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This article presents an outcomes review of breast cancer patients identified from the cancer registries of four area hospitals. These patients had family histories of breast cancer, ovarian carcinoma, or both and were treated with conservative surgery and radiation to the involved breast. Patients were as follows: group 1, one first-degree relative ( n = 165, one synchronous bilateral breast cancer); group 2, > or =2 first-degree relatives ( n = 21); group 3, one second-degree relative ( n = 20); and group 4, > or =2 second-degree relatives ( n = 18). The total of patients and breast cancer events was 224 and 225, respectively. Group 5 was a subgroup of 53 patients with a substantial risk (>10%) of a BRCA1 or BRCA2 mutation. After a median follow-up of 3.9 years, 5 patients had local failure (2%), and 5 developed a contralateral breast cancer (2%). There were no significant differences in local failure rates between groups (p = 1.0): group 1, 5 of 166 (3%); group 2, 0 of 21 (0%); group 3, 0 of 20 (0%); and group 4, 0 of 18 (0%). Local failure for group 5 was 2% (1 of 53). Four of 143 patients (3%) with a minimum 3 years of follow-up (median, 5.6 years) had local failure, and 5 (4%) developed a contralateral breast cancer. A univariate analysis was statistically significant for differentiation only (well, 0 of 67; moderately, 1 of 57 [1.8%]; poor, 3 of 26 [11.5%], p = 0.008). Overall survival for groups 1-4 did not differ significantly. Although follow-up has been relatively short, we have not found that breast cancer patients with various degrees of family histories of breast/ovarian carcinoma have had a detrimental outcome when treated with conservative therapy.
OBJECTIVE: To help physicians and their patients arrive at optimal strategies for breast radiotherapy after breast-conserving surgery (BCS) for early breast cancer. OUTCOMES: Local control, survival, quality of life, adverse effects of irradiation and cosmetic results. EVIDENCE: A literature search using MEDLINE from 1966 and CANCERLIT from 1983, to Jan. 1, 1997. The evidence is graded in 5 levels (page S2). BENEFITS: A decrease in local recurrence of breast cancer. HARMS: Adverse effects of breast irradiation. RECOMMENDATIONS: Women who undergo BCS should be advised to have postoperative breast irradiation. Omission of radiotherapy after BCS almost always increases the risk of local recurrence. Contraindications to breast irradiation include pregnancy, previous breast irradiation (including mantle radiation for Hodgkin's disease) and inability to lie flat or to abduct the arm. Scleroderma and systemic lupus erythematosus constitute relative contraindications. The commonest fractionation schedule used in Canada is 50 Gy in 25 fractions to the whole breast without a boost when excision margins are clear of disease. Alternative schedules that may be used range from 40 Gy in 16 fractions to the whole breast, with or without a boost, to 45 Gy in 25 fractions with a boost of 16 Gy in 8 fractions to the primary site. The role of boost irradiation to the primary site is unclear. Irradiation of the whole breast rather than partial irradiation is recommended. When choices are being made between different treatment options, patients must be made aware of the acute and late complications that can result from radiotherapy. Physicians should adhere to standard treatment regimens to minimize the adverse effects of irradiation. It is recommended that local breast irradiation should be started as soon as possible after surgery and not later than 12 weeks after, except for patients in whom radiotherapy is preceded by chemotherapy. However, the optimal interval between BCS and the start of irradiation has not been defined. The optimal sequencing of chemotherapy and irradiation is not clearly defined for patients who are also candidates for chemotherapy. Most centers favour the administration of chemotherapy before radiotherapy. Selected chemotherapy regimens are sometimes used concurrently with radiotherapy. There is no evidence that this results in better outcome, and there is an increased chance of toxic effects, especially for anthracycline-containing regimens. VALIDATION: Earlier drafts of these guidelines were reviewed, discussed and approved by the Breast Disease Site Group of the Ontario Cancer Treatment and Research Foundation. They were next revised by a writing committee and by expert primary reviewers and secondary reviewers selected from all regions of Canada. The final version was approved by the Steering Committee and reflects a consensus of all these contributors. It has been endorsed by the Canadian Association of Radiologists.
As an integral part of a quality assurance programme, this survey was undertaken to establish precise details of breast radiation techniques used within centres expressing an interest to participate in the START Trial--a U.K. multi-centre randomised trial of different dose fractionation schedules for breast cancer. A questionnaire was circulated between November 1997 and January 1999 to 56 U.K. radiotherapy centres. This covered specific details of patient immobilisation, technique and dose fractionation when treating breast or chest wall, supraclavicular fossa and axilla and when directing a boost to the tumour bed. Variations in technique, incorporating immobilisation, treatment energy and dose prescription span the entire radiation treatment process from localisation to planning and subsequent treatment. A range of dose/fraction/time schedules were used for tangential fields, nodal fields and the tumour bed boost. As part of the quality assurance programme for the START Trial this independent review of breast radiotherapy practice has provided a baseline of techniques used by centres prior to participating in the trial. It has also presented a view of the complexity of the issues to enable the design of the next phase of the quality assurance programme. Adherence to the trial protocol will ensure acceptable technique and dosimetry across centres.
BACKGROUND: Radiation dose distributions created by two dimensional (2D) treatment planning are responsible for partial volumes receiving >107% of the prescribed dose in a proportion of patients prescribed whole breast radiotherapy after tumour excision of early breast cancer. These may contribute to clinically significant late radiation adverse effects. AIM: To test three dimensional (3D) intensity modulated radiotherapy (IMRT) against 2D dosimetry using standard wedge compensators in terms of late adverse effects after whole breast radiotherapy. METHODS: Three hundred and six women prescribed whole breast radiotherapy after tumour excision for early stage cancer were randomised to 3D IMRT (test arm) or 2D radiotherapy delivered using standard wedge compensators (control arm). All patients were treated with 6 or 10MV photons to a dose of 50Gy in 25 fractions to 100% in 5 weeks followed by an electron boost to the tumour bed of 11.1Gy in 5 fractions to 100%. The primary endpoint was change in breast appearance scored from serial photographs taken before radiotherapy and at 1, 2 and 5 years follow up. Secondary endpoints included patient self-assessments of breast discomfort, breast hardness, quality of life and physician assessments of breast induration. Analysis was by intention to treat. RESULTS: 240 (79%) patients with 5-year photographs were available for analysis. Change in breast appearance was identified in 71/122 (58%) allocated standard 2D treatment compared to only 47/118 (40%) patients allocated 3D IMRT. The control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for year of photographic assessment (95% confidence interval 1.2-2.5, p=0.008). Significantly fewer patients in the 3D IMRT group developed palpable induration assessed clinically in the centre of the breast, pectoral fold, infra-mammary fold and at the boost site. No significant differences between treatment groups were found in patient reported breast discomfort, breast hardness or quality of life. CONCLUSION: This analysis suggests that minimisation of unwanted radiation dose inhomogeneity in the breast reduces late adverse effects. Incidence of change in breast appearance was statistically significantly higher in patients in the standard 2D treatment arm compared with the IMRT arm. A beneficial effect on quality of life remains to be demonstrated.
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PURPOSE: In breast radiotherapy, delivery of manually-calculated electron boosts limits retrospective dose-response analyses as dose distribution is unavailable. This work evaluates the feasibility of reconstructing dose distributions from manually planned electron boosts in breast-conserving radiotherapy. METHODS: Only 72 out of 198 breast cancer patients had complete stored dose distributions from sequential electron boosts in the REQUITE study. Arbitrary data from 70/72 patients were used to develop and validate dose reconstruction method. Twenty patients were used to determine optimal parameters for Monte-Carlo-based (MC) electron dose reconstruction on RayStation (v.11B-R), considering CT-calibration curve, MC-history number, andcalculation grid resolution. Remaining 50 patients were used to quantify dose reconstruction accuracy. The similarity between reconstructed and stored dose was evaluated using 3D-gamma index and dosimetric parameters extracted from breast and tumour bed contours. Dose difference location was evaluated using dose-location histogram. RESULTS: Calculation grid resolution significantly impacted electron dose distribution (p < 0.01), where the finest grid (0.15 cm) showed highest similarity to stored doses. CT-calibration curve and MC-history number had a negligible influence on dose reconstruction. Dosimetric difference between reconstructed and stored doses was < 1 Gy for breast and tumour bed. Reconstructed dose was achieved > 90% gamma passing rate in the validation set. However, around 2.5 Gy dose differences were observed at the skin and tissue interface regions. CONCLUSIONS: Retrospective electron boost dose reconstruction is feasible with acceptable accuracy, and could increase data completeness in large cohort studies. Caution is advised when assessing dose near tissue interface and further validation is needed outside the REQUITE dataset.
Lumpectomy and whole-breast radiotherapy (ie, breast-conservation treatment) are accepted as viable alternatives to mastectomy in locoregional management of breast cancer. These techniques are used to keep morbidity to a minimum, optimise cosmesis, and maintain treatment outcomes. Pathological and clinical data suggest that most recurrences of cancer in the ipsilateral breast are in the vicinity of the index lesion, and that remote recurrences are uncommon, whether or not whole-breast radiotherapy is delivered. These data lend support to the idea of partial-breast radiotherapy. Such a restricted treatment volume allows safe delivery of an accelerated hypofractionated regimen over a shortened course of 1 week. This technique differs from that of standard whole-breast tangential external-beam radiotherapy and necessitates investigation of accelerated partial-breast irradiation (APBI). Several techniques of APBI are being investigated; however, most experience, and the most favourable early outcomes, has been obtained with image-guided breast brachytherapy. This review highlights the rationale and outcomes of brachytherapy techniques.
PURPOSE: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0-II breast cancer. MATERIALS AND METHODS: Fifty-six patients with clinical Stage 0-II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D-44EE). Cosmesis was evaluated on a 1-10 (worst-to-best) scale. RESULTS: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8-10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. CONCLUSION: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.
BACKGROUND: Breast radiotherapy has a low incidence of long term complications. Lymphedema is the most commonly reported complication and adversely affects the quality of life of the breast carcinoma patient. Although its incidence is decreasing, lymphedema still remains a significant concern for patients and their physicians. With the indications for radiotherapy in breast carcinoma management broadening, current strategies to prevent radiation-related lymphedema should be applied and new strategies should be developed. METHODS: A review of the literature addressing lymphedema as a complication of radiotherapy in breast carcinoma management was performed. RESULTS: Arm, breast, and truncal edema occur after primary breast carcinoma management. The literature supports the view that radiotherapy contributes to arm and breast edema. Lymphedema occurs most commonly in patients who have both axillary radiotherapy and surgery, is often triggered by a soft tissue infection, and is more common in obese patients. The incidence of arm edema is decreasing due to more conservative surgical treatment of the axilla and possibly due to more conservative management of the breast. Trends in breast edema are less discernible. Single-modality treatment of the axilla is associated with a very low incidence of arm edema. CONCLUSIONS: Lymphedema continues to be a problem in the care of the breast carcinoma patient. More conservative surgery combined with careful patient selection for nodal radiotherapy reduces its incidence. Radiotherapy technique, prompt treatment of soft tissue infections, and weight loss in obese patients each can contribute to prevention. The risk of lymphedema is greatly surpassed by the benefits of radiotherapy in the care of the breast carcinoma patient.
PURPOSE: To examine the ability of computer planning systems to calculate the dose to the breast correctly in three dimensions. Both the absolute dose at the center of the breast and the accuracy of the isodose distributions were investigated. METHODS AND MATERIALS: Measurements were performed in a water-filled breast phantom using an ionization chamber. Thirty-six sets of data obtained during the Standardization of Breast Radiotherapy breast fractionation trial quality assurance program were included in the analysis. The planning systems were grouped according to the algorithms used on the basis of the definitions given in International Commission on Radiation Units and Measurements Report No. 24. RESULTS: Thirty-two of the 36 planning systems overestimated the dose to the center of the breast, with a mean measured/calculated dose ratio of 0.979 (SD 0.013). The relative dose within 2 cm of the lung was also overestimated. CONCLUSION: Only one algorithm (collapsed cone) investigated in this study was able to calculate the dose at the center of the breast correctly in tangential breast radiotherapy. With modern algorithms, it is important to include a correction for the lower density of the lung, because the dose close to the interface between breast and lung tissue will also be lower than anticipated.
Breast radiotherapy is still in progress. The target volumes - whole breast and lymph nodes - are usually located by clinical palpation and the use of bony landmarks. However computed tomography has allowed a better definition of the deep edge of the volumes and the calculation of 3D dose distributions. A survey of 194 centers has started in June 2005 in France. The questionnaire that was sent included questions about general techniques in breast radiotherapy. Preliminary results on 50 centers showed that patient anatomical data were in the vast majority acquired by a simulator-CT or a CT (for 92%). In the 50 departments, beam placement is done either directly at the simulator (20 centers), or on the TPS (16 centers). Virtual simulation software is used in 8 centers. In about 20% (11) radiotherapy departments, 3D target volumes are contoured and the beams adapted to their shapes.
BACKGROUND AND PURPOSE: Adjuvant breast radiotherapy (RT) is now part of the routine care of patients with early breast cancer. However, analysis of the Early Breast Cancer Trialists' Collaborative suggests that patients with the lowest risk of dying of breast cancer are at significant risk of cardiac mortality due to longer relapse-free survival. Patients with a significant amount of heart in the high-dose volume have been shown to be at risk of fatal cardiac events. This study was designed to assess whether conformal planning or intensity-modulated radiotherapy (IMRT) techniques allow reduced cardiac irradiation whilst maintaining full target coverage. MATERIAL AND METHODS: Ten patients with early breast cancer were available for computed tomography (CT) planning. Each had at least 1 cm maximum heart depth within the posterior border of conventional tangents. For each patient, plans were generated and compared using dose volume histograms for planning target volume (PTV) and organs at risk. The plans included conventional tangents with and without shielding. The shielding was designed to either completely spare the heart or to shield as much heart as possible without compromising PTV coverage. IMRT plans were also prepared using two- and four-field tangential and six-field arc-like beam arrangements. RESULTS: PTV homogeneity was better for the tangential IMRT techniques. For all patients, cardiac irradiation was reduced by the addition of partial cardiac shielding to conventional tangents, without compromise of PTV coverage. The two- and four-field IMRT techniques also reduced heart doses. The average percentage volume of heart receiving >60% of the prescription dose was 4.4% (range 1.0-7.1%) for conventional tangents, 1.5% (0.2-3.9%) for partial shielding, 2.3% (0.5-4.6%) for the two-field IMRT technique and 2.2% (0.4-5.6%) for the four-field IMRT technique. For patients with larger maximum heart depths the four-field IMRT plan achieved greater heart sparing than the partial shielding, although irradiation of the contralateral breast was increased. Full cardiac shielding resulted in the most complete heart sparing but with compromise of the PTV coverage; the mean volume receiving less than 95% of the prescription dose was 4% (range 1.5-8.7%). CONCLUSION: All patients undergoing adjuvant tangential breast RT in whom the heart is seen to be in the high-dose volume should be considered for the addition of cardiac-sparing lead blocks. Three-dimensional CT planning and alternative beam arrangements with IMRT optimization enables more complete cardiac sparing without compromise of PTV coverage in certain patients.
BACKGROUND: The objective of this study was to determine if standard tangential breast radiation covered the sentinel lymph node in women with invasive breast cancer. METHODS: Women with invasive breast cancer treated by lumpectomy, radiotherapy and sentinel node biopsy at our institution were included in this study if the sentinel lymph node site had been marked with a clip. Plain films were used to determine if the clip fell within the tangential fields. RESULTS: Between April 1999 and May 2001, 36 women with invasive breast cancer treated by lumpectomy, sentinel lymph node biopsy and breast radiation were identified. Median age was 56 years (range 34 to 80) with a median tumor size of 1.1 cm (range 0.3 to 2.9 cm). The clip marking the sentinel lymph node fell within the tangential fields in 34 of 36 (94%) of the patients. The radiation dose to the clip area was greater than 4,400 cGy in 50% of those calculated by three-dimensional techniques. CONCLUSIONS: The sentinel lymph node is located within classic tangential fields in the overwhelming majority of women with invasive breast cancer. The extent of the radiation fields, and ultimately the final dose, may need to be modified if the intent is for prophylactic treatment.
PURPOSE: Prone-position breast radiotherapy (RT) has been described as an alternative technique to improve dose homogeneity for women with large, pendulous breasts. We report the feasibility and dosimetric analysis of a simplified intensity-modulated RT (IMRT) technique, previously reported for women in the supine treatment position, to plan prone-position RT to the intact breast. METHODS AND MATERIALS: Twenty patients with clinical Stage TisN0-T1bN1 breast cancer undergoing breast-conserving therapy underwent whole breast RT using a prone position technique. The treatment plans were developed using both conventional tangents and a simplified intensity-modulated tangential beam technique based on optimization of the intensity distributions across the breast. The plans were compared with regard to the dose-volume parameters. RESULTS: Dose heterogeneity within the breast planning target volume was significantly greater for the conventional tangent plans. Of 20 patients, 16 (80%) received maximal doses of > or =110% using the conventional tangents vs. only 1 (5%) using the IMRT plan. The isodose level encompassing 5% of the planning target volume was reduced from an average of 110% with conventional tangents to 105% with IMRT. The maximal dose within the planning target volume was reduced from an average of 114% with conventional tangents to 107% with IMRT. The greatest improvement was seen in the patients with the most pendulous breasts. CONCLUSION: An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, pendulous breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact acute toxicity and cosmetic outcome in this cohort of women who have historically suffered from poor cosmesis after breast-conserving therapy.
INTRODUCTION: Fatigue is commonly reported in patients receiving radiotherapy for breast conservation, but the underlying mechanisms remain unclear. METHODS: Patients with early breast cancer participating in a prospective study of the impact of inflammatory processes on early and delayed breast morbidity were assessed for fatigue levels using the Functional Assessment of Cancer Therapy (FACT) fatigue subscale before and at intervals during and after radiotherapy. Blood for analysis of a variety of circulating cytokines, coagulation factors, peripheral blood indices and biochemical factors was collected at the same time points. RESULTS: Fifty-two eligible patients were assessed. Twenty-one patients (43%) developed significant fatigue during radiotherapy, whereas 28 (54%) developed minimal or no fatigue. Fatigue appeared to plateau between week 4 of treatment and 2 weeks after treatment. The fatigue was beginning to settle by 6 weeks after treatment. Significant fatigue was predicted by a higher baseline fatigue score, red cell count, neutrophil count, and D-dimer level. Baseline fatigue correlated with higher body mass index, C-reactive protein, soluble thrombomodulin, tissue plasminogen activator, von Willebrand factor antigen, interleukin-6, ICAM-1, hemoglobin and red cell, monocyte, and neutrophil counts. There were also significant correlations between body mass index and tissue plasminogen activator, C-reactive protein, interleukin-6, ICAM-1, and red cell count. After these factors were controlled for, baseline fatigue was seen to be associated with higher body mass index, soluble thrombomodulin, tissue plasminogen activator, von Willebrand factor antigen, monocyte count, and neutrophil count. Multiple logistic regression procedures indicated that the most predictive factors for fatigue during radiotherapy were higher baseline fatigue level and higher baseline neutrophil and red cell counts. CONCLUSION: This study has shown that significant fatigue is common in patients receiving breast irradiation and is precipitated during radiotherapy in some patients but not others. The factors shown to be associated with fatigue in this study will be helpful in shaping future studies.
PURPOSE: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom. EXPERIMENTAL DESIGN: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points. RESULTS: No increase in clinically significant late toxicity was seen in the mutation carriers. CONCLUSIONS: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.
PURPOSE: To report the 7-year results of a prospective study of accelerated partial breast irradiation (APBI) using interstitial high-dose-rate brachytherapy and compare the treatment results with those achieved by standard, whole breast radiotherapy (WBRT), with or without a tumor bed boost (TBB). METHODS AND MATERIALS: Between 1996 and 1998, 45 prospectively selected patients with T1N0-N1mi (single nodal micrometastasis), nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI using interstitial high-dose-rate implants. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumor bed plus a 1-2-cm margin. During the same period, 80 patients, who met the eligibility criteria for APBI but who were treated with 50 Gy WBRT with (n = 36) or without (n = 44) a 10-16-Gy TBB, were selected as controls. The median follow-up for the APBI and control groups was 81 and 83 months, respectively. Local control, relapse-free survival, cancer-specific survival, late side effects, and cosmetic results were assessed. RESULTS: The crude rate of total ipsilateral breast failure was 6.7% (3 of 45), 11.4% (5 of 44), and 8.3% (3 of 36) for patients treated with APBI, WBRT, and WBRT + TBB, respectively. The differences in the 5- and 7-year actuarial rates of ipsilateral breast recurrence were not statistically significant among patients treated with APBI (4.4% and 9.0%), WBRT (4.7% and 14.8%), and WBRT + TBB (5.7% and 9.5%). No statistically significant difference in either the 7-year probability of relapse-free survival (79.8%, 73.5%, and 77.7% for APBI, WBRT, and WBRT + TBB, respectively) or cancer-specific survival (93.3%, 92.9%, and 93.9% for APBI, WBRT, and WBRT + TBB, respectively) was found. The 7-year actuarial elsewhere breast failure rate was 9.0% in the APBI group and 8.3% in the control group (p = 0.80). The rate of excellent/good cosmetic results was 84.4% in the APBI group and 68.3% in the control group (p = 0.04). The corresponding rates of asymptomatic fat necrosis were 20.0% and 20.6%. Symptomatic fat necrosis occurred in 1 patient (2.2%) treated with APBI. The incidence of Grade 2 or worse late radiation side effects was similar for both groups (26.7% vs. 28.6%). CONCLUSION: Accelerated partial breast irradiation using interstitial high-dose-rate implants, with proper patient selection and quality assurance, yields similar 7-year results to those achieved with standard breast-conserving therapy. APBI does not increase the risk of elsewhere breast failures.