• 四川大學(xué)華西醫(yī)院甲狀腺乳腺外科（四川成都 610041）;

目的 　分析絕經(jīng)前乳腺癌患者接受新輔助化療后閉經(jīng)的相關(guān)影響因素，了解新輔助化療相關(guān)的閉經(jīng)（NCRA）與新輔助化療后腫瘤降期的關(guān)系。
方法 　回顧性隨訪觀察我院2006年3月至2011年3月期間224例絕經(jīng)前乳腺癌患者接受新輔助化療后月經(jīng)狀態(tài)的改變及新輔助化療后彩超下乳房腫瘤的變化情況，分析新輔助化療時患者年齡、化療方案、腫瘤病理組織學(xué)特征（ER/PR和Her-2）、術(shù)后服用他莫昔芬（tamoxifen，TAM）與NCRA及其隨后月經(jīng)恢復(fù)的關(guān)系，以及新輔助化療后腫瘤的變化與NCRA的關(guān)系。
結(jié)果 　224例患者中有166例（74.11%）患者出現(xiàn)NCRA，其中有15例停經(jīng)但雌激素水平增高而行卵巢切除或接受戈舍瑞林治療，余151例NCRA患者中有40例（26.49%）出現(xiàn)月經(jīng)恢復(fù)。單因素及多因素分析結(jié)果顯示，NCRA的發(fā)生及隨后的月經(jīng)恢復(fù)均與患者的年齡有關(guān)（P＜0.001，P=0.001）；不同化療方案對NCRA的發(fā)生無明顯影響（P＞0.05），但是對NCRA后月經(jīng)恢復(fù)有重要影響（P＜0.001）；腫瘤的ER/PR和Her-2表達(dá)和是否服用TAM對NCRA發(fā)生及其隨后的月經(jīng)恢復(fù)均無明顯影響（P＞0.05）。發(fā)生NCRA時的化療周期數(shù)隨患者年齡的增長而減少，與NCRA后月經(jīng)的恢復(fù)無關(guān)（P＞0.05）。NCRA的發(fā)生與新輔助化療后腫瘤的降期無關(guān)（P＞0.05）。
結(jié)論 　大多數(shù)絕經(jīng)前乳腺癌患者接受新輔助化療后會出現(xiàn)閉經(jīng)，年齡越大的患者越容易發(fā)生NCRA，而且發(fā)生NCRA時接受化療的周期數(shù)更少；年齡和化療方案都會影響NCRA后月經(jīng)的恢復(fù)；NCRA的發(fā)生未影響新輔助化療的近期療效。

引用本文： 范雪嬌,王榮,陳潔,田春祥,曾荷淋,呂青. 絕經(jīng)前乳腺癌患者新輔助化療相關(guān)閉經(jīng)的影響因素及臨床意義探討. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(8): 856-861. doi: 復(fù)制

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.
  1. 1. Beasley GM， Olson JA Jr. What’s new in neoadjuvant therapy for breast cancer?[J]. Adv Surg， 2010， 44：199-228.
  2. 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. 3. Ena G. Neoadjuvant therapy in breast cancer[J]. Rev Med Brux， 2011， 32(4)：243-246.
  4. 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. 5. Sapunar F， Smith IE. Neoadjuvant chemotherapy for breast cancer[J]. Ann Med， 2000， 32(1)：43-50.
  6. 6. Anchan RM， Ginsburg ES. Fertility concerns and preservation in younger women with breast cancer[J]. Crit Rev Oncol Hematol，.
  7. 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. 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. 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. 10. Hulvat MC， Jeruss JS. Maintaining fertility in young women with breast cancer[J]. Curr Treat Options Oncol， 2009， 10(5-6)：.
  11. 11. Oktem O， Oktay K. Fertility preservation for breast cancer patients[J]. Semin Reprod Med， 2009， 27(6)：486-492.
  12. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 31. Letterie GS. Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure[J]. Hum Reprod， 2004， 19(4)：831-837.
  32. 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. 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. 34. (5)：1635-1639.
  35. 35. -317.
  36. 36. ， 30(2)：126-132.
  37. 37. ， 74(3)：175-192.