Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk

Purpose We comprehensively evaluated genetic variants in DNA repair genes with premenopausal breast cancer risk. Methods In this nested case–control study of 239 prospectively ascertained premenopausal breast cancer cases and 477 matched controls within the Nurses’ Health Study II, we evaluated 1,463 genetic variants in 60 candidate genes across five DNA repair pathways, along with DNA polymerases, Fanconi Anemia complementation groups, and other related genes. Results Four variants were associated with breast cancer risk with a significance level of <0.01; two in the XPF gene and two in the XRCC3 gene. An increased risk was found in those harboring a greater number of missense putative risk alleles (a priori defined in an independent study) in the non-homologous end-joining (NHEJ) repair pathway of double-strand breaks (odds ratio (OR) per risk allele, 1.37 (95% confidence interval (CI), 1.03–1.82), P trend, 0.03). Conclusions This study implicates variants of genes in the double-strand break repair pathway in the etiology of premenopausal breast cancer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

绝经前激素受体阳性乳腺癌内分泌治疗现状

内分泌治疗是激素受体阳性乳腺癌患者术后辅助治疗的重要手段之一。在内分泌治疗的背景下,接受5年他莫昔芬治疗一直是绝经前患者的标准治疗方案。近年来,这一标准受到挑战。许多大型随机临床试验结果为绝经前患者辅助内分泌治疗提出了新的选择。本文拟将绝经前激素受体阳性乳腺癌患者的内分泌治疗现状做一综述。     

Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: Results from a controlled randomised trial

BackgroundAdjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial.Patients and methodsPremenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years.ResultsIn the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients <40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40–49 years of age or ?50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time.ConclusionIn this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women <40 years of age. The effect of tamoxifen was not significantly dependent on time.     

戈舍瑞林联合内分泌药物治疗绝经前晚期乳腺癌的临床研究

背景与目的:目前绝经前晚期乳腺癌的疗效仍不甚理想,卵巢去势是激素受体阳性晚期乳腺癌的有效治疗手段之一,卵巢去势药物促黄体激素释放激素类似物(luteinizing hormone-releasing hormone,LHRH),如戈舍瑞林,与手术或放疗去势疗效相当.本研究旨在探讨戈舍瑞林联合内分泌药物治疗激素受体阳性的绝经前晚期乳腺癌的疗效.方法:戈舍瑞林联合内分泌药物治疗组30例,个体匹配,选取同期30例应用三苯氧胺治疗的患者作为对照组,采用Kaplan-Meier法计算生存率,用log-rank方式进行差异的显著性检验,主要研究指标为无疾病再次进展生存时间(progression-free survival,PFS)和总生存时间(overall survival,OS).结果:治疗组和对照组的中位PFS分别为47.9个月和16.7个月,1,2和3年无疾病再次进展生存率分别为86.7% vs 58.9%,73.0% vs 43.1%和62.6% vs 38.3%(P=O.039);治疗组和对照组1、2和3年的总生存率分别为100% vs 83.3%、82.9% vs 57.5%和79.1% vs 48.9%(P=0.010).年龄＜40岁的患者,治疗组的PFS(P=O.027)和OS(P=0.007)较对照组显著提高,年龄≧40岁的患者使用戈舍瑞林则对预后无影响(P>O.05).疾病再次进展后继续使用戈舍瑞林中位生存时间较未使用者显著延长(28.2个月 vs 7.0个月),具有潜在受益(P=0.070).结论:对于激素受体阳性的绝经前晚期乳腺癌,戈舍瑞林联合内分泌药物可作为年龄＜40岁患者的标准内分泌治疗方法,对于出现疾病再次进展的患者,建议继续使用戈舍瑞林.     

Differences in breast cancer biological characteristics between ethnic groups in New Zealand

Objective To investigate differences in breast cancer biological characteristics between ethnic groups in Auckland, New Zealand. Design Prospective cohort study. Setting Auckland Breast Cancer Study Group. Participants All people diagnosed with breast cancer in the greater Auckland area between 2000 and 2005 who agreed to participate (1,577). Main outcome measures Size, grade, lymph node status, estrogen receptor (ER), progesterone receptor (PR), lymphovascular invasion (LVI), grade allowing for size, all compared with ethnicity. Results NZ Maori and Pacific Island participants had larger tumours (P < 0.0001), higher grade tumours (P < 0.0001) with more involved lymph nodes (P < 0.0001). When allowing for size, there was still an indication that NZ Maori people had higher grade tumours (P = 0.03). There was no difference in ER, PR and LVI between ethnic groups. Conclusion These data suggest differences in tumour biology related to ethnicity in the Auckland population and this has implications for breast cancer screening and management.     

Reproductive factors and breast cancer risk among older women

Reproductive factors have been shown to affect pre- and postmenopausal breast cancer risk differently, but whether there are additional age-specific differences among menopausal women as they age has not been clarified. We analyzed data from a large population-based case–control study that included 1,508 breast cancer cases and 1,556 controls, aged 20–98 years, who completed an in-home interviewer-administered questionnaire. The following subgroups were created to examine if the associations between reproductive factors and breast cancer risk varied by age- and menopausal-status: premenopausal (n = 968), postmenopausal <65 years (n = 1,045), postmenopausal ≥65 years (n = 958). Among postmenopausal women ≥65 years, ever having breastfed decreased risk (odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.48, 0.92), and a strong dose–response relationship was observed for longer durations of breastfeeding (P trend = 0.02), with the most pronounced protective effect observed for ≥14 months of breastfeeding (OR = 0.40, 95% CI = 0.21,0.76). Late age at first birth (AFB) and older age at last birth (ALB) were associated with non-statistically significant increases in breast cancer risk in this older group, while late age at menarche and surgical menopause decreased risk. ORs for multiparity were close to the null. Among premenopausal women and postmenopausal women <65 years, multiparity significantly decreased risk, and older AFB nonsignificantly increased risk. Our findings suggest that the well-known protective effect of multiparity attenuates with older age. Moreover, breastfeeding, one of the few potentially modifiable risk factors for breast cancer, was an important factor in decreasing risk among older parous postmenopausal women.     

Investigation of menstruation recovery after LH-RH agonist therapy for premenopausal patients with breast cancer

BACKGROUND: Recently Luteinizing hormone-releasing hormone (LH-RH) agonist has been used for premenopausal patients with breast cancer as endocrine therapy. However, there is no consensus regarding recovery of menstruation after long-term treatment with LH-RH agonist. We investigated recovery of menstruation after this treatment. METHODS: We investigated 28 premenopausal patients with breast cancer who underwent operation at Chiba Cancer Center Hospital in 1995 or 1996. The patients were treated with LH-RH agonist (goserelin) for 24 months as an adjuvant therapy, and were observed for more than 6 months after the last goserelin depot. Ages ranged 31-55 years old from at the time of last treatment. We defined recovery of menstruation as regular menstruation occurring more than three times. RESULTS: There were 22 patients in the recovery group (range: 31-53 years, mean 45.1 years). There were 6 patients in the non-recovery group (range: 50-55 years, mean 52.2 years). The overall recovery rate was 78.6%. Recovery rate was 81.8% for the patients under 50 years, and 66.7% for over 51 years. We separated all patients into groups by age at 5 years intervals, and investigated the distribution of the recovery time. In the recovery group (22 patients), there were 15 patients (68.2%) who confirmed recovery of menstruation within 6 months. CONCLUSION: Our investigation suggested that the recovery of menstruation after this therapy would occur in those less than 50 years old, within 6 months from the last treatment.     

Vascular endothelial growth factor and breast cancer risk

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and is important to carcinogenesis. Previous studies relating circulating levels of VEGF to breast cancer have been limited by small numbers of participants and lack of adjustment for confounders. We studied the association between serum VEGF and breast cancer in an unmatched case–control study of 407 pre- and postmenopausal women (n = 203 cases, n = 204 controls). Logistic regression was used to model the breast cancer risk as a function of natural log transformed VEGF levels adjusted for age, Gail score, education, physical activity, history of breastfeeding, serum testosterone, and hormone therapy (HT) use. The majority of the population was postmenopausal (67.6%) and the average age was 56 years; age and menopausal status were similar among cases and controls. Geometric mean VEGF levels were non-significantly higher in cases (321.4 pg/ml) than controls (291.4 pg/ml; p = 0.21). In a multivariable model, the odds of breast cancer was 37% higher for women with VEGF levels ≥314.2 pg/ml compared to those with levels below 314.2 pg/ml, albeit not significantly (p = 0.16). There was no interaction between VEGF and menopausal status (p = 0.52). In this case–control study, VEGF was not significantly associated with breast cancer risk in pre- and postmenopausal women.     

Breast cancer risk and hysterectomy status: the Multiethnic Cohort study

Objective  The main objective was to examine the association between simple hysterectomy (without bilateral oophorectomy) and breast cancer risk. Because hysterectomy prevalence varies by ethnicity, the secondary objective was to examine whether inclusion of women with hysterectomies affects the estimates of breast cancer risk by ethnicity. Methods  The Multiethnic Cohort study was assembled between 1993 and 1996 and included 68,065 women from Hawaii and Los Angeles, aged 45–75 years, without any missing information or bilateral oophorectomy. Hysterectomy status was self-reported. After 7.7 years median follow-up, 1,862 cases of invasive breast cancer were identified. Proportional hazards models were used to estimate relative risks (RR) while controlling for known risk factors. Results  Prevalence of simple hysterectomy varied from 12% to 29% among the ethnic groups (White, African American, Native Hawaiian, Japanese American, and Latina). Overall, hysterectomy was not associated with breast cancer risk (RR = 0.98). Although the RRs were nonsignificantly elevated by 15% in White women and nonsignificantly reduced by 15% in Latinas of non-US origin, the variation by ethnicity was not significant (p _interaction = 0.48). The breast cancer risk associated with ethnicity was very similar when estimated with and without women with hysterectomies. Conclusions  This study suggests that simple hysterectomy status does not alter breast cancer risk. Therefore, inclusion of women with simple hysterectomies does not substantially change estimated risk of breast cancer by ethnicity.     

Population-based estimates of the relation between breast cancer risk,tumor subtype,and family history

Objective Many studies that have estimated the breast cancer risk attributable to family history have been based on data collected within family units. Use of this study design has likely overestimated risks for the general population. We provide population-based estimates of breast cancer risk and different tumor subtypes in relation to the degree, number, and age at diagnosis of affected relatives. Methods Cox Proportional Hazards to calculate risks (hazard ratios; 95% confidence interval) of breast cancer and tumor subtypes for women with a family history of breast cancer relative to women without a family history among a cohort of 75,189 women age ≥40 years of whom 1,087 were diagnosed with breast cancer from June 1, 2001–December 31, 2005 (median follow-up 3.16 years). Results Breast cancer risk was highest for women with a first-degree family history (1.54; 1.34–1.77); and did not differ substantially by the affected relative’s age at diagnosis or by number of affected first-degree relatives. A second-degree family history only was not associated with a significantly increased breast cancer risk (1.15; 0.98–1.35). There was a suggestion that a positive family history was associated with risk of triple positive (Estrogen+/Progesterone+/HER2+) and HER2-overexpressing tumors. Conclusions While a family history of breast cancer in first-degree relatives is an important risk factor for breast cancer, gathering information such as the age at diagnosis of affected relatives or information on second-degree relative history may be unnecessary in assessing personal breast cancer risk among women age ≥40 years.     

Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies

BackgroundBreast cancer is composed of distinct subtypes defined mainly based on the expression of hormone receptors (HR) and HER2. For years, reproductive factors were shown to impact breast cancer risk but it is unclear whether this differs according to tumor subtype. In this meta-analysis we evaluated the association between parity, age at first birth, breastfeeding and the risk of developing breast cancer according to tumor subtype.MethodsPubMed and Embase were searched to identify epidemiological studies that evaluated the impact of parity and/or age at first birth and/or breastfeeding on breast cancer risk with available information on HR and HER2. Tumor subtypes were defined as: luminal (HR-positive, HER2-negative or HER2-positive), HER2 (HR-negative, HER2-positive) and triple-negative (HR-negative, HER2-negative). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. The MOOSE guidelines were applied.ResultsThis meta-analysis evaluated 15 studies, including 21,941 breast cancer patients and 864,177 controls. Parity was associated with a 25% reduced risk of developing luminal subtype (pOR 0.75; 95% CI, 0.70–0.81; p < 0.0001). Advanced age at first birth was associated with an increased risk of developing luminal subtype (pOR 1.15; 95% CI, 1.00–1.32; p = 0.05). Ever breastfeeding was associated with a reduced risk of developing both luminal (pOR 0.77; 95% CI, 0.66–0.88; p = 0.003) and triple-negative (pOR 0.79, 95% CI, 0.66–0.94; p = 0.01) subtypes.ConclusionsThe reproductive behaviors impact the risk of developing breast cancer but this varies according to subtype.     

Parity in relation to survival following breast cancer

Aim

The present study examines the association between parity and survival following breast cancer diagnosis.

Methods

Medical records of 4453 women diagnosed with breast cancer in Malmö, Sweden, between 1961 and 1991 were analysed. All women were followed until 31 December 2003, using the Swedish Cause-of-Death Registry. Breast cancer specific mortality rate was calculated in different levels of parity. Corresponding relative risks, with 95% confidence intervals (CI), were obtained using Cox's proportional hazards analysis. All analyses were adjusted for potential prognostic factors and stratified for age, menopausal status and diagnostic period.

Results

As compared to women with one child, nulliparity (RR 1.27: 95% CI 1.09–1.47), and high parity (four or more children) (1.49: 1.20–1.85) were positively associated with a high mortality from breast cancer. When adjusted for potential confounders, the association was only statistically significant for high parity (1.33: 1.07–1.66). In the analyses stratified on age and menopausal status, there was a similar positive association between high parity and breast cancer death in all strata, although only statistically significant among women older than 45 years of age or postmenopausal. Nulliparity was associated with breast cancer death in women that were younger than 45 years of age (1.28: 0.79–2.09) or premenopausal (1.30: 0.95–1.80), but these associations did not reach statistical significance. There was no association between nulliparity and breast cancer death in women older than 45 years of age or postmenopausal. All associations were similar in analyses stratified for diagnostic period.

Conclusion

Women with four or more children have a poor breast cancer survival as compared to women with one child.     

Survival after bilateral breast cancer: results from a population-based study

Background Controversy exists on the impact of bilaterality of breast cancer on survival. We used population-based data to compare survival of women with unilateral versus bilateral breast cancer. Patients and methods At the Geneva cancer registry, we identified all 7,912 women diagnosed with invasive breast cancer between 1970 and 2002. Breast cancers were categorized as unilateral, synchronous bilateral (contralateral tumour diagnosed within six months after the first tumour) and metachronous bilateral (contralateral tumour diagnosed over six months after the first tumour). With multivariate modelling we compared characteristics and survival between women with unilateral and bilateral disease. Results Patients with synchronous bilateral tumours (n = 155, 2.0%) had more often lobular histology and less frequently stage I disease than women with unilateral disease. Women with metachronous breast cancer (n = 219, 2.8%) received less often chemotherapy or hormone therapy for their first tumours. Ten-year disease-specific survival was similar (66%) after unilateral and metachronous bilateral breast cancer, but worse after synchronous bilateral cancer (51%). After adjustment, breast cancer mortality risks were not significantly increased for women with either synchronous or metachronous bilateral disease (Hazard ratios 1.1 (0.8–1.5) and 0.8 (0.5–1.4), respectively). Conclusion This large population-based study indicates that bilaterality of breast cancer is not associated with impaired survival.     

Comparison of cancer registry and clinical data as predictors for breast cancer survival

Background  In spite of the increasing amount of clinically relevant information for survival from breast cancer, the amount of data recorded in a population-based cancer registry is limited and the registry-based survival predictions are routinely made without clinical details. Objective  To find out how important is the role of screening and clinical tumor characteristics in addition to cancer registry information in describing the breast cancer survival. Methods  A representative clinical database on 483 breast cancer patients diagnosed during 1996–1997 in Tampere University Hospital Area was linked with Finnish Cancer Registry data and a survival model including the available registry variables was compared to models including screen-detection information and clinical tumor characteristics also. Results and conclusion  Estimates of registry stage and age act as surrogates for clinical variables and mammography-detection. The surrogacy was found to be almost complete indicating that clinical variables are not necessarily needed when making breast cancer mortality predictions based on a population-based cancer registry. In cases with dissimilar staging cancer registry stage gave a better picture of the breast cancer survival than the clinical stage. This work was performed in Finnish Cancer Registry, Helsinki, Finland.     

Cyclical mastopathy and premenopausal breast cancer risk

Cyclical mastopathy (CM) is a common clinical syndrome of premenstrual breast swelling and tenderness. Its symptoms are relieved by reduction in dietary fat intake and, because fat intake may be associated with breast cancer risk, it was hypothesized that CM may also be related to breast cancer risk.This case-control study included 192 premenopausal women with a recent history of axillary node-negative breast cancer and 192 age-matched premenopausal controls. Subjects provided information on diet and risk factors, and they recorded breast symptoms prospectively during one menstrual cycle. Symptoms in the non-cancerous breast of cases and the matched (right or left) breast of controls were examined.A cyclical pattern of symptoms was identified in both groups; breast tenderness scores were similar post-menstrually (p = 0.31) but were significantly higher premenstrually in the case group (p = 0.03). Cases also had a greater premenstrual increase in breast tenderness than controls (p = 0.03). When the effects of other risk factors for breast cancer were included in multivariate analyses, the association of cyclical tenderness with breast cancer persisted (p = 0.05), the odds ratio for severe tenderness being 3.32.Thus, we have identified an association of cyclical breast tenderness with breast cancer risk in premenopausal women. The association persists after consideration of diet and the effects of other breast cancer risk factors.     

Insulin and related factors in premenopausal breast cancer risk

Background: Insulin and insulin-like growth factor I (IGF-I) are important mitogens in vitro and in vivo. It has been hypothesized that these factors may play an important role in the development of breast cancer. Methods: A case-control study comparing plasma insulin levels in 99 premenopausal women with newly diagnosed node-negative invasive carcinoma of the breast and 99 age-matched controls with incident biopsied non-proliferative breast disease (NP) was conducted. Women with known diabetes were excluded. Results: For the entire study group, mean age was 42.6 ± 5.1 years and mean weight was 62.9 ± 10.3 kg. After adjustment for age and weight, elevated insulin levels were significantly associated with breast cancer, Odds Ratio (OR) for women in the highest insulin quintile versus the lowest quintile=2.83 (95% Confidence Interval [CI] 1.22–6.58). There were no statistically significant differences between cases and controls for IGF-I and IGFBP-1 levels. However, after adjustment for age, the association between plasma levels of insulin-like growth factor binding protein 3 (IGFBP-3) and breast cancer approached statistical significance; OR for highest quintile versus lowest quintile of IGFBP-3 being 2.05 (95% CI, 0.93–4.53). All results were independent of diet and other known risk factors for breast cancer. Conclusion: Circulating insulin levels and possibly IGFBP-3 levels are elevated in women with premenopausal breast cancer. This association may reflect an underlying syndrome of insulin resistance that is independent of obesity.     

The reproductive function and the risk of developing cancer of the breast in different ethnic groups

The study was concerned with the relationship between certain characteristics of reproductive case history and risk for breast cancer development in three different ethnic groups of females living in the Moldavian SSR: Moldavians, Ukrainians and Russians. Risk of cancer was found to be higher in all groups in cases of premenstrual syndrome, late onset of sexual life (greater than or equal to 26 years), suspension of sexual life for more than 12 months, late first pregnancy and delivery, low productivity (0-1 birth in case history), agalactia, and menstrual cycle resumption 1-2 months after childbirth. However, certain ethnic differences in relationships between such factors as age of menopause onset, no pregnancies, late pregnancy (greater than or equal to 40 years) and type of contraceptives used and risk of cancer are rather due to the difference in prevalence of said factors in the groups under study. The results of the investigation suggest a common pattern of influence of reproductive case history factors on risk for breast cancer in different ethnic groups.     

Ethnic and geographic differences in mammographic density and their association with breast cancer incidence

The objective of this pooled analysis was to compare differences in dense areas and percent mammographic densities to breast cancer incidence in populations at different breast cancer risk. The data set included 1,327 women aged 40–80: Caucasians from Norway, Arizona, and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. One reader performed computer-assisted quantitative density assessment for all mammographic films. Multiple linear regression models evaluated the influence of the covariates on breast density. Spearman correlation coefficients (r _s) estimated the association between breast density and breast cancer incidence for the seven populations. After adjustment for covariates, ethnicity, but not location, was significantly associated with breast density. In the full model, 19% of the variation in the dense areas and 46% in the variation of percent densities were explained by measured risk factors. Native Hawaiians had the largest dense areas and women in Japan the smallest, whereas percent densities were highest among Native Hawaiians and Japanese in Hawaii and lowest among Norwegian women. The mean age-adjusted dense area had the strongest association with breast cancer incidence (r _s = 0.93, P = 0.003); the relation with percent density was considerably weaker (r _s = 0.32, P = 0.48). The correlation between age-adjusted dense area and breast cancer incidence remained strong after selectively removing individual data points. This comparison of mammographic densities suggests that, on a group level, age-adjusted dense areas may reflect breast cancer incidence better than percent densities.     

BRCA1 and BRCA2 status in a Central Sudanese series of breast cancer patients: interactions with genetic, ethnic and reproductive factors

The etiology of breast cancer in Africa is scarcely investigated. Breast cancer was responsible for 456/2,233 cancer patients (20.4%) ascertained between 1999 and 2004 at Gezira University, Central Sudan. Male breast cancer accounted for 16/456 patients (3.5%), 275/440 female patients (62.5%) were premenopausal and 150/440 cases (34%) occurred in women with > or =5 childbirths. We characterized for germline BRCA1/2 mutations a one-year series of patients (34 females, 1 male) selected by diagnosis within age 40 years or male gender. Overall 33/35 patients were found to carry 60 BRCA1/2 variants, of which 17 (28%) were novel, 22 (37%) reported in populations from various geographic areas and 21 (35%) reported worldwide. Detected variants included 5 truncating mutations, one of which (in BRCA2) was in the male patient. The 55 non-truncating variants included 3 unclassified variants predicted to affect protein product and not co-occurring with a truncating mutation in the same gene. Patients were from different tribes but AMOVA showed that most BRCA1/2 variation was within individuals (86.41%) and patients clustered independently of tribe in a phylogenetic tree. Cluster analysis based on age at cancer diagnosis and reproductive variables split female patients in two clusters that, by factor analysis, were explained by low versus high scores of the total period occupied by pregnancies and lactation. The cluster with low scores comprised all 4 patients with truncating mutations and 3 of the 4 carriers of unclassified variants predicted to affect protein product. Our findings suggest that in Central Sudan BRCA1/2 represent an important etiological factor of breast cancer in males and young women less exposed to pregnancy and lactation. Factors other than BRCA1/2 may contribute to breast cancer in young highly multiparous women who breast-fed for prolonged periods.     

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。