乳腺癌保乳术后放射治疗进展

保留乳房治疗现已成为欧美国家早期乳腺癌治疗的首选，而且在国内也得到了医患双方的广泛认同，保留乳房治疗患者所占比例迅速增加。放射治疗是乳腺癌保留乳房治疗的重要组成部分。它不仅明显提高局部／区域肿瘤控制，而且提高患者的远期生存率。随着乳腺癌保乳手术模式的改变、保留乳房治疗（BCT）后乳房内复发模式的确定及放射治疗技术自身的发展，乳腺癌保乳术后放射治疗的技术和内容也在不断发展和变化。本文就其中的某些方面予以综述。     

Primary radiation therapy for locally advanced breast cancer

The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%. It is concluded that high-dose radiation therapy without mastectomy is an effective means of controlling local-regional tumor in patients with locally advanced breast cancer.     

Adjuvant radiation therapy following mastectomy for breast cancer

Many randomized clinical trials have been performed to address the effectiveness of postmastectomy radiation therapy (PMRT) to regional lymph nodes with or without chest wall irradiation. Although these studies have confirmed the usefulness of RT to reduce loco-regional recurrence, the benefit of postoperative RT for survival remains controversial. Recent prospective trials of PMRT in combination with systemic chemotherapy clearly demonstrated the benefit of this combined adjuvant therapy for both locoregional recurrence and survival outcomes. Based upon this new evidence, guidelines and recommendations for PMRT in the management of breast cancer have been proposed by the American Society of Clinical Oncology and by the International Consensus Panel at the International Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen. PMRT is recognized as a standard adjuvant treatment for patients with more than 4 positive axillary nodes in these guidelines and recommendations. This re-appraisal of PMRT has not attracted much attention in Japan so far. Clinical studies are needed to determine how to best incorporate PMRT in the multimodal treatment of node-positive breast cancer.     

Radical radiation therapy of breast cancer

The 5 year results of radical radiation therapy in operable, infiltrating breast cancer (T1, T2, T3; NO, N1a, N1b) in 177 patients are presented. The treatment protocol included a pre-radiotherapy tumorectomy for T1 and certain T2 tumors (those less than 3cm diameter). Patients with larger tumors were treated by radiotherapy alone. The treatment technique incorporated both conventional fractionated radiotherapy (60 Co and electrons) and endocurietherapy (192 Ir). At 5 years, the uncorrected, disease-free survival rates were 84 % for T1, 79% for T2 and 56% for T3: loco-regional persistent or recurrent disease was seen in 4.5 % of patients with Tl disease, 7.5 % of those with T2, and 23 % of T3 patients; 16 mastectomies had been performed. Of the patients with T1 and T2 disease, 95 % had retained their breast and the esthetic result was judged to be good in 75 %. We recommend this technique of radical radiotherapy in early breast cancer because of this high rate of tumor control, associated with a low rate of normal tissue damage and survival figures comparable to those achieved by radical surgery.     

早期乳腺癌放射治疗进展

放射治疗在早期乳腺癌的综合治疗中具有重要地位。在早期浸润性乳腺癌乳房保留治疗已成熟的基础上，近年的临床研究着眼于对乳房保留治疗的标准模式的挑战，包括全乳照射后瘤床加量的意义，是否有低危复发患者可以接受单纯手术以及部分乳腺照射的可行性等。对于局部复发高危患者进行乳房切除术后胸壁和区域淋巴结的放射治疗可以降低2／3的局部和区域的复发率，但是目前仍然只有少数研究证实术后放疗提高了生存率，尤其关于中等复发危险的患者术后放疗是否有价值尚存在较多争议。本文将对上述进展和争议作一综述。     

Long-term results of neoadjuvant radiation therapy for breast cancer

Our aim was to determine the long-term outcome and the possible role of neoadjuvant (preoperative) radiation therapy for breast cancers unsuitable for primary conservative surgery. From 1977 to 1992, 75 unifocal non-inflammatory and non-metastatic T2 and T3 breast cancers were treated in our department. All these patients underwent initial radiotherapy, followed by secondary limited surgery. A population of 74 patients, aged from 32 to 82 years (median 56 years), presenting 49 T2 and 26 T3 tumors, was studied. Seventy-two patients (96%) underwent secondary tumorectomy and three patients (4%) reduction mammaplasty. The secondary tumorectomy was followed by a postoperative boost. There were nine recurrences, treated by mastectomy in eight cases and by tumorectomy in one case. Twenty-five patients showed secondary dissemination. Forty-seven patients are still alive and free of disease. The cosmetic results were considered excellent or satisfactory in 71 cases. Under good conditions, preoperative radiotherapy (as well as preoperative chemotherapy) allows the possibility of conservative surgery for cancers of more than 3 cm. The choice between the two modalities depends on the patient's condition and on a precise analysis of all prognostic factors that would justify the need for systemic treatment.     

Lactation after breast conserving therapy, including radiation therapy, for early breast cancer

Two patients who underwent breast conservation including radiotherapy for early breast carcinoma are described and who subsequently delivered healthy newborn infants. One of the two patients lactated from both the irradiated and the non-irradiated breast; whereas the other patient did not lactate from the irradiated side. The treatment and implications are discussed.     

The roles and controversies of radiation therapy in breast conserving therapy for breast cancer

Breast conserving therapy (BCT) is defined as a combination of conservative surgery for resection of the primary tumor, followed by radiation therapy (RT) for the eradication of residual microscopic disease in the breast. At NIH Consensus Development Conference in 1990, BCT was recognized as the preferred treatment for the majority of women with Stage I and II breast cancer. RT is a potent locoregional treament and its role in BCT in reducing local recurrence is already established. On the other hand, the influence of RT on survival outcome has not yet been closely demonstrated so far. RT appears to be useful as neoadjuvant therapy, and also as exclusive local treatment for patients achieving complete regression (CR) after neoadjuvant chemotherapy. The other possible role of RT is to use it as an alternative to axillary dissection in patients with clinically uninvolved nodes. The question of the appropriateness of using RT in all BCT cases is raised. Since the subgroup of patients who would not deserve any benefit by RT has not yet identified, RT should be delivered as standard treatment following breast conserving surgery for early stage breast cancer.     

Cosmetic results following primary radiation therapy for early breast cancer

In order to assess the cosmetic results of treatment, the results in 239 patients with early breast cancer treated by primary radiation treatment without adjuvant chemotherapy were reviewed. Four patients had bilateral cancers, making a total of 243 breasts available for analysis. Follow-up ranged from 24 to 78 months with a median of 33 months. The parameters measured were breast edema, retraction, telangiectasia, arm edema, and the overall cosmetic appearance. The cosmetic results declined over the first 3 years after treatment, but then stabilized. At 5 years, the overall cosmetic results were judged by physicians as excellent in 77%, good in 9%, fair in 9%, and poor in 5%. A fair or poor cosmetic result was highly correlated with the development of moderate or severe breast retraction. Telangiectasia was uncommonly the only cause of a fair or poor cosmetic result. Breast and arm edema were rarely noted to be significant, but were more common in patients who underwent axillary dissection. In 210 cases, a supplementary boost dose of radiation was delivered to the primary tumor area, and in 33 cases a boost was not used. This boost consisted of an interstitial iridium-192 implant in 204 cases and either high-energy photons or electrons in the remainder. At 4 years, no patient treated without a boost had a fair or poor result compared with 22% who received a boost (P = 0.13). The conclusion is that, in general, primary radiation treatment provides highly satisfactory cosmetic results for patients with early breast cancer.     

放疗与药物联合治疗乳腺癌的研究进展

综合治疗是目前提倡的乳腺癌治疗策略,而放疗在乳腺癌综合治疗中具有重要地位。为探索疗效更好、毒副反应更低的综合治疗方案,本文概述放疗与药物联合应用治疗乳腺癌的现状和进展,重点阐述放疗与化疗、内分泌治疗、靶向治疗等药物联合治疗的研究现状与要点。     

Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery

AimsTo evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery.Materials and methodsIn total, 539 patients with pTis–pT1–pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons.ResultsAt the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (±0.5% standard error) and 2.1% (±0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity.ConclusionThis type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis.     

Primary radiation therapy for stage I and II breast cancer

In 1987 there were estimated to be approximately 130,000 new cases of breast cancer diagnosed in the United States. Presently, about 20-30,000 of these cases are treated with primary radiotherapy, although many more of the 90,000 stage I and II breast cancer cases are eligible for this form of treatment. Appropriate selection must be employed, including the size and site of the primary tumor, the size of the breast, the potential for multifocal disease, and the age of the patient. When proper selection is used, primary radiotherapy for stage I and II disease yields equivalent overall survival and NED survival when compared to traditional mastectomy. The benefit is preservation of the breast with good to excellent cosmesis in the vast majority of patients.     

Preliminary results of quadrantectomy and radiation therapy for breast cancer

Between November 1987 and December 1992, a total of 200 breast carcinomas in 199 patients were treated by definitive radiation therapy following quadrantectomy and level III axillary dissection. One patient with simultaneous bilateral breast cancers was excluded and 198 patients with breast cancer were enrolled in this study. There were 9 Stage 0, 117 Stage I and 72 Stage II tumors by the UICC tumor classification system (1987). Histological examination revealed that 9 tumors were non-invasive carcinomas and 189 were invasive carcinomas. For radiation therapy, a total of 50 Gy was delivered to the ipsilateral breast using⁶⁰Co γ rays. In three cases with level III lymph node involvement, the ipsilateral supraclavicular and parasternal regions were also irradiated. Boost irradiation was given to 8 of 12 margin-positive patients, and 2 of 24 patients in whom tumor cells were present within 5 mm from the margin. We used a CT simulator for the treatment planning of radiation therapy in 196 tumors. During follow-up for 16-77 months (median: 35 months), 2 patients died of unrelated causes and 6 developed distant metastasis (4 to bone and 2 to lung). Local recurrence was noted in 1 patient. Acute reactions to radiation therapy included moist desquamation involving the tip of the breast and the axilla in 14 and 5 patients, respectively, as well as bright erythema in 7 patients. Late reactions included arm edema in 12 patients, patchy depigmentation at the tip of the breast in 5 patients, moderate telangiectasia in 1 patient, and symptomatic radiation pneumonitis in 1 patient. The actuarial overall survival, cause-specific survival, disease-free survival, and relapse-free survival rates at 5 years were97.2%, 100%, 93.5%, and 93.0%, respectively. This excellent locoregional control, together with a highly acceptable toxicity strongly suggests the usefulness of quadrantectomy and radiation therapy for Japanese women with breast cancer. The possible indications include clinical Stage 0 and, I breast cancer, and clinical Stage II cancer in patients with relatively large breasts and with the primary tumor not located close to the nipple.     

Primary radiation therapy for early breast cancer: The experience at the joint center for radiation therapy

The results of primary radiation therapy in 176 consecutive patients with clinical Stage I and II carcinoma of the breast were reviewed. Median follow-up time was 47 months. The overall breast relapse rate was 7%. Patients undergoing interstitial implantation had a significantly lower breast relapse rate (1%) than patients not undergoing implantation (11 %). Breast relapse was more common in patients undergoing incisional or needle biopsy (17 %), compared to patients treated after excisional biopsy (5 %). In patients undergoing excisional biopsy, but not interstitial implantation, breast relapse was related to external beam dose. Twelve percent of the patients who received less than 1600 ret dose relapsed in the breast, compared to none of the 19 patients who received more than 1700 ret dose. These results imply that supplemental irradiation to the primary tumor area is required following excisional biopsy of a primary breast cancer when 4500–5000 rad is delivered to the entire breast.     

Genetic predictors of long-term toxicities after radiation therapy for breast cancer

Telangiectasia and subcutaneous fibrosis are the most common late dermatologic side effects observed in response to radiation treatment. Radiotherapy acts on cancer cells largely due to the generation of reactive oxygen species (ROS). ROS also induce normal tissue toxicities. Therefore, we investigated if genetic variation in oxidative stress-related enzymes confers increased susceptibility to late skin complications. Women who received radiotherapy following lumpectomy for breast cancer were followed prospectively for late tissue side effects after initial treatment. Final analysis included 390 patients. Polymorphisms in genes involved in oxidative stress-related mechanisms (GSTA1, GSTM1, GSTT1, GSTP1, MPO, MnSOD, eNOS, CAT) were determined from blood samples by MALDI-TOF. The associations between telangiectasia and genotypes were evaluated by multivariate unconditional logistic regression models. Patients with variant GSTA1 genotypes were at significantly increased risk of telangiectasia (OR 1.86, 95% CI 1.11-3.11). Reduced odds ratios of telangiectasia were noted for women with lower-activity eNOS genotype (OR 0.58, 95% CI 0.36-0.93). Genotype effects were modified by follow-up time, with the highest risk observed after 4 years of radiotherapy for gene polymorphisms in ROS-neutralizing enzymes. Decreased risk with eNOS polymorphisms was significant only among women with less than 4 years of follow-up. All other risk estimates were nonsignificant. Late effects of radiation therapy on skin appear to be modified by variants in genes related to protection from oxidative stress. The application of genomics to outcomes following radiation therapy holds the promise of radiation dose adjustment to improve both cosmetic outcomes and quality of life for breast cancer patients.     

早期乳腺癌保乳术后放射治疗进展

乳腺癌的研究一直是女性肿瘤研究中的热点.近年来随着放疗技术的发展及放疗设备的更新,早期乳腺癌术后放疗有了突飞猛进的发展.本文就保乳术后乳腺癌患者在不同照射方式、不同放疗技术、不同分割剂量及不同类型射线的运用等方面做一综述.