title: Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.
abstract: BACKGROUND
  For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.
  
  
  METHODS
  Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided.
  
  
  RESULTS
  The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses.
  
  
  CONCLUSIONS
  The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.). richardibcrf@gmail.com.
authors: Richard R
authors: RR
authors: Love
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Adriano V
authors: AV
authors: Laudico
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Nguyen
authors: N
authors: Van Dinh
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: D Craig
authors: DC
authors: Allred
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Gemma B
authors: GB
authors: Uy
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Le Hong
authors: le H
authors: Quang
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Jonathan Disraeli S
authors: JD
authors: Salvador
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Stephen Sixto S
authors: SS
authors: Siguan
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Maria Rica
authors: MR
authors: Mirasol-Lumague
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Nguyen Dinh
authors: ND
authors: Tung
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Noureddine
authors: N
authors: Benjaafar
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Narciso S
authors: NS
authors: Navarro
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Tran Tu
authors: TT
authors: Quy
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Arturo S
authors: AS
authors: De La Peña
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Rodney B
authors: RB
authors: Dofitas
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Orlino C
authors: OC
authors: Bisquera
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Nguyen Dieu
authors: ND
authors: Linh
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Ta Van
authors: TV
authors: To
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Gregory S
authors: GS
authors: Young
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: Erinn M
authors: EM
authors: Hade
authors: International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).
authors: David
authors: D
authors: Jarjoura
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004967:Estrogens / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008183:Luteal Phase; D008597:Menstrual Cycle; D016017:Odds Ratio; D010052:Ovariectomy; D017697:Premenopause; D011374:Progesterone / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004967:Estrogens; D013629:Tamoxifen; D011374:Progesterone