Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2020

01-06-2020 | Mood Disorders | Clinical trial

Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy

Authors: Karin Ribi, Weixiu Luo, Barbara A. Walley, Harold J. Burstein, Jacquie Chirgwin, Rafat H. Ansari, Muhammed Salim, Andre van der Westhuizen, Ehtesham Abdi, Prudence A. Francis, Stephen Chia, Vernon J. Harvey, Anita Giobbie-Hurder, Gini F. Fleming, Olivia Pagani, Angelo Di Leo, Marco Colleoni, Richard D. Gelber, Aron Goldhirsch, Alan S. Coates, Meredith M. Regan, Jürg Bernhard

Published in: Breast Cancer Research and Treatment | Issue 2/2020

Login to get access

Abstract

Purpose

Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials.

Methods

A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years.

Results

Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point.

Conclusion

Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.
Appendix
Available only for authorised users
Literature
5.
go back to reference Frechette D, Paquet L, Verma S, Clemons M, Wheatley-Price P, Gertler SZ, Song X, Graham N, Dent S (2013) The impact of endocrine therapy on sexual dysfunction in postmenopausal women with early stage breast cancer: encouraging results from a prospective study. Breast Cancer Res Treat 141(1):111–117. https://doi.org/10.1007/s10549-013-2659-y CrossRefPubMed Frechette D, Paquet L, Verma S, Clemons M, Wheatley-Price P, Gertler SZ, Song X, Graham N, Dent S (2013) The impact of endocrine therapy on sexual dysfunction in postmenopausal women with early stage breast cancer: encouraging results from a prospective study. Breast Cancer Res Treat 141(1):111–117. https://​doi.​org/​10.​1007/​s10549-013-2659-y CrossRefPubMed
15.
go back to reference Bernhard J, Luo W, Ribi K, Colleoni M, Burstein HJ, Tondini C, Pinotti G, Spazzapan S, Ruhstaller T, Puglisi F, Pavesi L, Parmar V, Regan MM, Pagani O, Fleming GF, Francis PA, Price KN, Coates AS, Gelber RD, Goldhirsch A, Walley BA (2015) Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. Lancet Oncol 16(7):848–858. https://doi.org/10.1016/S1470-2045(15)00049-2 CrossRefPubMedPubMedCentral Bernhard J, Luo W, Ribi K, Colleoni M, Burstein HJ, Tondini C, Pinotti G, Spazzapan S, Ruhstaller T, Puglisi F, Pavesi L, Parmar V, Regan MM, Pagani O, Fleming GF, Francis PA, Price KN, Coates AS, Gelber RD, Goldhirsch A, Walley BA (2015) Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. Lancet Oncol 16(7):848–858. https://​doi.​org/​10.​1016/​S1470-2045(15)00049-2 CrossRefPubMedPubMedCentral
16.
go back to reference Tevaarwerk AJ, Wang M, Zhao F, Fetting JH, Cella D, Wagner LI, Martino S, Ingle JN, Sparano JA, Solin LJ, Wood WC, Robert NJ (2014) Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 32(35):3948–3958. https://doi.org/10.1200/JCO.2014.55.6993 CrossRefPubMedPubMedCentral Tevaarwerk AJ, Wang M, Zhao F, Fetting JH, Cella D, Wagner LI, Martino S, Ingle JN, Sparano JA, Solin LJ, Wood WC, Robert NJ (2014) Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 32(35):3948–3958. https://​doi.​org/​10.​1200/​JCO.​2014.​55.​6993 CrossRefPubMedPubMedCentral
17.
go back to reference Ribi K, Luo W, Bernhard J, Francis PA, Burstein HJ, Ciruelos E, Bellet M, Pavesi L, Lluch A, Visini M, Parmar V, Tondini C, Kerbrat P, Perello A, Neven P, Torres R, Lombardi D, Puglisi F, Karlsson P, Ruhstaller T, Colleoni M, Coates AS, Goldhirsch A, Price KN, Gelber RD, Regan MM, Fleming GF (2016) Adjuvant tamoxifen plus ovarian function suppression versus tamoxifen alone in premenopausal women with early breast cancer: patient-reported outcomes in the suppression of ovarian function trial. J Clin Oncol 34(14):1601–1610. https://doi.org/10.1200/JCO.2015.64.8675 CrossRefPubMedPubMedCentral Ribi K, Luo W, Bernhard J, Francis PA, Burstein HJ, Ciruelos E, Bellet M, Pavesi L, Lluch A, Visini M, Parmar V, Tondini C, Kerbrat P, Perello A, Neven P, Torres R, Lombardi D, Puglisi F, Karlsson P, Ruhstaller T, Colleoni M, Coates AS, Goldhirsch A, Price KN, Gelber RD, Regan MM, Fleming GF (2016) Adjuvant tamoxifen plus ovarian function suppression versus tamoxifen alone in premenopausal women with early breast cancer: patient-reported outcomes in the suppression of ovarian function trial. J Clin Oncol 34(14):1601–1610. https://​doi.​org/​10.​1200/​JCO.​2015.​64.​8675 CrossRefPubMedPubMedCentral
21.
go back to reference Bredart A, Dolbeault S, Savignoni A, Besancenet C, This P, Giami A, Michaels S, Flahault C, Falcou MC, Asselain B, Copel L (2011) Prevalence and associated factors of sexual problems after early-stage breast cancer treatment: results of a French exploratory survey. Psychooncology 20(8):841–850. https://doi.org/10.1002/pon.1789 CrossRefPubMed Bredart A, Dolbeault S, Savignoni A, Besancenet C, This P, Giami A, Michaels S, Flahault C, Falcou MC, Asselain B, Copel L (2011) Prevalence and associated factors of sexual problems after early-stage breast cancer treatment: results of a French exploratory survey. Psychooncology 20(8):841–850. https://​doi.​org/​10.​1002/​pon.​1789 CrossRefPubMed
27.
go back to reference van Londen GJ, Beckjord EB, Dew MA, Cooper KL, Davidson NE, Bovbjerg DH, Donovan HS, Thurston RC, Morse JQ, Nutt S, Rechis R (2014) Associations between adjuvant endocrine therapy and onset of physical and emotional concerns among breast cancer survivors. Support Care Cancer 22(4):937–945. https://doi.org/10.1007/s00520-013-2041-y CrossRefPubMed van Londen GJ, Beckjord EB, Dew MA, Cooper KL, Davidson NE, Bovbjerg DH, Donovan HS, Thurston RC, Morse JQ, Nutt S, Rechis R (2014) Associations between adjuvant endocrine therapy and onset of physical and emotional concerns among breast cancer survivors. Support Care Cancer 22(4):937–945. https://​doi.​org/​10.​1007/​s00520-013-2041-y CrossRefPubMed
34.
go back to reference Den Oudsten BL, Van Heck GL, Van der Steeg AF, Roukema JA, De Vries J (2010) Clinical factors are not the best predictors of quality of sexual life and sexual functioning in women with early stage breast cancer. Psychooncology 19(6):646–656. https://doi.org/10.1002/pon.1610 CrossRef Den Oudsten BL, Van Heck GL, Van der Steeg AF, Roukema JA, De Vries J (2010) Clinical factors are not the best predictors of quality of sexual life and sexual functioning in women with early stage breast cancer. Psychooncology 19(6):646–656. https://​doi.​org/​10.​1002/​pon.​1610 CrossRef
36.
go back to reference Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, TEXT, and SOFT Investigators; International Breast Cancer Study Group (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371(2):107–118. https://doi.org/10.1056/NEJMoa1404037 CrossRefPubMedPubMedCentral Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, TEXT, and SOFT Investigators; International Breast Cancer Study Group (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371(2):107–118. https://​doi.​org/​10.​1056/​NEJMoa1404037 CrossRefPubMedPubMedCentral
37.
go back to reference Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD, SOFT Investigators; International Breast Cancer Study Group (2015) Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 372(5):436–446. https://doi.org/10.1056/NEJMoa1412379 CrossRefPubMed Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD, SOFT Investigators; International Breast Cancer Study Group (2015) Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 372(5):436–446. https://​doi.​org/​10.​1056/​NEJMoa1412379 CrossRefPubMed
38.
go back to reference Sherbourne CD (1992) Social functioning: sexual problems measures. In: Stewart AL, Ware JE (eds) Measuring functioning and well-being: the medical outcomes study approach. Duke University Press, Durham, pp 194–204 Sherbourne CD (1992) Social functioning: sexual problems measures. In: Stewart AL, Ware JE (eds) Measuring functioning and well-being: the medical outcomes study approach. Duke University Press, Durham, pp 194–204
40.
go back to reference Ganz PA, Cecchini RS, Julian TB, Margolese RG, Costantino JP, Vallow LA, Albain KS, Whitworth PW, Cianfrocca ME, Brufsky AM, Gross HM, Soori GS, Hopkins JO, Fehrenbacher L, Sturtz K, Wozniak TF, Seay TE, Mamounas EP, Wolmark N (2016) Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 387(10021):857–865. https://doi.org/10.1016/S0140-6736(15)01169-1 CrossRefPubMed Ganz PA, Cecchini RS, Julian TB, Margolese RG, Costantino JP, Vallow LA, Albain KS, Whitworth PW, Cianfrocca ME, Brufsky AM, Gross HM, Soori GS, Hopkins JO, Fehrenbacher L, Sturtz K, Wozniak TF, Seay TE, Mamounas EP, Wolmark N (2016) Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 387(10021):857–865. https://​doi.​org/​10.​1016/​S0140-6736(15)01169-1 CrossRefPubMed
42.
go back to reference Bernhard J, Hurny C, Coates AS, Peterson HF, Castiglione-Gertsch M, Gelber RD, Goldhirsch A, Senn HJ, Rudenstam CM (1997) Quality of life assessment in patients receiving adjuvant therapy for breast cancer: the IBCSG approach. The International Breast Cancer Study Group. Ann Oncol 8(9):825–835. https://doi.org/10.1023/A:1008269715091 CrossRefPubMed Bernhard J, Hurny C, Coates AS, Peterson HF, Castiglione-Gertsch M, Gelber RD, Goldhirsch A, Senn HJ, Rudenstam CM (1997) Quality of life assessment in patients receiving adjuvant therapy for breast cancer: the IBCSG approach. The International Breast Cancer Study Group. Ann Oncol 8(9):825–835. https://​doi.​org/​10.​1023/​A:​1008269715091 CrossRefPubMed
44.
go back to reference Bernhard J, Zahrieh D, Castiglione-Gertsch M, Hurny C, Gelber RD, Forbes JF, Murray E, Collins J, Aebi S, Thurlimann B, Price KN, Goldhirsch A, Coates AS, International Breast Cancer Study Group Trial V (2007) Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients—the International Breast Cancer Study Group Trial VIII. J Clin Oncol 25(3):263–270. https://doi.org/10.1200/JCO.2005.04.5393 CrossRef Bernhard J, Zahrieh D, Castiglione-Gertsch M, Hurny C, Gelber RD, Forbes JF, Murray E, Collins J, Aebi S, Thurlimann B, Price KN, Goldhirsch A, Coates AS, International Breast Cancer Study Group Trial V (2007) Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients—the International Breast Cancer Study Group Trial VIII. J Clin Oncol 25(3):263–270. https://​doi.​org/​10.​1200/​JCO.​2005.​04.​5393 CrossRef
45.
go back to reference Radloff LS (1977) The CES-D Scale: a self-reported depression scale for research in the general population. Appl Psychol Meas 1:385–401CrossRef Radloff LS (1977) The CES-D Scale: a self-reported depression scale for research in the general population. Appl Psychol Meas 1:385–401CrossRef
47.
go back to reference von Hippel C, Rosenberg SM, Austin SB, Sprunck-Harrild K, Ruddy KJ, Schapira L, Come S, Borges VF, Partridge AH (2019) Identifying distinct trajectories of change in young breast cancer survivors' sexual functioning. Psychooncology 28(5):1033–1040. https://doi.org/10.1002/pon.5047 CrossRef von Hippel C, Rosenberg SM, Austin SB, Sprunck-Harrild K, Ruddy KJ, Schapira L, Come S, Borges VF, Partridge AH (2019) Identifying distinct trajectories of change in young breast cancer survivors' sexual functioning. Psychooncology 28(5):1033–1040. https://​doi.​org/​10.​1002/​pon.​5047 CrossRef
49.
go back to reference Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow DM, Sharer CW, Burton GV, Kuzma CS, Moseley A, Lew DL, Fisch MJ, Moinpour CM, Hershman DL, Wade JL 3rd (2018) Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. J Clin Oncol 36(4):326–332. https://doi.org/10.1200/JCO.2017.74.6651 CrossRefPubMed Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow DM, Sharer CW, Burton GV, Kuzma CS, Moseley A, Lew DL, Fisch MJ, Moinpour CM, Hershman DL, Wade JL 3rd (2018) Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. J Clin Oncol 36(4):326–332. https://​doi.​org/​10.​1200/​JCO.​2017.​74.​6651 CrossRefPubMed
50.
51.
go back to reference Carter J, Lacchetti C, Andersen BL, Barton DL, Bolte S, Damast S, Diefenbach MA, DuHamel K, Florendo J, Ganz PA, Goldfarb S, Hallmeyer S, Kushner DM, Rowland JH (2018) Interventions to address sexual problems in people with cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline. J Clin Oncol 36(5):492–511. https://doi.org/10.1200/JCO.2017.75.8995 CrossRefPubMed Carter J, Lacchetti C, Andersen BL, Barton DL, Bolte S, Damast S, Diefenbach MA, DuHamel K, Florendo J, Ganz PA, Goldfarb S, Hallmeyer S, Kushner DM, Rowland JH (2018) Interventions to address sexual problems in people with cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline. J Clin Oncol 36(5):492–511. https://​doi.​org/​10.​1200/​JCO.​2017.​75.​8995 CrossRefPubMed
54.
go back to reference Reichenpfader U, Gartlehner G, Morgan LC, Greenblatt A, Nussbaumer B, Hansen RA, Van Noord M, Lux L, Gaynes BN (2014) Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf 37(1):19–31. https://doi.org/10.1007/s40264-013-0129-4 CrossRefPubMed Reichenpfader U, Gartlehner G, Morgan LC, Greenblatt A, Nussbaumer B, Hansen RA, Van Noord M, Lux L, Gaynes BN (2014) Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf 37(1):19–31. https://​doi.​org/​10.​1007/​s40264-013-0129-4 CrossRefPubMed
55.
go back to reference Saha P, Regan MM, Pagani O, Francis PA, Walley BA, Ribi K, Bernhard J, Luo W, Gomez HL, Burstein HJ, Parmar V, Torres R, Stewart J, Bellet M, Perello A, Dane F, Moreira A, Vorobiof D, Nottage M, Price KN, Coates AS, Goldhirsch A, Gelber RD, Colleoni M, Fleming GF, SOFT; TEXT Investigators; International Breast Cancer Study Group (2017) Treatment efficacy, adherence, and quality of life among women younger than 35 years in the international breast cancer study group TEXT and SOFT adjuvant endocrine therapy trials. J Clin Oncol 35(27):3113–3122. https://doi.org/10.1200/JCO.2016.72.0946 CrossRefPubMedPubMedCentral Saha P, Regan MM, Pagani O, Francis PA, Walley BA, Ribi K, Bernhard J, Luo W, Gomez HL, Burstein HJ, Parmar V, Torres R, Stewart J, Bellet M, Perello A, Dane F, Moreira A, Vorobiof D, Nottage M, Price KN, Coates AS, Goldhirsch A, Gelber RD, Colleoni M, Fleming GF, SOFT; TEXT Investigators; International Breast Cancer Study Group (2017) Treatment efficacy, adherence, and quality of life among women younger than 35 years in the international breast cancer study group TEXT and SOFT adjuvant endocrine therapy trials. J Clin Oncol 35(27):3113–3122. https://​doi.​org/​10.​1200/​JCO.​2016.​72.​0946 CrossRefPubMedPubMedCentral
57.
go back to reference American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington DCCrossRef American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington DCCrossRef
58.
go back to reference World Health Organization (2004) International classification of diseases and health related problems. World Health Organization, Geneva World Health Organization (2004) International classification of diseases and health related problems. World Health Organization, Geneva
Metadata
Title
Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy
Authors
Karin Ribi
Weixiu Luo
Barbara A. Walley
Harold J. Burstein
Jacquie Chirgwin
Rafat H. Ansari
Muhammed Salim
Andre van der Westhuizen
Ehtesham Abdi
Prudence A. Francis
Stephen Chia
Vernon J. Harvey
Anita Giobbie-Hurder
Gini F. Fleming
Olivia Pagani
Angelo Di Leo
Marco Colleoni
Richard D. Gelber
Aron Goldhirsch
Alan S. Coates
Meredith M. Regan
Jürg Bernhard
Publication date
01-06-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05622-5

Other articles of this Issue 2/2020

Breast Cancer Research and Treatment 2/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine