Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole

Lea K. Krekow, Beth A. Hellerstedt, Rufus P. Collea, Steven Papish, Shrinivas M. Diggikar, Regina Resta, Svetislava J. Vukelja, Frankie Ann Holmes, Praveen K. Reddy, Lina Asmar, Yunfei Wang, Patricia S. Fox, Susan R. Peck, Joyce O'Shaughnessy

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Abstract

Purpose 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. Patients and Methods 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 folliclestimulating hormone (FSH) and E2 were measured at baseline and over 2 years.Ageneral linearmodel was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1594-1600
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number14
DOIs
StatePublished - May 10 2016

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letrozole
Recovery of Function
Incidence
Aromatase Inhibitors
Menstruation
Amenorrhea
Hormones
Drug Therapy
Estrogen Receptors
Breast Neoplasms
Tamoxifen
Therapeutics
Menopause
Serum
Cyclophosphamide
Estradiol

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Krekow, L. K., Hellerstedt, B. A., Collea, R. P., Papish, S., Diggikar, S. M., Resta, R., ... O'Shaughnessy, J. (2016). Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole. Journal of Clinical Oncology, 34(14), 1594-1600. https://doi.org/10.1200/JCO.2015.62.2985
Krekow, Lea K. ; Hellerstedt, Beth A. ; Collea, Rufus P. ; Papish, Steven ; Diggikar, Shrinivas M. ; Resta, Regina ; Vukelja, Svetislava J. ; Holmes, Frankie Ann ; Reddy, Praveen K. ; Asmar, Lina ; Wang, Yunfei ; Fox, Patricia S. ; Peck, Susan R. ; O'Shaughnessy, Joyce. / Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 14. pp. 1594-1600.
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title = "Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole",
abstract = "Purpose 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. Patients and Methods 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 folliclestimulating hormone (FSH) and E2 were measured at baseline and over 2 years.Ageneral linearmodel was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. Results 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-na{\"i}ve 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. Conclusion 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.",
author = "Krekow, {Lea K.} and Hellerstedt, {Beth A.} and Collea, {Rufus P.} and Steven Papish and Diggikar, {Shrinivas M.} and Regina Resta and Vukelja, {Svetislava J.} and Holmes, {Frankie Ann} and Reddy, {Praveen K.} and Lina Asmar and Yunfei Wang and Fox, {Patricia S.} and Peck, {Susan R.} and Joyce O'Shaughnessy",
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Krekow, LK, Hellerstedt, BA, Collea, RP, Papish, S, Diggikar, SM, Resta, R, Vukelja, SJ, Holmes, FA, Reddy, PK, Asmar, L, Wang, Y, Fox, PS, Peck, SR & O'Shaughnessy, J 2016, 'Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole', Journal of Clinical Oncology, vol. 34, no. 14, pp. 1594-1600. https://doi.org/10.1200/JCO.2015.62.2985

Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole. / Krekow, Lea K.; Hellerstedt, Beth A.; Collea, Rufus P.; Papish, Steven; Diggikar, Shrinivas M.; Resta, Regina; Vukelja, Svetislava J.; Holmes, Frankie Ann; Reddy, Praveen K.; Asmar, Lina; Wang, Yunfei; Fox, Patricia S.; Peck, Susan R.; O'Shaughnessy, Joyce.

In: Journal of Clinical Oncology, Vol. 34, No. 14, 10.05.2016, p. 1594-1600.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Incidence and predictive factors for recovery of ovarian function in amenorrheic women in their 40s treated with letrozole

AU - Krekow, Lea K.

AU - Hellerstedt, Beth A.

AU - Collea, Rufus P.

AU - Papish, Steven

AU - Diggikar, Shrinivas M.

AU - Resta, Regina

AU - Vukelja, Svetislava J.

AU - Holmes, Frankie Ann

AU - Reddy, Praveen K.

AU - Asmar, Lina

AU - Wang, Yunfei

AU - Fox, Patricia S.

AU - Peck, Susan R.

AU - O'Shaughnessy, Joyce

PY - 2016/5/10

Y1 - 2016/5/10

N2 - Purpose 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. Patients and Methods 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 folliclestimulating hormone (FSH) and E2 were measured at baseline and over 2 years.Ageneral linearmodel was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. Results 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. Conclusion 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.

AB - Purpose 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. Patients and Methods 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 folliclestimulating hormone (FSH) and E2 were measured at baseline and over 2 years.Ageneral linearmodel was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. Results 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. Conclusion 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.

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