Late breast recurrence after lumpectomy and irradiation

For 276 patients with early breast cancer followed from 10-21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were "late failures," with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T1 than for T2 tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 year, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer. We do not consider the phenomenon of late recurrence to lend support to a policy of primary mastectomy, just as the existence of contralateral breast cancer does not justify routine "prophylactic" contralateral mastectomy.     

Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence: the potential role of partial breast irradiation

Mastectomy is the current standard of care for in-breast local recurrence of breast carcinoma. The objective of the current study was to critically review the rationale for and the theoretic and actual risks and benefits of repeat breast-conserving surgery followed by partial breast irradiation (PBI) for in-breast local recurrence of breast carcinoma. The main outcomes of interest were local control and survival after in-breast local recurrence and side effects, complications, and cosmesis after reirradiation of the breast. The risk of local recurrence was not found to be eliminated with mastectomy; approximately 2-32% of patients treated with mastectomy develop a chest wall recurrence. The interpretation of local control rates in evaluating repeat breast-conserving surgery studies is difficult because of the lack of information regarding preoperative diagnostic mammography to rule out concurrent multicentric disease and microscopic margin status after surgery. Rates of subsequent local recurrence in these studies appeared to be between 19-50%, similar to reported rates of in-breast local recurrence in patients with a first diagnosis of breast carcinoma who were treated with conservative surgery without irradiation. Early follow-up studies of breast reirradiation suggest that catheter-based interstitial brachytherapy and standard external beam radiation therapy can be delivered to the breast more than once without significant side effects in most patients and with acceptable cosmesis in some patients. Mastectomy may not be necessary in all patients with an in-breast local recurrence of breast carcinoma. Recent advances in conformal radiation delivery and single-center published reports concerning repeat breast-conserving therapy support well designed prospective trials to formally test this hypothesis.     

Repeat lumpectomy for patients with ipsilateral breast tumor recurrence after breast-conserving surgery. Preliminary results

In this study, we assessed the appropriateness of conducting repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) based on the characteristics of recurrence after primary breast conserving surgery (BCS). Of 41 patients who had developed IBTR from October 1986 to June 2000 at our institute, 11 underwent mastectomy of the remaining breast and 30 underwent repeat lumpectomy. The 5-year overall survival rate at a median follow-up of 43 months after salvage surgery was 90.9% for the mastectomy group and 90.0% for the lumpectomy group. The 5-year distant disease-free survival rate was 70.1% for the mastectomy group and 83.0% for the lumpectomy group. The survival rates were remarkably high in both treatment groups, with no significant difference between them. IBTRs in the majority of our patients were small lesions less than 1 cm in diameter. They did not feature lymphatic invasion and had low histological grade. Compared with that of primary lesions, the malignancy of recurrent tumors was not increased in many patients. In contrast to these preferable features, 9 of 30 patients who underwent repeat lumpectomy developed second local relapse within 3 years after salvage operation. Young age (相似文献   

Factors predicting in-breast tumor recurrence after breast-conserving surgery

Purpose: The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. Methods: A total of 335 consecutive patients with 346 invasive and in situ breast cancers were treated with breast conserving therapy. Univariate and multivariate statistical analysis were performed and survival rates were calculated and analyzed using the Kaplan–Meier method. Results: With a median follow-up period of 70.6 months 14 patients (4%) developed an IBTR. Overall survival and the disease-free 8-year actuarial survival of patients were 95% and 93%, respectively. The overall survival of patients with tumour recurrence on any site was significantly shorter than of those without recurrence (64% versus 85% after 8 years of follow-up; P < 0.0001). Similarly, overall survival was significantly reduced in patients with distant metastases compared to all others without distant disease (88% versus 40% after 8 years; P < 0.0001). In contrast, overall survival of patients who experienced IBTR did not differ significantly from the group of patients who never developed IBTR (87% versus 70% after 8 years of follow-up). By univariate analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS and DCIS, the absence of estrogene and progesterone receptor status, as well as R1-status, were significant predictors of IBTR. By multivariate analysis, only R1-status (P < 0.002) and the presence of LCIS around the invasive tumour (P < 0.03) remained as significant factors predicting IBTR. Conclusions: Concomitant lobular carcinomas in situ, as well as R1 surgical status are independent significant risk factors for in breast tumor recurrence after breast conserving therapy.     

Arm edema after lumpectomy and breast irradiation

Ipsilateral arm edema can be a troublesome adverse sequel of breast conservation therapy. We carried out a prospective study of arm edema in every patient (265) seen during a 6-month period for follow-up after radiotherapy postlumpectomy for unilateral primary breast cancer. One hundred eighty-one (181) women (68.3%) had an axillary dissection. All had radiotherapy to the breast via parallel opposed tangential beams. Only eight (3%) had additional separate portals for irradiation of nodal areas. Adjuvant systemic therapy consisted of tamoxifen alone in 127 patients (47.9%) and chemotherapy with or without tamoxifen in 60 (22.6%). Ipsilateral arm edema developed in 19 patients (7.2%). Edema was mild (1+) in 16 patients, and moderate in 3 (2+). Multivariate analysis revealed that the risk of arm edema was significantly increased in heavier women (p = 0.0016), women who had an axillary dissection (p = 0.0446), and women who received tamoxifen (p = 0.0385).     

High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6–9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1–7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.     

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR

Objectives

There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown.

Methods

We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed.

Results

The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival.

Conclusion

Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.     

Factors affecting recurrence in lumpectomy without irradiation for breast cancer.

Between 1980 and 1988, 122 women with operable invasive breast cancers underwent wide excision and axillary dissection without subsequent irradiation. During the follow-up period of 1 to 8 years (median, 4 years), recurrences were observed in 23 patients (19%), 22 occurring in the breast and one in the axilla. This is a significant rate of recurrence and supports the need for breast irradiation after conservative surgery. The incidence of recurrence in the breast did not appear to be related to the presence or absence of axillary nodal metastasis. No recurrences were noted in 20 patients whose primary tumors were smaller than 1 cm. The incidence of recurrence was directly correlated to the increasing size of the tumor, but it also appeared to decrease with advancing age. In 31 patients over 70 years of age, only one (3%) recurrence was observed. If these early findings are confirmed, it is likely that patients with tumors smaller than 1 cm or patients over 70 years of age may be spared breast irradiation after wide excision.     

Image guidance in external beam accelerated partial breast irradiation: comparison of surrogates for the lumpectomy cavity

PURPOSE: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. METHODS AND MATERIALS: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs (DeltaCOM(Bone), DeltaCOM(Clips), and DeltaCOM(Surface)) were determined. Smaller DeltaCOMs were interpreted as better localizations. Correlation coefficients were calculated for DeltaCOM vs. several variables. RESULTS: The DeltaCOM(Bone) (mean, 7 +/- 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization (DeltaCOM(Clips) < DeltaCOM(Bone)) in 25 of 27 cases. Breast surface matching improved cavity localization (DeltaCOM(Surface) < DeltaCOM(Bone)) in 19 of 27 cases. Mean improvements (DeltaCOM(Bone) - DeltaCOM(Clips or Surface)) were 4 +/- 3 and 2 +/- 4 mm, respectively. In terms of percentage of improvement ([DeltaCOM(Bone) - DeltaCOM(Clips or Surface)]/DeltaCOM(Bone)), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. CONCLUSIONS: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.     

Cosmetic results in early breast cancer treated with lumpectomy, peri-operative interstitial irradiation, and external beam radiation

Patients with operable breast cancer were treated at the University of Kansas Medical Center with lumpectomy, peri-operative interstitial Iridium, and external beam radiotherapy, and concomitant adjuvant chemotherapy in a majority of node positive cases. Examination of the cosmetic results in 85 breasts followed for at least 2 years, at a median of 41 months revealed 20% to be excellent, 44% to be very good, 24% good, 9% fair, and 4% to have poor results. In this paper cosmesis is analyzed with reference to the size of the primary, its location, age of the patient, whether the patient received adjuvant chemotherapy, and whether the regional nodes were treated. In this group of patients, the size and the site of the primary, patient's age, and whether adjuvant chemotherapy was administered or not, did not adversely affect the aesthetic outcome. Treatment of the regional nodes gave a worse mean cosmetic score compared to the group in whom only the breast was treated (37.51 vs. 58.98 respectively, p less than 0.001). Among the 11 patients with fair/poor cosmesis, all had regional nodal treatment, 7/11 had inner quadrant lesions, and 7/11 had lesions greater than T1. Further follow-up and accrual would be needed to confirm our results and affirm if other factors would change.     

Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings.

The latest findings from the NSABP B-06 trial on ipsilateral breast tumor recurrence (IBTR) continue to demonstrate that through 9 years of follow-up more patients treated with radiation remained IBTR free as compared to those receiving no radiation (P less than 0.001), regardless of age, nodal status, or tumor size. There is no significant difference in distant disease-free survival (DDFS) or survival between the two lumpectomy groups despite the highly significant difference in their probability of remaining IBTR free. A recent analysis shows that when a patient is diagnosed with an IBTR, the risk of distant metastatic disease increases, indicating that an IBTR is a marker for, not a cause of, distant metastatic disease. An IBTR indicates a greater risk for distant disease when the primary tumor was removed. Mastectomy or breast irradiation following lumpectomy eliminates or reduces the opportunity for identifying a marker of risk for distant disease, thus emphasizing the importance of an IBTR beyond the need for its removal. Since an IBTR is associated with a relative risk of 3.41 for the development of distant metastatic disease, systemic therapy subsequent to an IBTR should be considered. Evidence presented from recent NSABP studies indicates the value of systemic therapy for lowering the incidence of IBTR following lumpectomy and breast irradiation.     

Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06.

Ipsilateral breast tumor recurrence (IBTR) occurred in 42 of 488 (9%) pathologically evaluable patients enrolled in NSABP protocol B-06 with a mean potential follow-up of 103 months (range 68-161 months) following treatment for Stage I and II invasive breast cancer by lumpectomy and local breast irradiation (LXRT). IBTR were observed at or close to the same quadrant as the index cancers and their histologic types and nuclear grades were similar if not identical in 95 and 93%, respectively. This information confirms our earlier findings which indicated that multicentricity is of little or no clinical significance in the treatment of breast cancer by LXRT; breast cancers rarely if ever change their biologic potential once clinically detected; and lastly, most if not all IBTR represent residual cancer. Cox regression analyses revealed only a patient age less than 35 years to be significantly related to IBTR. No relationship between IBTR and so-called extensive intraductal component (EIC) or 31 other pathologic features of the index cancers was found. Overall survival was significantly related to nodal status (P = 0.01), nuclear grade (P = less than 0.001) histologic tumor type (P = 0.01) and IBTR (P = less than 0.001). This latter was considered as an indicator rather than instigator of distant disease and reduced survival since the latter is no different in patients treated by LXRT, lumpectomy alone after which IBTR is much more frequent, or mastectomy, which precludes its expression. We conclude that there are as yet no viable markers which would contraindicate treating patients with breast cancer by LXRT.     

乳腺癌保守手术治疗后同侧局部复发危险因素的探讨

目的 探讨临床、病理因素及辅助治疗对乳腺癌保守手术合并放疗后同侧局部复发的影响。方法 应用Kaplan-Meier方法和Cox比例风险模型对126例保乳术合并放疗的早期乳腺癌患者进行回顾性分析。结果 多因素条件下56岁以上乳腺癌患者保乳手术合并放疗后同侧局部复发的风险比为2.17,EIC阳性的风险比为3.46,病灶切缘不净为1.68,无辅助TAM治疗组的风险比为1.52。结论 年龄、EIC及切缘情况对保乳术合并放疗后同侧局部复发有重要的影响,同时辅助TAM治疗可以减少局部复发的风险。     

Video surface image guidance for external beam partial breast irradiation

ObjectiveAccelerated partial breast irradiation is an emerging treatment option for early stage breast cancer. With accelerated partial breast irradiation, patient setup, and target registration accuracy is vital. The current study compared various methods for isocenter placement accuracy.Methods and MaterialsTwenty-three patients treated on an institutional-approved partial breast irradiation protocol were monitored at each treatment fraction. All patients included in this study underwent clip placement at the time of surgery. Patients underwent computed tomographic simulation and surface contours were used to reconstruct a reference surface map. At the treatment machine, patients were initially positioned by laser alignment to tattoos. Orthogonal kilovoltage imaging of the chest wall, followed by video surface mapping of the breast, was performed. This video surface map was matched to the reference surface map to adjust the couch position. Verification orthogonal chest wall imaging and video surface mapping was again performed. The accuracy of setup by laser, orthogonal imaging of the chest wall, and surface alignment was retrospectively compared using the centroid clip position as the reference standard. The impact of setup error by surface alignment and by orthogonal kilovoltage imaging on planning target volume coverage was then calculated.ResultsLaser-based positioning resulted in a residual setup error of 3.9 ± 3.7 mm, 4.6 ± 3.9 mm, and 4.3 ± 4.5 mm in the posterior-anterior (P-A), inferior-superior (I-S), and left-right (L-R) directions, respectively, using clips as the reference standard. Setup based on bony anatomy with orthogonal imaging resulted in residual setup error of 3.2 ± 2.9 (P-A), 4.2 ± 3.5 (I-S), and 4.7 ± 5.3 mm (L-R). Setup with video surface mapping resulted in a residual setup error of 1.9 ± 2.2, 1.8 ± 1.9, and 1.8 ± 2.1 mm in the P-A, I-S, and L-R directions, respectively. Vector spatial deviation was 8.8 ± 4.2, 8.3 ± 3.8, and 4.0 ± 2.3 mm with laser, chest wall on board imaging, and video surface mapping based setup, respectively. Setup by video surface mapping resulted in improved dosimetric coverage of the planning target volume when compared with orthogonal imaging of the chest wall (V100 96.0% ± 0.1% vs 89.3% ± 0.2%; V95 99.7% ± 0.01% vs 98.6% ± 0.01%, P < .05).ConclusionsVideo surface mapping of the breast is a more accurate method for isocenter placement in comparison to conventional laser-based alignment or orthogonal kilovoltage imaging of the chest wall.     

Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer

BACKGROUND: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy that reduces the local recurrence of breast cancer. Because an optimal fractionation schedule (radiation dose given in a specified number of fractions or treatment sessions over a defined time) for breast irradiation has not been uniformly accepted, we examined whether a 22-day fractionation schedule was as effective as the more traditional 35-day schedule in reducing recurrence. METHODS: Women with invasive breast cancer who were treated by lumpectomy and had pathologically clear resection margins and negative axillary lymph nodes were randomly assigned to receive whole breast irradiation of 42.5 Gy in 16 fractions over 22 days (short arm) or whole breast irradiation of 50 Gy in 25 fractions over 35 days (long arm). The primary outcome was local recurrence of invasive breast cancer in the treated breast. Secondary outcomes included cosmetic outcome, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System. All statistical tests were two-sided. RESULTS: From April 1993 through September 1996, 1234 women were randomly assigned to treatment, 622 to the short arm and 612 to the long arm. Median follow-up was 69 months. Five-year local recurrence-free survival was 97.2% in the short arm and 96.8% in the long arm (absolute difference = 0.4%, 95% confidence interval [CI] = -1.5% to 2.4%). No difference in disease-free or overall survival rates was detected between study arms. The percentage of patients with an excellent or good global cosmetic outcome at 3 years was 76.8% in the short arm and 77.0% in the long arm; the corresponding data at 5 years were 76.8% and 77.4%, respectively (absolute difference = -0.6%, 95% CI = -6.5% to 5.5%). CONCLUSION: The more convenient 22-day fractionation schedule appears to be an acceptable alternative to the 35-day schedule.     

Comparison of mammographic findings after intraoperative radiotherapy or external beam whole breast radiotherapy

Background

The TARGIT (TARGeted Intraoperative Radiotherapy) trial was designed to compare local recurrence and complication rates in breast cancer patients, prospectively randomised to either EBRT (external beam whole breast radiotherapy) or a single dose of IORT (intraoperative radiotherapy). The aim of our study was to compare follow-up mammographic findings, ultrasound and biopsy rates in each group.

Methods

Follow-up imaging and breast biopsies of women from one centre participating in the TARGIT-A trial were independently reviewed by two radiologists blinded to the radiotherapy treatment received.

Results

The cohort consisted of 141 patients (EBRT n = 80/IORT n = 61). There was no significant difference in the patient or disease characteristics of the two groups. The number of follow-up mammograms and length of follow-up was similar (EBRT/IORT n = 2.0/2.4; 4.3yr/5.1yr; p = 0.386 χ² test). There were no significant differences in mammographic scar or calcification appearances of the post-operative site. Generalised increase in breast density and skin thickening were more common in the EBRT compared to the IORT group (p = 0.002; p = 0.030, χ² test respectively). A trend towards additional ultrasound at follow-up was observed in the IORT group (15 of 61 [24.6%] versus 11 of 80 [13.8%]), however this was not statistically significant (p = 0.100 χ² test). No disease recurrence was demonstrated on any of the breast biopsies taken. Only one biopsy was reported as fat necrosis in the IORT group.

Conclusions

Mammographic changes were more common following EBRT, although more additional follow-up ultrasounds were performed in the IORT group. IORT is not detrimental to subsequent radiological follow up.