title: Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.
abstract: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment.
  
  
  
  Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for ≥ 1 year were treated with letrozole (2.5 mg) daily for ≥ 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR.
  
  
  
  The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naïve patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR.
  
  
  
  These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Lea K
authors.initials: LK
authors.lastname: Krekow
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Hellerstedt
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Rufus P
authors.initials: RP
authors.lastname: Collea
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Steven
authors.initials: S
authors.lastname: Papish
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Shrinivas M
authors.initials: SM
authors.lastname: Diggikar
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Regina
authors.initials: R
authors.lastname: Resta
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Svetislava J
authors.initials: SJ
authors.lastname: Vukelja
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Frankie Ann
authors.initials: FA
authors.lastname: Holmes
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Reddy
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fox
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Peck
authors.affiliation: Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Lina Asmar, Yunfei Wang, Patricia S. Fox, and Joyce O'Shaughnessy, US Oncology Research; Susan R. Peck, McKesson Specialty Health, The Woodlands; Lea K. Krekow, Texas Oncology-The Breast Care Center of North Texas, Bedford; Beth A. Hellerstedt, Texas Oncology-Austin Central, Austin; Shrinivas M. Diggikar, Texas Oncology-Arlington South, Arlington; Svetislava J. Vukelja, Texas Oncology/Tyler Cancer Center, Tyler; Frankie Ann Holmes, Texas Oncology-Houston Memorial City, Houston; Praveen K. Reddy, Texas Oncology Midland Allison Cancer Center, Midland; Joyce O'Shaughnessy, Texas Oncology at Baylor-Charles A. Sammons Cancer Center, Dallas, TX; Rufus P. Collea, New York Oncology Hematology-Albany Medical Center, Albany; Regina Resta, New York Oncology Hematology, Troy, NY; and Steven Papish, Hematology-Oncology Associates of Northern New Jersey, Morristown, NJ. Joyce.OShaughnessy@usoncology.com.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000188:drug therapy* / Q000503:physiopathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause / Q000097:blood; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000096:biosynthesis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D004958:Estradiol; D000077289:Letrozole; D005640:Follicle Stimulating Hormone