Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer

Risk factors for local-regional recurrence of breast cancer were analyzed in a retrospective review of 117 patients treated with adjuvant CMF (Cytoxan [Mead Johnson & Co, Evansville, Ind], methotrexate, 5-fluorouracil) after radical or modified radical mastectomy at the Vincent T. Lombardi Comprehensive Cancer Center (Washington, DC). The median follow-up time was 50 months after mastectomy. The median time to recurrence was 23 months. The actuarial local-regional failure rate was 19% at five years. Risk of local failure correlated with size of primary (27% for T3 v 15% for T1) and axillary node status (36% for four or more positive nodes v 9% for three or fewer positive nodes). These findings suggest a rationale for the addition of postoperative radiation therapy in high-risk patients treated with adjuvant chemotherapy.     

乳腺癌保留乳房手术后的放射治疗技术

放射治疗是早期乳腺癌保乳治疗的一个不可缺少的部分。荟萃分析显示：保乳术后放射治疗可以降低同侧乳腺肿瘤的复发率和患者的癌症病死率,放射治疗和未放射治疗患者的5年同侧乳腺局部复发率分别为79／6和26％,15年乳腺癌病死率分别为30．5％和35．9％。目前早期乳腺癌保乳术后放射治疗主要包括全乳房照射50．0Gy（每次2．0Gy）,然后瘤床补量照射10．O～16．0Gy。     

Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy

To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.     

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

C onservative surgery for early breast cancer was proposed by Keynes in 1924 and has been one of the main therapeutic mea- sures. It has been confirmed by abundant literature that the efficacy of conservative surgery plus whole breast radiotherapy is the …     

Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.     

乳腺癌术后含表柔比星化疗和辅助放疗后心电图异常的临床分析

目的探讨乳腺癌患者手术后采用表柔比星化疗和辅助放疗心电图异常的影响因素。方法选取51例乳腺癌术后采用表柔比星化疗和辅助放疗患者的临床资料进行分析,分析心电图异常与年龄、肿瘤部位、基础疾病、内分泌治疗、含表柔比星累积剂量和放疗方式之间的关系。结果11例患者出现心电图异常,占21.6%;年龄≥50岁、伴有基础疾病、含表柔比星累积剂量≥400 mg和电子线放疗方式患者的心电图异常率显著高于年龄<50岁、未伴有基础疾病、含表柔比星累积剂量<400 mg和调强放疗方式患者,差异均有统计学意义(均P<0.05)。结论乳腺癌术后采用表柔比星化疗后辅助放疗导致的心电图异常与患者年龄、基础疾病、含表柔比星累积剂量和放疗方式有一定关系。     

早期乳腺癌保乳术后放化疗的最佳顺序

目的 探讨早期乳腺癌保乳治疗后放化疗最佳顺序，使保乳治疗的局部控制、远处转移和保乳效果达到最佳。方法 2000年1月～2002年11月，对38例符合保乳治疗条件的早期乳腺癌实施了保乳治疗。手术方式为局部广泛切除术和腋窝淋巴结清扫，术后2周开始化疗，化疗2周期后再开始放疗，全乳剂量50Gy，瘤床补充照射10～18Gy。放疗结束后根据使用化疗方案选择立即化疗或休息1周后再开始化疗，化疗共6周期。治疗结束后每3个月复查1次，放疗后6个月行乳房钼靶摄影。此后1年1次乳房照片检查。结果 38例保乳治疗的患者均定期复查，中位随访24个月(5～35个月)。未发现局部复发和远处转移。放疗后1年或以上的28例患者乳房外观良好。结论 早期乳腺癌保乳治疗中“三明治”式放化疗能满足保乳治疗的目的。     

乳腺癌保乳术后放化疗５２例临床观察

目的　观察乳腺癌保乳术后放射治疗的疗效及毒副反应。方法　对可行保乳术的５２例患者行肿瘤切除或加腋窝淋巴结清扫,术后采用放疗联合辅助化疗。６ＭＶ-Ｘ线全乳腺双切线半野照射,照射剂量４５～５０Ｇｙ,局部瘤床采用１０～１５ＭｅＶβ线加量１０～２０Ｇｙ,总剂量５６～６６Ｇｙ;化疗采用ＣＡＦ或ＴＥ方案。结果　５２例患者均获随访,其１、２和３年生存率分别为９８.１％、９２.３％和９０.４％,３年局部复发率为５.７7％,乳房美容满意率达９０.４％。４０例（７６.９％）患者发生了１、２级放化疗毒副反应,主要为白细胞减少。结论　早期乳腺癌采用保乳手术加放化疗可取得满意疗效,且保留乳房的美容效果佳。     

Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy.

PURPOSE: The aim of the present study was to evaluate the role of local failure (LF) in the survival of patients treated with lumpectomy and postoperative radiotherapy and to investigate whether LF is not only a marker for distant metastasis (DM) but also a cause. METHODS: Charts of patients treated with breast conservative surgery between 1969 and 1991 were reviewed retrospectively. There were 2,030 patients available for analysis. The median duration of follow-up was 6 years. A Cox regression multivariate analysis was performed using LF as a time-dependent covariate. RESULTS: Local control (LC) was 87% at 10 years. Local failure led to poorer survival at 10 years than local control (55% v 75%, P < .00). In a Cox model, local failure was a powerful predictor of mortality. The relative risk associated with LF was 3.6 for mortality and 5.1 for DM (P < .00). In patients with LF, the rate of DM peaked at 5 to 6 years, whereas it peaked at 2 years for patients with LC. The mean time between surgery and DM was 1,050 days for patients without LF and 1,650 days for patients with LF (P < .00). CONCLUSION: Our results show that local failure is associated with an increase in mortality. The difference in the time distribution of distant metastasis for LF and LC could imply distinct mechanisms of dissemination. Local failure should be considered not only as a marker of occult circulating distant metastases but also as a source for new distant metastases and subsequent mortality.     

早期乳腺癌保乳术后局部复发与术后放疗可行性的分析

目的总结早期乳腺癌保乳手术后局部复发的表现,分析全乳放疗的作用。方法保乳治疗原发性早期乳腺癌134例,其中0期1例,Ⅰ期78例,Ⅱa期55例。行象限切除加腋窝淋巴结清扫术125例,单纯肿块局部广泛切除术9例。术后全乳切线加瘸床放疗102例,全乳切线照射整个乳房,6 MV X线,为减少肺受照量,采用半开野等中心照射,中平面剂量45 Gy,瘤床补加电子束剂量15 Gy。其余32例未行全乳放疗。视术后淋巴结状况行区域淋巴引流区照射。结果随访5～15年,失访5例。术后5年局部复发率、远处转移率、生存率分别为3．7%、2．2%、95．5%。复发共5例,均为浸润性癌,术后病理证实区域淋巴结均为阴性。保乳术后不加全乳放疗组局部复发率似有所提高（9．4%∶2．0%）,但差异无统计学意义,可能与病例数少有关。局部复发病例中原位复发4例。结论结论保乳术后放疗是必要的。局部复发的主要形式是原位复发。足够剂量的只限于肿瘤邻近区域的放疗方式应该是可行的。     

Salvage chemotherapy for breast cancer patients treated with adjuvant adriamycin-containing regimen

Purpose of this study was to evaluate the efficacy of salvage chemotherapy given to women with breast cancer in relapse who had in the past received adjuvant treatment including adriamycin. Fourty-nine evaluable patients had an adjuvant chemotherapy with CMFAV in 6 or 12 cycles. On relapse these patients received either adriamycin 40 mg/m2, mitomycin 8 mg/m2 and vinblastine 6 mg/m2 (group A) or dibromodulcitol 500 mg, mitomycin 8 mg/m2 and vinblastine 6 mg/m2 (group B). In Group A, 22 patients with a mean age of 49.2 years relapsed 14 months on average after the end of adjuvant treatment. In 11 of them the main site of relapse was visceral. In group B, 27 patients with a mean age 49.5 years relapsed 6.5 months on average after the end of adjuvant treatment. In 15 of them the main site of relapse was visceral. According to the disease-free interval (DFI), in group A with DFI less than 12 months 3 patients (23%) responded partially whereas in patients with DFI longer than 12 months 4 patients (44.4%) had a partial response. In group B with DFI less than 12 months 4 patients (21%) responded partially, whereas 2 (25%) responded with DFI longer than 12 months. We conclude that salvage chemotherapy in this group of patients with an adriamycin-containing regimen is superior to a non-adriamycin regimen only if the DFI is longer than 12 months.     

A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy

Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy.In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1–21 or 1–8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombinantithrombin complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI - 1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods. t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle.A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1–21 group (mean ± SD = 72.5 ± 10.8%) and in the CMF 1–8 group (mean ± SD = 77.2 ± 6.9%); PC activity was also decreased. PS antigen decreased after the first administration (mean ± SD = 73.3 ± 10% in CMF 1–21 group, and 72.5 ± 4.9% in CMF 1–8 group); PS activity also decreased. PAI-1 antigen levels increased (mean ± SD = 43.1 ± 20.4 ng/ml in the CMF 1–21 group, and 37.5 ± 12.2 ng/ml in CMF 1–8 group) lasting up to the last cycle.CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.C.R. is a recipient of a fellowship from the Italian Association for Cancer Research (A.I.R.C.)     

乳腺癌术后辅助化疗患者营养风险状况及其对化疗不良反应的影响

 目的 观察乳腺癌术后辅助化疗患者的营养风险状况及其对化疗不良反应的影响。方法 选取营养风险筛查量表2002（nutritional risk screening 2002,NRS 2002）评分＜3分的乳腺癌术后患者96例,化疗6个周期后再次评估,根据NRS 2002评分,≥3分为营养风险组,＜3分为无营养风险组,分析两组临床资料、营养风险状况、不良反应及住院天数。结果 96例乳腺癌患者术后辅助化疗6个周期后,NRS 2002评分≥3分者39例,营养风险发生率为40.6%;两组患者月经情况、雌激素受体/孕激素受体（ER/PR）、人表皮生长因子受体2（cerbB-2）、细胞增殖指数（Ki-67）、临床分期、化疗药物相对剂量强度等临床资料比较,差异均无统计学意义（P均＞0.05）。两组化疗前后血红蛋白、血白蛋白、总淋巴细胞计数、肱三头肌皮褶厚度等营养指标的差异均无统计学意义（P均＞0.05）;营养风险组体重指数（BMI）化疗前后比较差异有统计学意义（P＜0.05）,无营养风险组BMI化疗前后比较差异无统计学意义（P＞0.05）,化疗后两组BMI比较差异有统计学意义（P＜0.05）。营养风险组Ⅲ级/Ⅳ级主要不良反应为中性粒细胞减少、血红蛋白减少、血小板减少、恶心呕吐、口腔黏膜炎、肝功能异常、疲乏等,其发生率及住院时间均高于无营养风险组（P均＜0.05）。 结论 乳腺癌术后辅助化疗期的患者存在较高的营养风险发生率,及早评估和发现其营养风险,有助于预测患者的化疗风险,减少化疗不良反应的发生。     

Tolerance of radiotherapy combined with adjuvant chemotherapy in breast cancer

Forty-three postmenopausal breast cancer patients with axillary lymph node metastasis were randomized to receive postoperative radiotherapy (45 Gy) or the combination of radiotherapy and 6 months of chemotherapy. Forty-three premenopausal patients had postoperative radiotherapy and were randomized to receive one of two different chemotherapy combinations. Pulmonary fibrosis was roentgenologically registered in approximately 70 per cent of the total patient population six months after initiation of therapy. Addition of chemotherapy with doxorubicin and cyclophosphamide significantly increased the proportion of patients with pulmonary fibrosis compared with patients treated with radiotherapy only or radiotherapy combined with cyclophosphamide, methotrexate and 5-fluorouracil. Premenopausal patients tolerated the combination of radiotherapy and chemotherapy better than postmenopausal patients of whom approximately 30 per cent did not tolerate 65 per cent or more of prescribed total dose of chemotherapy.     

Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer

The time-course of local failure following conservative surgery and radiotherapy (S+RT) for early breast cancer is not well established. We therefore examined the time-course and patterns of breast recurrence as a first site of treatment failure in a group of 607 AJCC clinical Stage I or II invasive breast carcinomas treated from 1968-81. Sixty-seven patients had a breast failure (11%), corresponding to 5- and 10-year actuarial rates of 10% and 16%. The hazard rate (i.e., the risk per unit time of a failure) for any breast failure increased over the first 2 years, was fairly constant at about 2.5%/year over the period from 2 to 6 years after treatment, and then decreased to about 1%/year at 8 years. The majority of failures were at or near the primary tumor site (33 true recurrences (TR) and 15 marginal misses (MM). In addition there were 12 failures at sites at least several cm from the boosted volume (E), 6 recurrences in the skin without a parenchymal mass (S), and 1 patient with an unclassifiable failure. Recurrences at or near the primary site (TR/MM) occurred earlier (median 38.5 mo, range 12-87 mo) than recurrences at distant sites in the breast (E) (median 64.5 mo, range 26-90). The hazard rate for TR/MM increased over the first 2-1/2 years to reach approximately 2%/year, remained at that level till about 5 years after treatment, and then decreased to about 0.5%/year at 8 years following RT. By contrast, the hazard rate for E increased slowly with time to approximately 1%/year at 5 years, with little change in the rate after that time. We conclude that the time-course of the development of local recurrence after S+RT is protracted. The majority of failures appear at or near the primary tumor site; these are seen mainly in the first 7 years following RT. Recurrences at distant sites in the breast have an even more protracted time-course. Such recurrences are rare in the first 4 years following RT. Our results emphasize the need to obtain long follow-up in these patients, both to detect these recurrences promptly and to properly evaluate the results of S+RT.     

Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant chemotherapy alone in premenopausal breast cancer patients with positive axillary nodes

AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, "Istituto del Radio O. Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta Foundation" (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases. RESULTS: A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).     

Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen: fifteen-year results of a prospective study

BACKGROUND: In elderly patients with early breast cancer and a clinically clear axilla, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients. METHODS: The authors followed 354 prospectively recruited women aged > or =70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. All 354 women were treated with conservative surgery and adjuvant tamoxifen and without axillary dissection or postoperative radiotherapy. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality. RESULTS: After a median follow-up of 15 years (interquartile range, 14-17 years), the crude cumulative incidence was 4.2% (4% in pathologic T1 [pT1] tumors) for axillary disease, 8.3% (7.3% in pT1 tumors) for IBTR, and 17% for breast cancer mortality. Of the 268 patients who died during follow-up, 222 patients (83%) died from causes unrelated to breast cancer. CONCLUSIONS: Elderly patients with early breast cancer and no palpable axillary lymph nodes may be safely treated safety by conservative surgery without axillary dissection and without postoperative radiotherapy, provided that surgical margins are in tumor-free tissue and that hormone therapy is administered. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease.