早期乳腺癌保乳术后的放疗时机

早期乳腺癌保留乳房手术加放疗的疗效与根治术相同。对术后放疗时机的问题有一些回顾性和随机性研究,但无明确结论,近期的一些随机研究尚需要长期随访。总的来说,对于无需术后化疗的病人应尽早放疗,建议手术放疗间隔最好不超过8周。术后放疗、化疗顺序对疗效无显著影响,先放疗或先化疗均可以。对于腋窝淋巴结转移数较多的远地转移高危病人,术后可先做辅助化疗,但放疗不应延迟到术后7个月以后。如果手术切缘阳性,放疗应尽早开始。同步放化疗可以在不延迟放化疗的基础上提高局部疗效,但疗效提高有限,同时会增加急性和晚期毒副作用,不宜作为常规治疗。特殊病人需要使用时,应选择有效低毒的化疗方案,以降低治疗带来的急性毒副作用和晚期并发症。缩短放疗总时间对需要化疗的病人可以缩短手术到化疗的时间间隔,目前可行的方式有大分割放疗和乳腺瘤床同步补量技术。缩短放疗总时间是否能对疗效改善有影响,有待于临床资料证实。     

A phase III randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer

PURPOSE: To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. METHODS AND MATERIALS: A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10-15 Gy in 4-6 fractions to the tumor bed. RESULTS: No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups. CONCLUSIONS: In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters.     

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。     

Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma.

PURPOSE: The study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma. PATIENTS AND METHODS: Between 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow-up was 50 months (range, 20 to 80 months). Cosmesis was graded by defined criteria, and complications were individually scored. RESULTS: Factors found to impact cosmesis adversely were palpable tumors (P = .046), volume of breast tissue resected (P = .027), reexcision of the tumor bed (P = .01), number of radiation fields (P = .03), radiation boost (P = .01), and chest wall separation (P = .01). There was a trend toward worse cosmesis (P = .062) in patients receiving tamoxifen. Cosmesis was not adversely affected by interstitial implant in spite of a higher prescribed dose. Factors influencing complication risk were axillary node dissection (P = .02), number of lymph nodes harvested (P = .05), and chemotherapy (P = .03). CONCLUSIONS: Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy. The impact of systemic therapies needs to be more thoroughly examined.     

Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma

We retrospectively analyzed the likelihood of regional nodal failure (RNF) for 1,624 patients with stage I or II invasive breast carcinoma treated with conservative surgery and radiotherapy (RT) at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. The median follow-up time was 77 months. RNF was the first site of failure for 38 of the 1,624 patients (2.3%). The incidence of axillary failure for patients undergoing axillary dissection (AXD) who were irradiated to the breast only was 2.1% (nine of 420) for patients with negative nodes and 2.1% (one of 47) for patients with one to three positive nodes. The incidence of supraclavicular failure in these two groups was 1.9% (eight of 420) and 0% (zero of 47), respectively. The incidences of axillary and supraclavicular failure in patients without clinically suspicious axillary involvement who did not have AXD but were treated with RT were 0.8% (three of 355) and 0.3% (one of 364), respectively. Despite various combinations of salvage surgery, RT, and systemic therapy, only 47% of patients (18 of 38) achieved complete regional control after nodal relapse. We conclude that RNF is uncommon in patients treated to the breast alone following an adequate AXD when the axillary nodes are negative or when one to three nodes are positive. RNF is also uncommon in patients with a clinically uninvolved axilla treated with nodal RT without AXD. Symptoms of RNF can be controlled in most but not all patients. Further study is needed to determine if the benefits of RT in preventing a small number of symptomatic RNF outweigh the potential toxicity for any subgroup of patients.     

早期乳腺癌保乳术后放疗美容效果及疗效观察

目的观察早期乳腺癌保乳术后常规放疗的美容效果及较远期疗效。方法进入研究的条件为单一病灶,肿块最大直径≤3 cm,显微镜下手术切缘阴性,腋窝淋巴结清扫为阴性。排除炎性乳腺癌和男性乳腺癌。42例0、Ⅰ、Ⅱ期乳腺癌保乳手术后使用6 MV X线切线野常规分割照射,全乳房照射50 Gy,局部瘤床区电子线补量照射10 Gy。治疗后2年内每3个月、第3-5年每6个月、之后每年随访1次,观察治疗和美容效果。结果全组病例随访19-90个月(中位随访56个月),2例分别在治疗后16、36个月因远处转移死亡,CT确诊。美容效果和患者满意度均超过93%。无一局部复发,局部控制率100%。1、3年生存率分别为100%、98%。结论早期乳腺癌保乳术后6 MV X线切线野照射疗效可靠、美容效果良好且急性和晚期毒性作用小,因此更有利于早期乳腺癌患者生活质量的提高。     

早期乳腺癌保乳术后调强适形放疗的应用

传统的保乳术后放疗方法是做全乳腺照射5～6周,引起的不良反应多见.随着放射治疗技术的发展,以最小的侵袭或损伤达到最佳疗效,已成为肿瘤学者追求的目标.调强适形放疗(IMRT)的发展有很大的空间,日益受到广大学者的重视,将可能会成为早期乳腺癌保乳术后的标准治疗方式.     

Skin-sparing radiation using intensity-modulated radiotherapy after conservative surgery in early-stage breast cancer: a planning study

PURPOSE: To evaluate the feasibility of skin-sparing by configuring it as an organ-at-risk (OAR) while delivering whole-breast intensity-modulated radiotherapy (IMRT) in early breast cancer. METHODS AND MATERIALS: Archival computed tomography scan images of 14 left-sided early-breast tumor patients who had undergone lumpectomy were selected for this study. Skin was contoured as a 4- to 5-mm strip extending from the patient outline to anterior margin of the breast planning target volume (PTV). Two IMRT plans were generated by the helical tomotherapy approach to deliver 50 Gy in 25 fractions to the breast alone: one with skin dose constraints (skin-sparing plan) and the other without (non-skin-sparing plan). Comparison of the plans was done using a two-sided paired Student t test. RESULTS: The mean skin dose and volume of skin receiving 50 Gy were significantly less with the skin-sparing plan compared with non-skin-sparing plan (42.3 Gy vs. 47.7 Gy and 12.2% vs. 57.8% respectively; p < 0.001). The reduction in skin dose was confirmed by TLD measurements in anthropomorphic phantom using the same plans. Dose-volume analyses for other OARs were similar in both plans. CONCLUSIONS: By configuring the skin as an OAR, it is possible to achieve skin dose reduction while delivering whole-breast IMRT without compromising dose profiles to PTV and OARs.     

Integration of systemic therapy and radiation therapy for patients with early-stage breast cancer treated with conservative surgery

There is no consensus on the optimal combination of systemic therapy and radiation therapy for patients with early-stage breast cancer treated with conservative surgery. This article reviews prospective and retrospective studies that shed light on this topic. Patients with positive, close, or unknown microscopic margins appear to benefit from relatively early initiation of radiation therapy, whereas those with wider tumor-free margin widths do not. For patients at high risk of distant failure (such as those with = 4 positive axillary nodes), chemotherapy may be more effective when it begins before radiation therapy rather than after. Regimens of concurrent radiation therapy and chemotherapy tend to have higher acute and subacute complication rates than sequential regimens, but the actual rates vary substantially with the exact details of the overall treatment program. There are no data on the impact of the timing of tamoxifen administration on the effectiveness of radiation therapy. Tamoxifen does not appear to increase complication rates relative to the use of radiation therapy alone. Thus, the best way of giving combined-modality therapy is uncertain. Further retrospective and prospective studies to investigate the issues discussed herein should be performed.     

Selection of adjuvant chemotherapy for treatment of node-positive breast cancer

Over the past two decades, several studies have suggested that regimens that contain anthracyclines are more effective than those that do not. A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group confirmed that about 6 months of anthracycline-based polychemotherapy in the adjuvant setting reduced the yearly death rate from breast cancer by about 38% for women younger than 50 years and by 20% for women aged 50-69 years. Although this meta-analysis found that survival was better with regimens that contain anthracycline than with regimens based on cyclophosphamide, methotrexate, and fluorouracil, the best use of anthracycline-based regimens remains unclear. Adjuvant regimens in use can be categorised into three groups: standard-dose anthracycline; escalated-dose epirubicin; and anthracyclines and taxanes. The duration of treatment and combination of dose and drugs varies between these three categories. We reviewed the three types of regimen to establish which provide a better outcome in terms of safety, efficacy, cost, and convenience to patients. We found that both escalated-dose epirubicin and anthracycline-taxane regimens were most effective in terms of disease-free survival and overall survival. Of the specific anthracycline-based regimens, the docetaxel, doxorubicin, and cyclophosphamide regimen (TAC); the fluorouracil, 100 mg epirubicin, and cyclophosphamide regimen (FEC100); and the cyclophosphamide, epirubicin, and fluorouracil regimen (CEF) produced the greatest proportional decreases in 5-year death rate.     

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

早期乳腺癌保乳术后调强放疗

现行早期乳腺癌保乳术后的常规切线野放射治疗技术存在靶区内剂量不均匀的缺陷.国内外多位研究者将调强放疗(IMRT)应用于保乳术后患者,以期在提高靶区剂量均匀性、降低危及器官受量及改善美容效果方面体现出一定优势.     

Prognosis after local recurrence after conservative surgery and radiation for early-stage breast cancer

PURPOSE: To determine the long-term prognosis of patients who develop a local recurrence (LR) after conservative surgery (CS) and radiation therapy (RT) for early-stage invasive breast cancer. METHODS AND MATERIALS: Between 1970 and 1987, 2102 patients with clinical Stage I-II breast cancer were treated with CS+RT. LR was defined as any recurrence within the ipsilateral breast with or without simultaneous regional nodal or distant metastasis. Patients were at risk for a LR until the first of distant metastases, second nonbreast malignancy, or death (DF/S/D). The final study population comprised 341 patients with LR. The median time to LR was 72 months. The median follow-up time after LR was 85 months. A proportional hazards model of time from LR to DF/S/D was done to investigate the influence of factors at initial diagnosis and at LR on subsequent outcome. RESULTS: The actuarial freedom from DF/S/D 5 years after LR was 65% and the survival was 81%. Variables significantly associated with time to DF/S/D were: LR histology (invasive vs. ductal carcinoma in situ, hazard ratio [HR] = 4.1, p < 0.0001); local therapy for LR (none vs. mastectomy or unknown, HR = 3.2, p < 0.0001; and CS +/- RT vs. mastectomy or unknown, HR = 2.0, p = 0.02); time to LR (< or =2 years vs. >5 years, HR = 2.6, p < 0.0001; and 2-5 years vs. >5 years, HR = 1.8, p = 0.006); and age at initial diagnosis (> or =60 vs. <60, HR = 1.6, p = 0.01). CONCLUSIONS: Many patients with LR after CS+RT have prolonged distant disease-free survival, particularly those able to be treated with mastectomy. Patients with a noninvasive LR, longer interval to LR, or age <60 had a longer time to distant failure, second malignancy, or death than other patients.     

Second nonbreast malignancies after conservative surgery and radiation therapy for early-stage breast cancer

PURPOSE: Breast cancer patients treated with conservative surgery and radiation therapy are at risk of developing second nonbreast malignancies (SNBMs). The purpose of this study was to determine the incidence of all SNBMs and SNBMs by specific location among long-term survivors and to compare the risk of these events to the age-specific incidence of malignancies as first cancers in the Surveillance Epidemiology and End-Results Program (SEER) population. METHODS AND MATERIALS: We analyzed the likelihood of SNBM development for 1884 patients with clinical Stage I or II breast cancer treated with gross excision and > or = 60 Gy (median 63) to the breast between 1970 and 1987. Fifty-seven percent received supraclavicular/axillary radiation (median dose 45 Gy, range 20-60) and 28% received systemic therapy. The median age at diagnosis was 52 years. The median clinical tumor size was 2 cm. Patients were considered at risk of an SNBM until the development of the first of distant metastases or contralateral breast cancer or death or, if alive and disease-free, until the last follow-up visit. The expected numbers of cancers were obtained from the SEER database, using the age-specific incidence for white women within 5-year age groups and 5-year calendar intervals. The median time at risk for an SNBM was 10.9 years (range 0.2-27.9). RESULTS: By 8 years of follow-up, 432 patients (23%) had developed distant metastases, 295 patients (16%) a local/regional recurrence, and 159 (8%) a contralateral primary. Of the 1884 patients in our cohort, 147 (8%) developed an SNBM compared with the 127.7 expected from SEER. This corresponds to an absolute excess of 1% of the study population and a relative increase of 15% greater than that expected from SEER (p = 0.05). Within the first 5 years, the observed and expected rates of SNBMs were identical (47 vs. 46.9). After 5 years, 24% more SNBMs were observed than expected (100 vs. 80.8, p = 0.02). Among patients <50 years old at breast cancer diagnosis, 43% more observed SNBMs occurred than expected (40 vs. 28, p = 0.02). For patients > or = 50 years, 7% more SNBMs were observed than expected (107 vs. 99.7, p = 0.25). Lung SNBMs were observed in 33 women, 52% more than the 21.67 predicted by SEER (p = 0.01). Most of the lung SNBMs occurred >5 years after treatment (n = 23) and in women who were >50 years at the time of their breast cancer diagnosis (n = 27). The observed incidence of ovarian cancer was significantly greater than expected among patients <50 years (7 vs. 1.96, p = 0.004) but was not different than expected for patients > or = 50 years (5 vs. 5.3, p = 0.61). Among the 7 sarcomas, 3 developed in the radiation field. CONCLUSIONS: SNBMs occur in a substantial minority (8%) of patients treated with conservative surgery and radiotherapy. However, the absolute excess risk compared with the general population is very small (1%). This excess risk is only evident after 5 years. In particular, a slightly increased incidence of lung SNBMs and a somewhat larger increase in ovarian cancer among younger patients was found. Our data suggest that preventive strategies to reduce the incidence of certain cancers (e.g., smoking cessation and prophylactic oophorectomy) and/or continued monitoring for SNBMs to increase the likelihood of early detection and treatment may be prudent in this population.     

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。     

乳腺癌放疗化疗时机顺序

放化疗联合治疗乳腺癌不仅涉及化疗方案、剂量、给药方式和放疗剂量、方式、方法等问题，两者时机顺序的合理安排更是获得最佳疗效的关键。现就有关研究进展作一综述。     

Adjuvant chemotherapy for early-stage breast cancer

Systemic chemotherapy is an integral component of the adjuvant treatment strategy for women who have early-stage breast cancer and accounts for significant improvements in breast cancer-specific mortality. Decisions regarding adjuvant therapy are increasingly complex with the advent of new therapeutic strategies, a growing body of literature on the molecular biology and natural history of breast cancer, and advances in therapeutic techniques and early detection. Ultimately, the risk-benefit calculus will continue to evolve in response to these advances and one hopes that clinicians will soon be able to tailor treatment recommendations to the biology of an individual cancer and the needs of the affected individual.