastname: de Groot
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. M.P.G.Vreeswijk@lumc.nl.
authors.forename: Maaike P G
authors.initials: MP
authors.lastname: Vreeswijk
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. M.J.P.SchoenmaekersWelters@lumc.nl.
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. G.Gravesteijn@lumc.nl.
authors.forename: Gido
authors.initials: G
authors.lastname: Gravesteijn
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. J.J.W.A.Boei@lumc.nl.
authors.forename: Jan J W A
authors.initials: JJ
authors.lastname: Boei
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. A.Jochems@lumc.nl.
authors.forename: Anouk
authors.initials: A
authors.lastname: Jochems
authors.affiliation: Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands. D.Houtsma@lumc.nl.
authors.forename: Daniel
authors.initials: D
authors.lastname: Houtsma
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. H.Putter@lumc.nl.
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. J.J.M.van_der_Hoeven@lumc.nl.
authors.forename: Jacobus J M
authors.initials: JJ
authors.lastname: van der Hoeven
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. J.W.R.Nortier@lumc.nl.
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.affiliation: Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands. H.Pijl@lumc.nl.
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. J.R.Kroep@lumc.nl.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004249:DNA Damage; D005215:Fasting; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010865:Pilot Projects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006657:Histones; D018719:Erb-b2 Receptor Tyrosine Kinases; C468783:H2AX protein, human