35岁以下三阴性乳腺癌临床病理特征及预后分析
|
摘要
目的分析影响35岁以下三阴性乳腺癌患者的预后因素。方法回顾性分析来自山西省肿瘤医院、山西医科大学第一附属医院、海南省人民医院确诊于2002—2016年,确诊年龄≤35岁的女性三阴性乳腺癌患者临床资料,排除既往恶性肿瘤病史且临床资料及随访记录不全的患者,共105例患者纳入研究,其中确诊年龄≤25者19例,26～35岁者86例。由临床病历及门诊随访、电话访问获得患者的信息。使用Kaplan-Meier法计算无病生存率(DFS)及总生存率(OS),Cox比例风险模型评估风险比(hazard ratio,HR)及其相关的95%置信区间(95%confidential interval,95%CI)。结果确诊年龄≤25岁与26～35岁患者在临床病理学特征及治疗方式的选择上差异均无统计学意义(P>0.05),生存分析结果显示两者的DFS、OS比较差异亦无统计学意义(P>0.05);选择不同术式的患者间DFS、OS比较差异均无统计学意义(P>0.05);初潮年龄≤12岁的患者DFS及OS明显低于初潮年龄>12岁的患者,差异均有统计学意义(P<0.05);多因素分析结果显示,初潮年龄(HR 0.697 4,95%CI 0.563 4～0.863 1)、妊娠相关性(HR 2.673 9,95%CI 1.158 1～6.174 1)、淋巴结阳性(HR 4.915 4,95%CI 2.377 4～10.162 7)是影响患者DFS的独立预后因素;影响OS的独立预后因素为初潮年龄(HR 0.598 8,95%CI 0.462 6～0.775)、淋巴结阳性(HR 7.751 9,95%CI 2.923 0～20.559)。结论≤25岁与26～35岁的女性三阴性乳腺癌患者在临床病理学特征及预后上无差异,初潮年龄、妊娠相关性及淋巴结阳性是影响患者预后的独立因素。应当进一步探究生殖因素与年轻三阴性乳腺癌患者间的预后关系。
Objective To compare the clinicopathological features and prognosis of very young women(<35 years) with triple-negative breast cancer, and to analyze the prognostic factors of very young women(<35 years) with triple-negative breast cancer. Methods The clinical data of 105 very young women(<35 years) with triple-negative breast cancer, excluding patients with previous malignancies and incomplete clinical data and follow-up records, from Shanxi Provincial Cancer Hospital, First hospital of Shanxi Medical University, Hainan General Hospital between 2002 and 2016 were retrospectively analyzed. Among of the patients, 19 patients were diagnosed with age ≤25 years and 86 patients between 26 and 35 years old. The clinical data included the clinical medical records and personal interview. The disease-free survival(DFS) and overall survival(OS) were calculated by Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis. Results There were no significant differences in the clinicopathological features and treatment options between the patients diagnosed of age ≤25 years and 26～35 years old(P>0.05).Survival analysis showed there was no significant difference between the two age groups in DFS and OS(P>0.05). Subgroup analysis found that there was no significant difference in the DFS and OS between patients with different surgical method, and the same trend was observed in both the two age groups(P>0.05). DFS and OS in patients with menarche age ≤12 years were significantly lower than those with menarche age >12 years(P<0.05). Multivariate analysis showed that menarche age(HR 0.697 4, 95% CI 0.563 4-0.863 1), pregnancy-related(HR 2.673 9, 95% CI 1.158 1-6.174 1),and lymph node positive >3(HR 4.915 4, 95 % CI 2.377 4-10.162 7) were independent prognostic factors for DFS in patients; and independent prognostic factors affecting OS: age at menarche(HR 0.5988, 95% CI 0.462 6-0.775), pregnancy-related(HR 2.305 2, 95% CI 0.973 9-5.456), lymph node-positive(HR 7.751 9), 95% CI 2.923 0-20.559).Conclusions There are no differences in clinicopathological features and prognosis between women with triple-negative breast cancers aged ≤25 years and 26 years old to 35 years old. The age of menarche, pregnancy-related, and lymph node positive are independent factors affecting the prognosis of patients. The prognostic relationship between reproductive factors and young triple-negative breast cancer patients should be further explored.
Objective To compare the clinicopathological features and prognosis of very young women(<35 years) with triple-negative breast cancer, and to analyze the prognostic factors of very young women(<35 years) with triple-negative breast cancer. Methods The clinical data of 105 very young women(<35 years) with triple-negative breast cancer, excluding patients with previous malignancies and incomplete clinical data and follow-up records, from Shanxi Provincial Cancer Hospital, First hospital of Shanxi Medical University, Hainan General Hospital between 2002 and 2016 were retrospectively analyzed. Among of the patients, 19 patients were diagnosed with age ≤25 years and 86 patients between 26 and 35 years old. The clinical data included the clinical medical records and personal interview. The disease-free survival(DFS) and overall survival(OS) were calculated by Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis. Results There were no significant differences in the clinicopathological features and treatment options between the patients diagnosed of age ≤25 years and 26～35 years old(P>0.05).Survival analysis showed there was no significant difference between the two age groups in DFS and OS(P>0.05). Subgroup analysis found that there was no significant difference in the DFS and OS between patients with different surgical method, and the same trend was observed in both the two age groups(P>0.05). DFS and OS in patients with menarche age ≤12 years were significantly lower than those with menarche age >12 years(P<0.05). Multivariate analysis showed that menarche age(HR 0.697 4, 95% CI 0.563 4-0.863 1), pregnancy-related(HR 2.673 9, 95% CI 1.158 1-6.174 1),and lymph node positive >3(HR 4.915 4, 95 % CI 2.377 4-10.162 7) were independent prognostic factors for DFS in patients; and independent prognostic factors affecting OS: age at menarche(HR 0.5988, 95% CI 0.462 6-0.775), pregnancy-related(HR 2.305 2, 95% CI 0.973 9-5.456), lymph node-positive(HR 7.751 9), 95% CI 2.923 0-20.559).Conclusions There are no differences in clinicopathological features and prognosis between women with triple-negative breast cancers aged ≤25 years and 26 years old to 35 years old. The age of menarche, pregnancy-related, and lymph node positive are independent factors affecting the prognosis of patients. The prognostic relationship between reproductive factors and young triple-negative breast cancer patients should be further explored.
引文
[1] HOWLADER N, ALTEKRUSE SF, LI CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2status[J]. J Natl Cancer Inst, 2014, 106(5):dju055.
[2] MOINFAR F. Is‘basal-like’carcinoma of the breast a distinct clinicopathological entity? A critical review with cautionary notes[J].Pathobiology, 2008, 75(2):119-131.
[3] BLEYER A, VINY A, BARR R. Cancer in 15-to 29-year-olds by primary site[J]. Oncologist, 2006, 11(6)590-601.
[4] LIU Y, XIN T, HUANG DY, et al. Prognosis in very young women with triple-negative breast cancer:retrospective study of 216 cases[J]. Med Oncol, 2014, 31(12):222.
[5] RHEE J, HAN SW, OH DY, et al. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer[J]. BMC Cancer, 2008, 8:307.
[6] AMIN MB, EDGE S, GREENE F, et al(eds). AJCC cancer staging manual, 8thEd[S]. Chicago, IL:Springer, 2017:589-636.
[7] LIEDTKE C, KENNETH HR, THOMAS K, et al. The prognostic impact of age in patients with triple-negative breast cancer[J]. Breast Cancer Research and Treatment, 2013, 138(2):591-599.
[8] SALMAN O, ALOK KD, ANTHONY LN, et al. Prognostic impact of age at diagnosis in triple negative breast cancer:Analysis of 204patients from single institution registry[J]. Journal of Clinical Oncology, 2018, 36(15):e13130.
[9] VERONESI U, CASCINELLI J, MARIANI L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radicalmastectomy for early breast cancer[J]. N Engl J Med,2002, 347(16):1227-1232.
[10] FISHER B, ANDERSON S, BRYANT J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer[J]. N Engl J Med, 2002, 347(16):1233-1241.
[11]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2017年版)[J].中国癌症杂志, 2017, 27(9):695-760.
[12] RAKHA EA, EL-SAYED ME, GREEN AR, et al. Prognostic markers in triple-negative breast cancer[J]. Cancer, 2007, 109(1):25-32.
[13] YUAN ZY, WANG SS, GAO Y, et al. Clinical characteristics and prognosis of triple-negative breast cancer:a report of 305 cases[J].Ai Zheng, 2008, 27(6):561-565.
[14] KWON J, EOM KY, KOO TR, et al. A prognostic model for patients with triple-negative breast cancer:importance of the modified nottingham prognostic index and age[J]. J Breast Cancer, 2017, 20(1):65-73.
[15] CANCELLO G, MAISONNEUVE P, MAZZA M,et al. Pathological features and survival outcomes of very young patients with early breast cancer:how much is"very young"?[J]. Breast, 2013, 22(6):1046-1051.
[16]李云,穆兰,阮玉霞,等.乳腺癌分子分型对保乳手术安全性的影响[J].中华肿瘤杂志, 2018, 40(5):341-346.
[17] ADKINS FC, GONZALEZ-ANGULO AM, LEI X, et al. Triple-negative breast cancer is not a contraindication for breast conservation[J].Ann Surg Oncol, 2011, 18(11):3164-3173.
[18] RADOSA JC, EATON A, STEMPEL M, et al. Evaluation of local and distant recurrence patterns in patients with triple-negative breast cancer according to age[J]. Ann Surg Oncol, 2017, 24(3):698-704.
[19] PILEWSKIE M, GORODINSKY P, FOUGHT A,et al. Association between recency of last pregnancy and biologic subtype of breast cancer[J]. Ann Surg Oncol, 2012, 19(4):1167-1173.
[20] BLADSTR?M A, ANDERSON H, OLSSON H. Worse survival in breast cancer among women with recent childbirth:results from a Swedish population-based register study[J]. Clin Breast Cancer,2003, 4(4):280-285.
[21] JOHANSSON ALV, ANDERSSON TML, HSIEH CC, et al. Tumor characteristics and prognosis in women with pregnancy-associated breast cancer[J]. Int J Cancer, 2018, 142(7):1343-1354.
[22] AZIM HA, SANTORO L, RUSSELL EW, et al. Prognosis of pregnancy-associated breast cancer:a meta-analysis of 30 studies[J].Cancer Treat Rev, 2012, 38(7):834-842.
[23] NAN S, JI YC, HYUNA S, et al. Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival[J].PLoS One, 2015, 10(4):e0123994.
[24] DANA CZ,FELICIA C,RAMONA S, et al. Relationship between reproductive risk factors, tumor characteristics and survival in breast cancer molecular groups[J]. Journal of Advances in Biology, 2016, 8(3):1646-1654.
[25] LUO HJ, LUO P, YANG GL et al. G-protein coupled estrogen receptor 1 expression in primary breast cancers and its correlation with clinicopathological variables[J]. J Breast Cancer, 2011, 14(3):185-190.
[26] YU T, LIU M, LUO H, et al. GPER mediates enhanced cell viability and motility via non-genomic signaling induced by 17β-estradiol in triple-negative breast cancer cells[J]. J Steroid Biochem Mol Biol,2014, 143:392-403.
[27] VIHKO R, APTER D. Endocrine characteristics of adolescent menstrual cycles:impact of early menarche[J]. Steroid Biochem, 1984,20(1):231-236.
[28] LIU LIANG-CHIH,SU CHEN-HSIEN,WANG HWEI-CHUNG et al.Contribution of personalized Cyclin D1 genotype to triple negative breast cancer risk[J]. Biomedicine(Taipei), 2014, 4(1):3.
[29] ZHANG S, SHAO YB, HOU GF, et al. QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway in triple-negative breast cancer[J].Tumour Biol, 2014, 35(3):1847-1854.
[2] MOINFAR F. Is‘basal-like’carcinoma of the breast a distinct clinicopathological entity? A critical review with cautionary notes[J].Pathobiology, 2008, 75(2):119-131.
[3] BLEYER A, VINY A, BARR R. Cancer in 15-to 29-year-olds by primary site[J]. Oncologist, 2006, 11(6)590-601.
[4] LIU Y, XIN T, HUANG DY, et al. Prognosis in very young women with triple-negative breast cancer:retrospective study of 216 cases[J]. Med Oncol, 2014, 31(12):222.
[5] RHEE J, HAN SW, OH DY, et al. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer[J]. BMC Cancer, 2008, 8:307.
[6] AMIN MB, EDGE S, GREENE F, et al(eds). AJCC cancer staging manual, 8thEd[S]. Chicago, IL:Springer, 2017:589-636.
[7] LIEDTKE C, KENNETH HR, THOMAS K, et al. The prognostic impact of age in patients with triple-negative breast cancer[J]. Breast Cancer Research and Treatment, 2013, 138(2):591-599.
[8] SALMAN O, ALOK KD, ANTHONY LN, et al. Prognostic impact of age at diagnosis in triple negative breast cancer:Analysis of 204patients from single institution registry[J]. Journal of Clinical Oncology, 2018, 36(15):e13130.
[9] VERONESI U, CASCINELLI J, MARIANI L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radicalmastectomy for early breast cancer[J]. N Engl J Med,2002, 347(16):1227-1232.
[10] FISHER B, ANDERSON S, BRYANT J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer[J]. N Engl J Med, 2002, 347(16):1233-1241.
[11]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2017年版)[J].中国癌症杂志, 2017, 27(9):695-760.
[12] RAKHA EA, EL-SAYED ME, GREEN AR, et al. Prognostic markers in triple-negative breast cancer[J]. Cancer, 2007, 109(1):25-32.
[13] YUAN ZY, WANG SS, GAO Y, et al. Clinical characteristics and prognosis of triple-negative breast cancer:a report of 305 cases[J].Ai Zheng, 2008, 27(6):561-565.
[14] KWON J, EOM KY, KOO TR, et al. A prognostic model for patients with triple-negative breast cancer:importance of the modified nottingham prognostic index and age[J]. J Breast Cancer, 2017, 20(1):65-73.
[15] CANCELLO G, MAISONNEUVE P, MAZZA M,et al. Pathological features and survival outcomes of very young patients with early breast cancer:how much is"very young"?[J]. Breast, 2013, 22(6):1046-1051.
[16]李云,穆兰,阮玉霞,等.乳腺癌分子分型对保乳手术安全性的影响[J].中华肿瘤杂志, 2018, 40(5):341-346.
[17] ADKINS FC, GONZALEZ-ANGULO AM, LEI X, et al. Triple-negative breast cancer is not a contraindication for breast conservation[J].Ann Surg Oncol, 2011, 18(11):3164-3173.
[18] RADOSA JC, EATON A, STEMPEL M, et al. Evaluation of local and distant recurrence patterns in patients with triple-negative breast cancer according to age[J]. Ann Surg Oncol, 2017, 24(3):698-704.
[19] PILEWSKIE M, GORODINSKY P, FOUGHT A,et al. Association between recency of last pregnancy and biologic subtype of breast cancer[J]. Ann Surg Oncol, 2012, 19(4):1167-1173.
[20] BLADSTR?M A, ANDERSON H, OLSSON H. Worse survival in breast cancer among women with recent childbirth:results from a Swedish population-based register study[J]. Clin Breast Cancer,2003, 4(4):280-285.
[21] JOHANSSON ALV, ANDERSSON TML, HSIEH CC, et al. Tumor characteristics and prognosis in women with pregnancy-associated breast cancer[J]. Int J Cancer, 2018, 142(7):1343-1354.
[22] AZIM HA, SANTORO L, RUSSELL EW, et al. Prognosis of pregnancy-associated breast cancer:a meta-analysis of 30 studies[J].Cancer Treat Rev, 2012, 38(7):834-842.
[23] NAN S, JI YC, HYUNA S, et al. Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival[J].PLoS One, 2015, 10(4):e0123994.
[24] DANA CZ,FELICIA C,RAMONA S, et al. Relationship between reproductive risk factors, tumor characteristics and survival in breast cancer molecular groups[J]. Journal of Advances in Biology, 2016, 8(3):1646-1654.
[25] LUO HJ, LUO P, YANG GL et al. G-protein coupled estrogen receptor 1 expression in primary breast cancers and its correlation with clinicopathological variables[J]. J Breast Cancer, 2011, 14(3):185-190.
[26] YU T, LIU M, LUO H, et al. GPER mediates enhanced cell viability and motility via non-genomic signaling induced by 17β-estradiol in triple-negative breast cancer cells[J]. J Steroid Biochem Mol Biol,2014, 143:392-403.
[27] VIHKO R, APTER D. Endocrine characteristics of adolescent menstrual cycles:impact of early menarche[J]. Steroid Biochem, 1984,20(1):231-236.
[28] LIU LIANG-CHIH,SU CHEN-HSIEN,WANG HWEI-CHUNG et al.Contribution of personalized Cyclin D1 genotype to triple negative breast cancer risk[J]. Biomedicine(Taipei), 2014, 4(1):3.
[29] ZHANG S, SHAO YB, HOU GF, et al. QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway in triple-negative breast cancer[J].Tumour Biol, 2014, 35(3):1847-1854.