External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.     

乳腺癌保乳术后加速部分乳腺照射的研究进展

传统的乳腺癌保乳术后放疗是对全乳腺进行5周-6周的放疗.随着放射治疗技术的发展,加速部分乳腺照射可能会成为另一选择.该文就加速部分乳腺照射在乳腺癌治疗中的研究进展作一综述.     

Conservative surgery and irradiation (QUART) in the treatment of 243 stage I-II breast cancer patients.

From 1980 to 1987, 243 evaluable patients with pT1, pT2 (less than 3 centimeters in diameter), N0, M0, invasive breast cancer were treated with "quadrantectomy" with axillary dissection followed by electron beam radiation therapy (QUART) at the St. Bortolo Hospital, Vicenza. Stage II patients received adjuvant chemotherapy (CMF) if preperimenopausal or hormonotherapy (tamoxifen) if postmenopausal. The median follow-up was 54 months (26 to 116 months). The 4.5-year overall survival (OS) and disease-free survival (DFS) were respectively 91% and 85%; the 10-year actuarially estimated OS and DFS was 77%. Thirty-three patients relapsed, 11 of whom had local recurrence, and 23 developed distant metastases. A significantly longer OS and DFS were observed in stage I versus stage II (p = 0.0008) and in pT1 versus pT2 (p = 0.001) tumors. No difference was found regarding menopausal status and histotype. The local control of disease was very high (95.5%), with a significantly higher local recurrence rate in premenopausal women compared to postmenopausal (10/117 versus 1/126; p = 0.009). Tumor size did not influence the frequency of local recurrence. No major complications occurred but a significantly higher rate of reversible radiation-pneumonitis occurred in patients treated with higher energies of electrons (17 to 20 MeV) compared with lower (6 to 13 MeV) (33/177 versus 7/66; p less than 0.05). Cosmetic results were judged as excellent in 20%, satisfactory in 68%, unsatisfactory in 6% and not evaluable in 6% of cases. We conclude first, that small pT2 breast carcinomas may also be safely treated with QUART, second, that the electron beam is a radiotherapeutic technique able to produce a good cosmetic result and to assure a satisfactory local control and, finally, that the use of tamoxifen in postmenopausal stage II breast carcinomas is safe and easy to combine with radiotherapy in the conservative management of early breast cancer due to the lower toxic effects, compared to those observed in premenopausal women treated with chemotherapy.     

早期乳腺癌保乳术后部分乳腺照射的现状

乳腺癌的治疗经历了从大手术到小手术以尽量保存功能的过程。从全乳腺切除加腋窝淋巴结清扫术,到乳腺肿瘤区段切除加腋窝、前哨淋巴结活检术。手术的转变影响到放射治疗的应用。例如,一位早期乳腺癌患者,若行全乳腺切除和腋窝淋巴结清扫术,如果腋窝淋巴结阴性,就不需要进行放射治疗;若行乳腺肿瘤区段切除术,     

乳腺癌保乳术后加速部分乳腺照射的研究进展

传统的乳腺癌保乳术后放疗是对全乳腺进行5周-6周的放疗。随着放射治疗技术的发展,加速部分乳腺照射可能会成为另一选择。该文就加速部分乳腺照射在乳腺癌治疗中的研究进展作一综述。     

Breast conserving surgery and definitive irradiation for early stage breast cancer

Breast conserving surgery and postoperative breast radiotherapy were used to treat 219 cases of AJCC Stage I and II breast carcinoma at the Michael Reese and University of Chicago Hospitals. Most patients were treated with lumpectomy and axillary sampling followed by breast irradiation to a dose of 46 Gy followed by a boost dose of 14-16 Gy to the surgical bed. The 5-year actuarial local control is 92%. Follow-up is 1 to 10 years and the median follow-up is 36 months. Of the seven patients who recurred in the breast, three failed in the boost site and three failed adjacent to the boost site. The seventh patient recurred diffusely in the breast and skin. Four of the seven recurrences were in patients with positive surgical margins. The 5-year actuarial relapse-free survival is 80%. Factors which had an adverse affect on the cosmetic results were a scar length greater than 8 cm and a volume of resected breast tissue greater than 100 cm3. Treatment related complications were minor and infrequent. Breast conserving surgery followed by radiation therapy is effective in achieving local control with good to excellent cosmetic results.     

Patient involvement in surgery treatment decisions for breast cancer.

PURPOSE: High rates of mastectomy and marked regional variations have motivated lingering concerns about overtreatment and failure to involve women in treatment decisions. We examined the relationship between patient involvement in decision making and type of surgical treatment for women with breast cancer. METHODS: All women with ductal carcinoma-in-situ and a 20% random sample of women with invasive breast cancer aged 79 years and younger who were diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries were identified and surveyed shortly after receipt of surgical treatment (response rate, 77.4%; n = 1,844). RESULTS: Mean age was 60.1 years; 70.2% of the women were white, 18.0% were African American, and 11.8% were from other ethnic groups. Overall, 30.2% of women received mastectomy as initial treatment. Most women reported that they made the surgical decision (41.0%) or that the decision was shared (37.1%); 21.9% of patients reported that their surgeon made the decision with or without their input. Among white women, only 5.3% of patients whose surgeon made the decision received mastectomy compared with 16.8% of women who shared the decision and 27.0% of women who made the decision (P < .001, adjusted for clinical factors, predisposing factors, and number of surgeons visited). However, this association was not observed for African American women (Wald test 10.0, P = .041). CONCLUSION: Most women reported that they made or shared the decision about surgical treatment. More patient involvement in decision making was associated with greater use of mastectomy. Racial differences in the association of involvement with receipt of treatment suggest that the decision-making process varies by racial groups.     

Breast conservation surgery with irradiation in breast cancer

For the treatment of patients with early breast cancer, breast conservation surgery with irradiation is gaining world wide acceptance as opposed to more mutilating operations. In Japan, however, most surgeons and radiation oncologists are still unfamiliar with this technique. To achieve optimum functional and cosmetic results, understanding the philosophy and details of the technique is of primary importance. We propose a method of executing the procedures. Tumor excision with a tumor-free margin and breast irradiation with tangential fields are the essential part of the treatment. The entire breast should not receive more than 50 Gy. Limited axillary dissection is used for deciding the indications for chemotherapy, and it is necessary to obtain more than five nodes. Irradiation to the lymph nodes is optional.     

早期乳腺癌保乳手术后加速部分乳腺照射与全乳照射剂量学的比较

目的比较早期乳腺癌患者保乳手术后加速部分乳腺照射(APBI)与全乳照射(WBI)剂量学的差异。方法选取2013年1月至2013年12月间收治的26例保乳术后采用APBI治疗的乳腺癌患者作为观察组,另选取同期保乳术后采用WBI治疗的28例乳腺癌患者作为对照组。采用剂量体积直方图(DVH)比较两组患者剂量学差异,总结两组患者的短期疗效;比较观察组患者在有无图像指导下的位移差异。结果观察组患者的平均剂量(Dmean)、照射体积百分比(V103、V105、V110)和靶区剂量不均匀指数(IHI)均显著低于对照组,各项危及器官(OARS)照射剂量均显著低于对照组,且心脏和肺的照射体积也显著低于对照组,差异均有统计学意义(均P<0.05)。观察组患者美容满意率为96.2%(25/26),对照组患者为67.9%(19/28),两组间差异有统计学意义(P<0.05)。观察组患者在有无图像引导下的位移差异均有统计学意义(均P<0.05)。结论早期乳腺癌患者保乳手术后APBI照射剂量低于WBI,改善靶区剂量分布,降低心肺等组织高剂量受照体积,结合图像引导,可以增加准确性。     

Inflammatory breast cancer: integration of irradiation, surgery, and chemotherapy.

Between January 1983 and April 1987, 36 consecutive patients with nonmetastatic clinical (30 patients) or occult (6 patients) inflammatory breast cancer were treated with irradiation, mastectomy, and chemotherapy. In 29 patients, treatment consisted of preoperative once daily (16 patients) or twice daily (13 patients) irradiation with concurrent chemotherapy. In 27 (93%) of these 29 patients, this treatment was followed by mastectomy and additional chemotherapy. In 25 (86%) of these patients, major clinical response was attained, but an examination of the pathology of the operative specimen revealed complete tumor absence in only two patients (7%). The remaining seven patients underwent immediate mastectomy followed by once daily irradiation and chemotherapy. With a median follow-up of 30.4 months in all patients (59.2 months in surviving patients), the 5-year probability of relapse-free survival was 24% and of overall survival, 34%. Overall, the probability at 5 years of initial isolated local-regional tumor recurrence was 19%; in patients treated with once daily irradiation, the 5-year probability was 28%, whereas the probability was 8% with twice daily (accelerated) fractionated irradiation. Chemotherapy dose intensity did not appear to be adversely affected by the use of irradiation. The treatment approach described herein provides results comparable with those in other contemporary American series.     

Ten year results of conservative surgery and irradiation for stage I and II breast cancer.

Between 1977 and 1985, 697 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Reexcision of the primary was performed in 330 and residual tumor was identified in 57% of these patients. Margins of resection were assessed in 50% and 257 had final margins of resection that were negative. Four hundred eighty patients had negative axillary dissections and 217 had histologically positive axillary nodes. Median follow-up was 58 months. The 10-year actuarial survival for the entire group was 83% with an NED survival of 73%. The 10-year actuarial survival was 87% for clinical Stage I and 77% for clinical Stage II patients with an NED survival of 79% and 67%, respectively. Patients with histologically negative axillary nodes had a 10-year overall survival of 86% (NED 78%) compared to 74% (NED 66%) for patients with positive nodes. Sixty-one patients developed a recurrence in the treated breast and in seven of these it was associated with simultaneous distant metastases. The cumulative probability of an isolated breast recurrence was 6% at 5 years and 16% at 10 years. The overall breast recurrence rate (+/- distant metastasis) was 8% at 5 years and 18% at 10 years. Breast recurrence was unrelated to T size, clinical stage, or histologic nodal status. The addition of adjuvant chemotherapy significantly decreased the risk of an isolated breast recurrence both at 5 and 10 years; however, there was no significant impact on the overall risk of a breast recurrence. Complications of treatment included moderate arm edema (5%), symptomatic pneumonitis (less than 1%), rib fraction (1%), pericarditis (0%), and brachial plexopathy (less than 1%). Cosmesis was judged to be good to excellent in 93% of patients in 10 years. These results have been achieved in a series of patients who for the most part have been treated by contemporary standards, that is, pathologic assessment of the axilla in all patients, reexcision in 47%, and adjuvant chemotherapy in 77% of node positive patients. Assessment of resection margins, however, was not performed in all patients (50%) and further follow-up in the group of patients with margin assessment will provide long term information on breast recurrence rate in this group of patients.     

Partial breast irradiation as second conservative treatment for local breast cancer recurrence

PURPOSE: Mastectomy is the treatment of reference for local relapse after breast cancer (BC). The aim of this study was to document the feasibility and the results of associating lumpectomy with partial breast irradiation by interstitial brachytherapy (IB) as local treatment for an isolated ipsilateral BC local recurrence (LR). METHODS AND MATERIALS: Between 1975 and 1996 at Marseille and Nice Cancer Institutes, 4026 patients received lumpectomy and radiotherapy (RT) (50-80 Gy) for a localized breast cancer of which 473 presented a LR. Among these patients, 69 (14.6%) received a second lumpectomy followed by IB, which delivered 30 Gy (Nice, n = 24) or 45-50 Gy (Marseille, n = 45) with 3 to 8 (192)Ir wires in 1 or 2 planes on the 85% isodose. RESULTS: Median age at LR was 58.2 years, median follow-up since primary BC was 10 years, and median follow-up after the second conservative treatment was 50.2 months (range, 2-139 months). Immediate tolerance was good in all cases. Grade 2 to 3 long-term complications (LTC) according to IB dose were 0%, 28%, and 32%, respectively, for 30 Gy, 45 to 46 Gy, and 50 Gy (p = 0.01). Grade 2 to 3 LTC according to total dose were 4% and 30%, respectively, for total doses (initial RT plus IB) < or = 100 Gy or >100 Gy (p = 0.008). Logistic regression showed that the only factor associated with Grade 2 to 3 complications was higher IB doses (p = 0.01). We noted 11 second LRs (LR2), 10 distant metastases (DM), and 5 specific deaths. LR2 occurred either in the tumor bed (50.8%) or close to the tumor bed (34.3%) or in another quadrant (14.9%). Kaplan-Meier 5-year freedom from (FF) LR2 (FFLR2), FFDM, and DFS were 77.4%, 86.7%, and 68.9%, respectively. Overall 5-year survival (OS) was 91.8%. Univariate analysis showed the following factors associated with a higher FFLR2: (1) number of wires used for IB (3-4 vs. 5-8 wires, p = 0.006), (2) IB doses (30-45 Gy vs. 46-60 Gy, p = 0.05), (3) number of planes (1 vs. 2, p = 0.05), (4) interval between primary breast cancer and LR (< 36 months vs. > or =36 months, p = 0.06). Multivariate analysis showed two factors associated with better local control: (1) number of wires (5-8 wires, p = 0.013) and (2) interval between primary breast cancer and LR > or =36 months (p = 0.039). The multivariate analysis showed two factors associated with better FFDM: (1) absence of initial axilla involvement (p = 0.019) and (2) relapse in a different location (p = 0.04). These two factors were also associated with a higher OS. CONCLUSION: Our experience showed that second conservative treatments for local relapse were feasible and gave results comparable to standard mastectomy. We recommend delivering IB doses of at least 46 Gy in 2 planes when initial radiotherapy delivered 50 Gy. The study gives enough information to encourage a Phase III trial that compares radical mastectomy to conservative procedures for localized breast cancer recurrences.     

早期乳腺癌保乳术后加速部分乳腺放疗相关研究进展

早期乳腺癌保乳术后全乳放疗是目前标准的治疗方式,可有效降低复发率。由于大多数复发发生在肿瘤切除腔的附近,加速部分乳腺照射(APBI)作为一种只针对原发病灶周围有限体积的组织进行大分割照射的特殊放疗方式,引起了越来越多的关注。近年来,多项前瞻性的随机对照研究证实了其安全性及有效性,对特定的低危保乳术后患者是可行的选择。与全乳放疗相比,APBI缩短了治疗时间,降低了治疗成本,改善了美容效果。同时越来越多的APBI治疗技术被开发出来,增强了患者的可及性,对于部分早期乳腺癌保乳术后患者而言有其独特的优势。尽管如此,APBI技术在疗效及不良反应上存在不同,需区别看待。本文主要就APBI的各种治疗技术、国内外研究进展以及适用人群进行综述,提出尚待解决的问题,展望其发展前景,为临床应用提供参考。     

Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer.

Four hundred consecutive patients aged under 70 years diagnosed with a clinical T1 or T2 breast cancer were randomised to receive post-operative radiotherapy (n = 208) or not (n = 192), and monitored to record all local recurrences, distant recurrences and deaths for up to 20 years (median 13.7 years). All patients were treated by wide local excision and adjuvant therapy [estrogen receptor (ER) positive: tamoxifen; ER negative: CMF chemotherapy]. Kaplan-Meier and log-rank test methods were used to estimate and compare survival and recurrence. The 20-year Kaplan-Meier rates for local breast recurrence were 28.6% [95% confidence interval (CI) 19.6% to 37.6%] for radiotherapy and 49.8% (95% CI 40.8% to 58.9%). There was no significant difference between the two groups with regard to disease-free or overall survival. The hazard ratio for death among women who received radiation, as compared with those that did not, was 0.91 (95% CI 0.64-1.28; P = 0.59). Therefore, post-operative radiotherapy produced a clear-cut reduction in locoregional recurrence 0.45 (0.31-0.64; P = 0.0001), but did not influence the incidence of distant metastases or time of death. However, of the 119 patients who had a local recurrence, 51 (42.8%) had a distant recurrence, whereas of the 281 without local recurrence only 59 (21%) ever had a distant recurrence. A Cox's regression analysis with local recurrence as a time-dependent variable showed a risk ratio of 5.28 (P < 0.0001). This strong relationship is dependent on the intensity of post-treatment follow-up and investigation.     

乳腺癌保乳术后瘤床补量照射的一种新方法

目的通过保乳术后外科银夹和术后瘢痕的位置,建立一种新的瘤床补量照射方法。方法以早期乳腺癌保乳术后26例患者为研究对象,所有病例都采用外科银夹标记瘤床内外上下切缘（未标记后切缘）。在行CT模拟定位前用铅丝标记术后瘢痕,CT扫描后勾画乳头、银夹和术后瘢痕。虚拟定位布野如下：首先在机架0°时,将射野中心放在标记切缘银夹中心,然后向内切或外切方向旋转机架,使乳腺内银夹在射野中投影满足至少3个以上银夹共线,然后机架转至正交位,调整照射野包括银夹和术后瘢痕。结果85%（88/103）银夹深达胸大肌和肋骨表面。银夹在射野中投影类型14例为3个银夹共线,其余12例为4个银夹共线。瘤床深度平均值为4．37 cm,95%可信区间为3．98～4．96 cm,瘤床深度范围为2．40～6．20 cm,77%（20/26）病例的瘤床深度＜5 cm。结论这种补量照射方法是基于外科银夹以达到精确照射三维瘤床。     

Long-term results of breast cancer irradiation treatment with low-dose-rate external irradiation

PURPOSE: The aim of this study was to assess beam therapy with low-dose-rate (LDR) external irradiation in a group of patients with breast cancer. METHODS AND MATERIALS: This trial compared, from 1986 to 1989, patients with advanced breast cancer treated either by conventional fractionation or low-dose-rate (LDR) external radiotherapy (dose-rate 15 mGy/min, 5 sessions of 9 Gy delivered on 5 consecutive days). RESULTS: A total of 21 patients were included in the fractionated therapy arm. At follow-up 15 years after treatment, 7 local recurrences had occurred, 3 patients had died of cancer, 18 patients were alive, 10 were without evidence of disease, and 6 had evidence of disease. A total of 22 patients had been included in the LDR arm of the study. Of these, 11 had received a dose of 45 Gy; thereafter, in view of severe local reactions, the dose was reduced to 35 Gy. There was no local recurrence in patients who had received 45 Gy, although there were 2 local recurrences among the 11 patients after 35 Gy. The sequelae were severe in patients who received 45 Gy but were comparable to those observed in patients treated by fractionated radiotherapy who received 35 Gy. The higher efficacy of tumor control in patients treated by LDR irradiation as well as the lower tolerance of normal tissue are probably related to the lack of repopulation. CONCLUSION: Although the patient numbers in this study are limited, based on our study results we conclude that the data for LDR irradiation are encouraging and that further investigation is warranted.     

Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer

At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.     

Regional nodal irradiation in the conservative treatment of breast cancer

At this institution conservative treatment of breast cancer was begun in the 1960's. The following analysis represents our experience through 1984 with specific reference to the management of the regional lymph nodes. A total of 432 patients with clinical stage I and II breast cancer were treated between 1962 and 1984 with lumpectomy and radiation therapy. The breast was treated with tangential fields to a median dose of 4800 cGy and electron conedown to a total tumor bed dose of 6400 cGy. Axillary dissection was not routinely performed, particularly in the earlier years. More recently, axillary dissection has been used with increasing frequency if it was felt that the results of the dissection would influence systemic treatment. One hundred eighty-seven patients (43%) underwent axillary dissection (30% pathologically positive) and routinely received regional nodal irradiation (median dose 4600 cGy) to the internal mammary and supraclavicular lymph nodes. Two hundred forty-five patients (57%) did not undergo axillary dissection and routinely received regional nodal irradiation to the internal mammary, supraclavicular, and entire axillary regions to a total median dose of 4600 cGy. As of May 1989 with a median follow-up of 7.5 years, there have been a total of 12 nodal failures for an actuarial nodal control rate of 97% at 5 years and 96% at 10 years. The actuarial 5-year regional nodal control rate was the same for both the group of patients receiving regional RT alone without axillary dissection and the group of patients receiving axillary dissection and supraclavicular/internal mammary radiation. There has been minimal morbidity associated with this treatment policy. We conclude that regional nodal irradiation as described above, with or without axillary dissection, results in a high rate of regional nodal control and minimal treatment morbidity in patients undergoing conservative treatment of early stage breast cancer.