绝经前乳腺癌化疗致闭经的观察及临床意义

目的观察术后辅助化疗对绝经前乳腺癌患者月经状态的影响,探讨化疗致闭经（CIA）的影响因素及其与预后的关系。方法绝经前乳腺癌患者160例均行术后辅助化疗,随访至化疗后12～72个月,记录月经状态、复发和生存情况。分别检测16例无CIA患者化疗后、17例CIA恢复患者和17例CIA未恢复患者闭经后促卵泡激素（FSH）和雌二醇（E2）水平,同时检测16例乳腺癌绝经患者的激素水平作为对照。结果有107例（66．9％）患者出现CIA,其中24例（22．4％）恢复,83例（77．6％）未恢复。CIA的发生、恢复均与患者的年龄有关（P〈0．01）。应用不同化疗方案化疗CIA的发生率不同,由高到低依次是FEC方案（70．1％）、含紫杉类方案（69．2％）和CMF方案（45.2％）。Cox多因素分析结果显示,CIA是乳腺癌复发有意义的影响因素。激素受体阳性患者中,无CIA患者无病生存率为80．0％,CIA患者为90．1％,差异有统计学意义（P=0．04）。无CIA患者、CIA恢复患者、CIA未恢复患者、乳腺癌绝经患者间FSH和E2差异有统计学意义（P值分别为0．001和0．026）。结论化疗造成卵巢功能损害,可致绝经前乳腺癌患者发生CIA。对激素受体阳性的患者,CIA的发生可改善预后。

Observation and clinical significance of adjuvant chemotherapy-induced amenorrhea in premenopausal breast cancer patients

OBJECTIVE: A retrospective analysis of 160 pre-menopausal breast cancer patients was carried out to elucidate the the menstrual outcome in those cases who had undergone adjuvant chemotherapy after surgery, and evaluate the relationship between chemotherapy-induced amenorrhea (CIA) and recurrence of the disease. METHODS: 160 pre-menopausal breast cancer patients were collected, 62/159 (39.0%) of them were node positive, 91/158 (57.6%) were ER positive, and 95/155 (61.3%) were PR positive. 111 cases had infiltrative ductal carcinoma, 26 cases had infiltrative lobular carcinoma, and 22 cases with others. In 152 cases data were collected by face-to-face interview and 8 cases by phone conversation. Types and cycles of chemotherapy regimen as well as menstrual abnormalities were recorded before, during, and after chemotherapy completion. Follow up duration was 12-72 months after chemotherapy completion for all patients. RESULTS: 107 (66.9%) developed CIA, 24 cases returned to normal menses (22.4%), 83 cases continued CIA during more than 12-month follow up (77.6%). The rate of CIA increased with age (P < 0.01). During the follow up, disease free survival (DFS) rate was 85.9% in CIA group and 79.2% in non-CIA group, with no statistically significant difference. But in hormonal receptor positive patients, DFS was 80.0% in non-CIA and 90.1% in CIA, respectively (P = 0.04), showing a significant difference. Because of the small number of died cases, no analysis of the overall outcome was carried out. CONCLUSION: Adjuvant chemotherapy causes ovarian function suppression, and may further leading to amenorrhoea. Women who experienced amenorrhoea after chemotherapy had a significantly better disease-free survival (DFS) rate showed by univariate analysis than women who continued normal menstruation. Chemotherapy is insufficient therapy for very young patients who are in high risk with hormone responsive disease, particularly when chemotherapy fails to induce amenorrhea. Further research is needed to evaluate interventional chemotherapy to improve the quality of life in women with early stage breast cancer who experienced ovarian toxicity. The post-chemotherapy menstruation status is a clinically valuable, objective and salient marker for sufficient endocrine effect of chemotherapy in ER/PR-positive premenopausal patients.