Influence Factors of Neoadjuvant Chemotherapy-Related Amenorrhea in Premenopausal Breast Cancer Women and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

FAN Xuejiao , WANG Rong , CHEN Jie , TIAN Chunxiang , ZENG Helin ,  LU Qing

Department of Thyroid and Breast Surgery， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;

Corresponding author：

LU Qing, Email: lqlq1963@163.com

Keywords：

Neoadjuvant chemotherapy; Breast cancer; Amenorrhea; Periodicity

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Objective 　To analyze the influence factors of amenorrhea in premenopausal breast cancer women treated with neoadjuvant chemotherapy and the relationship of neoadjuvant chemotherapy-related amenorrhea （NCRA） to down-staging of tumor.
Methods 　Two hundred and twenty-four premenopausal breast cancer patients undergoing neoadjuvant chemotherapy from March 2006 to March 2011 in this hospital were investigated retrospectively. The effects of age， chemotherapy regiment， ER/PR status， Her-2 status， and tamoxifen （TAM） on NCRA and recovery of menstru-ation were assessed. The average age of the patients who had accepted different chemotherapy cycles when NCRA occurred was described， and the effect of different chemotherapy cycles on recovery of menstruation was evaluated. Tumor volume change was estimated to analysis the relation between NCRA and tumor response to chemotherapy.
Results 　One hundred and sixty-six （74.11%） cases occurred NCRA， 40 （26.49%） cases returned to normal menstruation apart from 15 cases who had accepted oophorectomy or the luteinizing hormone-releasing hormone analog goserelin before menstrual status change. The results of univariate analysis and multivariate analysis indicated that the NCRA and menstruation recovery were both related to age at diagnosis （P＜0.001，P=0.001）， and only menstruation recovery was related to chemotherapy regiments （P＜0.001）. However， the NCRA and menstruation recovery were not related to ER/PR status， Her-2 status，and TAM （P＞0.05）. Chemotherapy cycles when NCRA occurred decreased with the increase of age， and wasn’t assoc-iated with menstruation recovery （P＞0.05）. There was no correlation between NCRA and downstage of tumor after neoadjuvant chemotherapy （P＞0.05）.
Conclusions 　Amenorrhea resulted from neoadjuvant chemotherapy in most of breast cancer patients， which occurs more commonly in elder ones with less chemotherapy cycles. Quite a few patients resume menses after NCRA， which is associated with age and chemotherapy regiments. NCRA doesn’t influence tumor response to chemotherapy.

Citation： FAN Xuejiao,WANG Rong,CHEN Jie,TIAN Chunxiang,ZENG Helin,LU Qing,.. Influence Factors of Neoadjuvant Chemotherapy-Related Amenorrhea in Premenopausal Breast Cancer Women and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(8): 856-861. doi: Copy

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2.	Bear HD. Neoadjuvant chemotherapy for operable breast cancer：individualizing locoregional and systemic therapy[J]. Surg OncolClin N Am， 2010， 19(3)：607-626.
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4.	Mauri D， Pavlidis N， Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer：a meta-analysis[J]. J Natl Cancer Inst， 2005， 97(3)：188-194.
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7.	Walshe JM， Denduluri N， Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer[J]. J Clin Oncol， 2006， 24(36)：5769-5779.
8.	Del Mastro L， Venturini M， Sertoli MR， et al. Amenorrhea indu-ced by adjuvant chemotherapy in early breast cancer patients：prognostic role and clinical implications[J]. Breast Cancer Res Treat， 1997， 43(2)：183-190.
9.	Knobf MT. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors[J].Oncologist， 2006， 11(2)：96-110.
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11.	Oktem O， Oktay K. Fertility preservation for breast cancer patients[J]. Semin Reprod Med， 2009， 27(6)：486-492.
12.	Lee S， Kil WJ， Chun M， et al. Chemotherapy-related amenorrhea in premenopausal women with breast cancer[J]. Menopause， 2009， 16(1)：98-103.
13.	Pérez-Fidalgo JA， Roselló S， García-Garré E， et al. Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients：the impact of addition of taxanes to anthracycline-based regimens[J]. Breast Cancer Res Treat， 2010， 120(1)：245-251.
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16.	Swain SM， Land SR， Ritter MW， et al. Amenorrhea in premeno-pausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial[J]. Breast Cancer Res Treat， 2009， 113(2)：315-320.
17.	Han HS， Ro J， Lee KS， et al. Analysis of chemotherapy-induced amenorrhea rates by three different anthracycline and taxane cont-aining regimens for early breast cancer[J]. Breast Cancer Res Treat， 2009， 115(2)：335-342.
18.	Tham YL， Sexton K， Weiss H， et al. The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane[J]. Am J Clin Oncol，.
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21.	Maltaris T， Weigel M， Mueller A， et al. Cancer and fertility preservation：fertility preservation in breast cancer patient[J]. Breast Cancer Res， 2008， 10(2)：206.
22.	Meirow D， Lewis H， Nugent D， et al. Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide：clinical importance and proposed accurate investigative tool[J]. Hum Reprod， 1999， 14(7)：1903-1907.
23.	Reh A， Oktem O， Oktay K. Impact of breast cancer chemotherapyon ovarian reserve：a prospective observational analysis by mens-trual history and ovarian reserve markers[J]. Fertil Steril， 2008，.
24.	Sukumvanich P， Case LD， Van Zee K， et al. Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment：a prospective study[J]. Cancer， 2010， 116(13)：3102-3111.
25.	Minisini AM， Menis J， Valent F， et al. Determinants of recovery from amenorrhea in premenopausal breast cancer patients receivingadjuvant chemotherapy in the taxane era[J]. Anticancer Drugs， 2009， 20(6)：503-507.
26.	Zekri JM， El-Helw LM， Purohit OP， et al. Epirubicin/vinorelbine adjuvant chemotherapy in young women with breast cancer is associated with preservation of menstrual function[J]. Clin Oncol (R Coll Radiol)， 2008， 20(7)：513-516.
27.	Miller JJ 3rd， Cole LJ. Changes in mouse ovaries after prolonged treatment with cyclophosphamide[J]. Proc Soc Exp Biol Med， 1970， 133(1)：190-193.
28.	Koyama H， Wada T， Nishizawa Y， et al. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer[J]. Cancer， 1977， 39(4)：1403-1409.
29.	Himelstein-Braw R， Peters H， Faber M. Morphological study of the ovaries of leukaemic children[J]. Br J Cancer， 1978， 38(1)：82-87.
30.	Ataya KM， Valeriote FA， Ramahi-Ataya AJ. Effect of cyclophosphamide on the immature rat ovary[J]. Cancer Res， 1989， 49(7)：1660-1664.
31.	Letterie GS. Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure[J]. Hum Reprod， 2004， 19(4)：831-837.
32.	Takei H， Kurosumi M， Yoshida T， et al. Neoadjuvant endocrine therapy of breast cancer：which patients would benefit and what are the advantages?[J]. Breast Cancer， 2011， 18(2)：85-91.
33.	Vanhuyse M， Fournier C， Bonneterre J. Chemotherapy-induced amenorrhea：influence on disease-free survival and overall survivalin receptor-positive premenopausal early breast cancer patients[J]. Ann Oncol， 2005， 16(8)：1283-1288.
34.	(5)：1635-1639.
35.	-317.
36.	， 30(2)：126-132.
37.	， 74(3)：175-192.

1. Beasley GM， Olson JA Jr. What’s new in neoadjuvant therapy for breast cancer?[J]. Adv Surg， 2010， 44：199-228.
2. Bear HD. Neoadjuvant chemotherapy for operable breast cancer：individualizing locoregional and systemic therapy[J]. Surg OncolClin N Am， 2010， 19(3)：607-626.
3. Ena G. Neoadjuvant therapy in breast cancer[J]. Rev Med Brux， 2011， 32(4)：243-246.
4. Mauri D， Pavlidis N， Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer：a meta-analysis[J]. J Natl Cancer Inst， 2005， 97(3)：188-194.
5. Sapunar F， Smith IE. Neoadjuvant chemotherapy for breast cancer[J]. Ann Med， 2000， 32(1)：43-50.
6. Anchan RM， Ginsburg ES. Fertility concerns and preservation in younger women with breast cancer[J]. Crit Rev Oncol Hematol，.
7. Walshe JM， Denduluri N， Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer[J]. J Clin Oncol， 2006， 24(36)：5769-5779.
8. Del Mastro L， Venturini M， Sertoli MR， et al. Amenorrhea indu-ced by adjuvant chemotherapy in early breast cancer patients：prognostic role and clinical implications[J]. Breast Cancer Res Treat， 1997， 43(2)：183-190.
9. Knobf MT. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors[J].Oncologist， 2006， 11(2)：96-110.
10. Hulvat MC， Jeruss JS. Maintaining fertility in young women with breast cancer[J]. Curr Treat Options Oncol， 2009， 10(5-6)：.
11. Oktem O， Oktay K. Fertility preservation for breast cancer patients[J]. Semin Reprod Med， 2009， 27(6)：486-492.
12. Lee S， Kil WJ， Chun M， et al. Chemotherapy-related amenorrhea in premenopausal women with breast cancer[J]. Menopause， 2009， 16(1)：98-103.
13. Pérez-Fidalgo JA， Roselló S， García-Garré E， et al. Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients：the impact of addition of taxanes to anthracycline-based regimens[J]. Breast Cancer Res Treat， 2010， 120(1)：245-251.
14. Zhou WB， Yin H， Liu XA， et al. Incidence of chemotherapy-induced amenorrhea associated with epirubicin， docetaxel and navelbine in younger breast cancer patients[J]. BMC Cancer， 2010， 10：281.
15. Petrek JA， Naughton MJ， Case LD， et al. Incidence， time course， and determinants of menstrual bleeding after breast cancer treatment：a prospective study[J]. J Clin Oncol， 2006， 24(7)：1045-1051.
16. Swain SM， Land SR， Ritter MW， et al. Amenorrhea in premeno-pausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial[J]. Breast Cancer Res Treat， 2009， 113(2)：315-320.
17. Han HS， Ro J， Lee KS， et al. Analysis of chemotherapy-induced amenorrhea rates by three different anthracycline and taxane cont-aining regimens for early breast cancer[J]. Breast Cancer Res Treat， 2009， 115(2)：335-342.
18. Tham YL， Sexton K， Weiss H， et al. The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane[J]. Am J Clin Oncol，.
19. Plowchalk DR， Mattison DR.Reproductive toxicity of cyclophosphamide in the C57BL/6N mouse：1. Effects on ovarian structure and function[J]. Reprod Toxicol， 1992， 6(5)：411-421.
20. Demeestere I， Moffa F， Peccatori F， et al. Multiple approachesfor individualized fertility protective therapy in cancer patients[J]. Obstet Gynecol Int， 2012， 2012：961232.
21. Maltaris T， Weigel M， Mueller A， et al. Cancer and fertility preservation：fertility preservation in breast cancer patient[J]. Breast Cancer Res， 2008， 10(2)：206.
22. Meirow D， Lewis H， Nugent D， et al. Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide：clinical importance and proposed accurate investigative tool[J]. Hum Reprod， 1999， 14(7)：1903-1907.
23. Reh A， Oktem O， Oktay K. Impact of breast cancer chemotherapyon ovarian reserve：a prospective observational analysis by mens-trual history and ovarian reserve markers[J]. Fertil Steril， 2008，.
24. Sukumvanich P， Case LD， Van Zee K， et al. Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment：a prospective study[J]. Cancer， 2010， 116(13)：3102-3111.
25. Minisini AM， Menis J， Valent F， et al. Determinants of recovery from amenorrhea in premenopausal breast cancer patients receivingadjuvant chemotherapy in the taxane era[J]. Anticancer Drugs， 2009， 20(6)：503-507.
26. Zekri JM， El-Helw LM， Purohit OP， et al. Epirubicin/vinorelbine adjuvant chemotherapy in young women with breast cancer is associated with preservation of menstrual function[J]. Clin Oncol (R Coll Radiol)， 2008， 20(7)：513-516.
27. Miller JJ 3rd， Cole LJ. Changes in mouse ovaries after prolonged treatment with cyclophosphamide[J]. Proc Soc Exp Biol Med， 1970， 133(1)：190-193.
28. Koyama H， Wada T， Nishizawa Y， et al. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer[J]. Cancer， 1977， 39(4)：1403-1409.
29. Himelstein-Braw R， Peters H， Faber M. Morphological study of the ovaries of leukaemic children[J]. Br J Cancer， 1978， 38(1)：82-87.
30. Ataya KM， Valeriote FA， Ramahi-Ataya AJ. Effect of cyclophosphamide on the immature rat ovary[J]. Cancer Res， 1989， 49(7)：1660-1664.
31. Letterie GS. Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure[J]. Hum Reprod， 2004， 19(4)：831-837.
32. Takei H， Kurosumi M， Yoshida T， et al. Neoadjuvant endocrine therapy of breast cancer：which patients would benefit and what are the advantages?[J]. Breast Cancer， 2011， 18(2)：85-91.
33. Vanhuyse M， Fournier C， Bonneterre J. Chemotherapy-induced amenorrhea：influence on disease-free survival and overall survivalin receptor-positive premenopausal early breast cancer patients[J]. Ann Oncol， 2005， 16(8)：1283-1288.
34. (5)：1635-1639.
35. -317.
36. ， 30(2)：126-132.
37. ， 74(3)：175-192.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Influence Factors of Neoadjuvant Chemotherapy-Related Amenorrhea in Premenopausal Breast Cancer Women and Its Clinical Significance

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