Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma:a matched comparative study

Background- To compare two types of therapy for primary breast carcinoma, breast-conserving therapy （BCT） and modified radical mastectomy （MRM）, in a matched cohort study. Methods： A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence （LR）, distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1：1, and each arm included 873 patients. Results： The median follow-up period was 71 months. The 6-year disease-free survival （DFS） and 6-year distant disease-free survival （DDFS） rates differed significantly between two groups. The 6-year local recurrence-free survival （LRFS） rates were 98.2% [95% confidence interval （CI）： 0.973-0.989] in the BCT group and 98.7% （95% CI： 0.980-0.994） in the MRM group （P=0.182）, respectively. DFS rates in BCT and MRM groups were 91.3% （95% CI： 0.894-0.932） and 86.3% （95% CI： 0.840-0.886） （P〈0.001）, respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% （95% CI： 0.922-0.950） and 87.7% （95% CI： 0.854-0.900） （P〈0.001）, respectively. Conclusions： BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.

Factors Predicting the Relapse of Radiation-Induced Organizing Pneumonia after Breast-Conserving Therapy

We investigated the factors predicting radiation-induced organizing pneumonia (RIOP) relapse after tangential breast irradiation. The participants included 23 patients diagnosed with RIOP at the St. Marianna University School of Medicine Hospital between January 2008 and March 2015. Relapse was defined as the appearance of new lesions on diagnostic images during follow-up or after commencing treatment. The relapse-free survival rate and the following 9 parameters were compared between patients with and without RIOP relapse: 1) age (less than vs. equal to or more than the median);2) white blood cell count (less than vs. equal to or more than the median);3) C-reactive protein (CRP) level at the time of RIOP diagnosis (less than normal, more than normal/ less than borderline, and more than borderline);4) boost irradiation (yes vs. no);5) maximum lung depth on linacgraphy (less than vs. equal to or more than the median);6) hormone therapy (yes vs. no);7) chemotherapy (yes vs. no);8) RIOP ratio in the whole lung (less than vs. equal to or more than the median) at the time of RIOP diagnosis;and 9) use of corticosteroids (yes vs. no). The Kaplan-Meier method was used for statistical analysis, with relapse as the cutoff. The follow-up period spanned the date of RIOP onset to May 30, 2015. The level of significance for 2-sided tests was p < 0.05. Relapse was evident in 14 patients (60.8%). The relapse-free survival rate was significantly greater in the normal CRP group (less than 0.30 mg/dl) than in the abnormal CRP group (more than 0.36 mg/dl) (p = 0.044) and in the normal/borderline CRP group (less than 0.36 mg/dl) than in the high CRP group (more than 0.70 mg/dl) (p < 0.01). The CRP level at RIOP onset may be a useful predictor of relapse after breast-conserving therapy.We investigated the factors predicting radiation-induced organizing pneumonia (RIOP) relapse after tangential breast irradiation. The participants included 23 patients diagnosed with RIOP at the St. Marianna University School of Medicine Hospital between January 2008 and March 2015. Relapse was defined as the appearance of new lesions on diagnostic images during follow-up or after commencing treatment. The relapse-free survival rate and the following 9 parameters were compared between patients with and without RIOP relapse: 1) age (less than vs. equal to or more than the median);2) white blood cell count (less than vs. equal to or more than the median);3) C-reactive protein (CRP) level at the time of RIOP diagnosis (less than normal, more than normal/ less than borderline, and more than borderline);4) boost irradiation (yes vs. no);5) maximum lung depth on linacgraphy (less than vs. equal to or more than the median);6) hormone therapy (yes vs. no);7) chemotherapy (yes vs. no);8) RIOP ratio in the whole lung (less than vs. equal to or more than the median) at the time of RIOP diagnosis;and 9) use of corticosteroids (yes vs. no). The Kaplan-Meier method was used for statistical analysis, with relapse as the cutoff. The follow-up period spanned the date of RIOP onset to May 30, 2015. The level of significance for 2-sided tests was p < 0.05. Relapse was evident in 14 patients (60.8%). The relapse-free survival rate was significantly greater in the normal CRP group (less than 0.30 mg/dl) than in the abnormal CRP group (more than 0.36 mg/dl) (p = 0.044) and in the normal/borderline CRP group (less than 0.36 mg/dl) than in the high CRP group (more than 0.70 mg/dl) (p < 0.01). The CRP level at RIOP onset may be a useful predictor of relapse after breast-conserving therapy.

Correlation of radiotherapy with prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping

Objective: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer.Methods: A retrospective analysis of 327 patients aged ≥65 years, with stage I-II, hormone receptor-positive breast cancer who underwent breast-conserving surgery and received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease-free survival(DFS), local relapse rate(LRR), overall survival(OS), and distant metastasis rate(DMR).Results: There were significant differences in 5-year DFS [hazard ratio(HR)=1.59, 95% confidence interval(95% CI), 1.15-2.19;P=0.005] and LRR(HR=3.33, 95% CI, 1.51-7.34;P=0.003), whereas there were no significant differences in OS and DMR between ET group and ET+RT group. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS and DMR between ET group and ET+RT group. In luminal B type,there were statistically significant differences in 5-year DFS(HR=2.19, 95% CI, 1.37-3.49;P=0.001), LRR(HR=5.45, 95% CI, 1.65-17.98;P=0.005), and OS(HR=1.75, 95% CI, 1.01-3.05;P=0.048) between ET group and ET+RT group. In the ET group, there were significant differences between luminal A type and luminal B type in5-year DFS(HR=1.84, 95% CI, 1.23-2.75;P=0.003) and OS(HR=1.76, 95% CI, 1.07-2.91;P=0.026).Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy.Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.

Current status of therapy for breast cancer worldwide and in Japan

The results of clinical trials conducted in Europe and North America have been incorporated into treatment strategies for breast cancer in Japan.Despite the use of similar treatment regimens,why has mortality from breast cancer been increasing in Japan?Procedures for surgical treatment and sentinel lymph node biopsy in breast cancer do not differ between Japan and Western countries,but the strategies for radiotherapy differ slightly.Hormonal therapy is now selected on the basis of scientific evidence,and similar regimens are used in Japan and Western countries.As for postoperative adjuvant chemotherapy,an anthracycline plus cyclophosphamide and taxane-based regimens are standard treatments in Japan and Western countries.In 2009,however,the results of two large clinical studies designed to determine whether intravenous or oral treatment was superior for postoperative adjuvant chemotherapy were reported in Japan.Both studies showed that relapsefree survival and overall survival(OS)at 5 years after surgery were similar for a combination of cyclophosphamide,methotrexate,and 5-fluorouracil and for tegafur/uracil.Many chemotherapeutic agents that are used to treat recurrent or metastatic breast cancer have not yet been approved in Japan.As for molecular targeted therapy,some agents that target the human epidermal growth factor receptor family have been approved in Japan,whereas angiogenesis inhibitors have not.The results of many clinical trials have been incorporated into clinical practice in Japan,therefore,the outcomes of breast cancer therapy have surpassed those in other countries.Many pivotal clinical trials have been conducted outside Japan.Treatment regimens that have been developed on the basis of these studies might be suitable for the management of breast cancer in Western women,but not for Japanese women because of differences in genetic factors,physique,body mass index,pharmacokinetics,and drug metabolism.Such regimens should be modified on the basis of the characteristics of breast cancer in Japan to develop treatment that is optimally suited for Japanese women.In particular,local studies of pharmacokinetics,pharmacodynamics,and optimal dose levels and treatment intervals should be carefully performed.The establishment of treatment regimens optimally suited for Japanese patients with breast cancer could put the brakes on the trend towards increasing mortality from breast cancer in Japan.

Quantitative Assessment of Chronic Skin Reactions Including Erythema and Pigmentation after Breast Conserving Therapy

Purpose: To evaluate long-term skin reactions following breast-conserving therapy by using the melanin-erythema index meter. Patients and Methods: 164 patients were followed for at least three years after breast-conserving therapy. For both the erythema and the melanin indices, the ratio of the irradiated-side index to the non-irradiated-side index was calculated. The time course of index ratios alternation was examined. Influences from additional therapies and patients’ age were also evaluated. Result: Both erythema and melanin index ratios of the breast skin were recovered to pre-radiation level three years after radiotherapy. However, both index ratios of the area administrated with 10-Gy boost irradiation were still high even after five years after radiotherapy. Endocrine therapy, chemotherapy and age had no significant influence on skin color reactions three years after radiotherapy. Conclusion: Quantitative assessment using the melanin-erythema index meter demonstrated that chronic skin reactions following breast conserving therapy had recovered to pre-radiation level for three years after irradiation except for the 10-Gy boost irradiated area.

Age exerts a continuous effect in the outcomes of Asian breast cancer patients treated with breast-conserving therapy

Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.Methods:Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed.The Kaplan-Meier method was used to estimate locoregional recurrence,breast cancer-free survival,and breast cancer-specific survival rates.These rates were then compared using log-rank tests.Outcomes and age were modeled by Cox proportional hazards.Fractional polynomials were then used to test for non-linear relationships between age and outcomes.Results:Patients≤40 years old were more likely to have locoregional recurrence than were older patients(Hazard ratio[HR]=2.32,P<0.001).Locoregional recurrence rates decreased year-on-year by 4%for patients with luminal-type breast cancers,compared with 8%for those with triple-negative cancers.Similarly,breast cancer-free survival rates increased year-on-year by 4%versus 8%for luminal-type and triple-negative cancers,respectively.Breast cancer-spe-cific survival rates increased with age by 5%year-on-year.Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear(“L-shaped”)relationship-where decreasing age at presentation was associated with escalating risks of relapse and death.The influence of age on overall survival was confounded by competing non-cancer deaths in older women,resulting in a“U-shaped”relationship.Conclusions:Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.

Is surgical axillary staging necessary in women with T1 breast cancer who are treated with breast-conserving therapy?

Background:In the post-Z0011 trial era,the need to perform surgical axillary staging for early-stage breast cancer patients,who are treated with breast-conserving therapy(BCT),is being questioned.We conducted a retrospective cohort study using the Surveillance,Epidemiology,and End Results(SEER)database to evaluate the safety of waiving surgical axillary staging in patients with T1 breast cancer treated with BCT.Methods:A total of 166,615 eligible patients diagnosed between 2000 and 2012 were divided into staging(sentinel lymph node biopsy or axillary lymph node dissection)and non-staging(no lymph node examined or only needle aspiration biopsy of lymph nodes)groups.Propensity score matching(PSM)was performed to balance disparities between the two groups.Multivariate analysis with the Cox proportional hazards model was used to assess factors related to breast cancer-specific survival(BCSS).Results:Although the tumor size at time of presentation was decreasing over years,the rate of surgical axillary stag-ing increased from 93.3%to 96.9%.The 5-year BCSS rates of the whole cohort(before PSM)and matched cohort(after PSM)were 98.0%and 97.5%.Within the matched cohort,the BCSS was significantly longer in the staging group than in the non-staging group(P<0.001).However,surgical axillary staging did not benefit patients who were 50-79 years old,had tumor size<1 cm,histological grade I disease,or favorable histological types(tubular/mucinous/papillary)in stratified analyses(P>0.05).Race,marital status,hormone receptors,and chemotherapy were not associated with the favorable impact of surgical axillary staging on BCSS(P>0.05).Conclusion:Although surgical axillary staging remains important for T1 breast cancer patients treated with BCT,it might be unnecessary for patients with old age,small tumor,grade I disease,or favorable histological types.

乳腺癌保乳术切缘刮片细胞学与快速组织学诊断的对比研究

目的:探讨术中切缘刮片细胞学与快速病理组织学对乳腺癌保乳术切缘的诊断价值。方法:6例患者行乳腺癌保乳术,术中对乳腺癌切缘行细胞学刮片同时取活检行快速组织学观察,并与术后病理诊断对比研究。结果:6例共24次切缘刮片细胞学诊断错误1次,冰冻检查诊断错误1例,两者联合应用诊断正确率100%。结论:术中刮片细胞学快速实用,与快速组织学检查同时使用可提高残端癌的检出率,同时掌握好乳腺导管上皮内瘤变的刮片细胞学形态,可更好预测残端癌发生的危险性。

早期乳腺癌保乳手术临床分析

目的通过与改良根治术比较,探讨乳腺癌保乳手术的临床疗效。方法选择我院自2001年1月～2004年1月早期乳腺癌患者96例,实施保乳手术48例和改良根治术48例,并对两者的临床疗效进行对比研究。结果全部患者随访48+个月,均无瘤生存,观察组优良45例,优良率达93.7%。对照组优良12例,优良率达25.0%。观察组与对照组比较,患者美容效果满意率更高。结论对早期乳腺癌患者,在严格掌握适应证的前提下保留乳房是切实可行的,术后结合正规化疗、放疗及内分泌治疗,取得满意疗效。

5-ALA介导的光动力治疗在耐药白血病中的作用机制研究

目的:本研究观察了5-氨基乙酰丙酸介导的光动力治疗(ALA-PDT)对耐药白血病细胞株HL-60/ADR的杀伤作用及对耐药白血病原代细胞存活率的影响。方法:以耐药白血病细胞株HL-60/ADR为实验模型,同时在11例白血病患者原代细胞中进行检测。实验分为4组,对照组、单纯ALA组、单纯光照组及ALA+PDT组。用MTT法测定细胞的存活率,采用阳离子脂质荧光探针JC-1检测线粒体跨膜电位,用Real-time PCR检测PDT前后HL-60/ADR细胞株中bcl-2基因及多药耐药基因MRP的表达变化。结果:ALA-PDT后HL-60/ADR细胞株线粒体跨膜电位出现快速下降,0,2,4h时线粒体跨膜电位崩塌的细胞比例分别升高至55.91%±2.60%、64.27%±1.08%、82.17%±0.43%,与对照组相比皆有显著差异(P<0.05),呈时间依赖性。而单纯ALA组和单纯光照组则无明显变化。HL-60/ADR细胞株在ALA-PDT后Bcl-2和MRP基因均呈明显下降趋势。在初发和复发难治急性白血病原代细胞中ALA+PDT组均显示较强的光动力效应。结论:ALA-PDT诱导的HL-60/ADR细胞的杀伤可能与其影响线粒体跨膜电位有关,即通过影响线粒体功能促进细胞凋亡。同时表明ALA介导的光动力作用部分是通过在基因转录水平下调抗凋亡基因Bcl-2而促进凋亡的发生,另一方面通过下调耐药基因MRP的表达而部分逆转耐药。同时ALA-PDT对原代白血病细胞同样有较大的抑制作用。