The guideline for postmastectomy radiotherapy (PMRT), which is prescribed to reduce recurrence of breast cancer in the chest wall and improve overall survival, is not always followed. Identifying and extracting important patterns of non-compliance are crucial in maintaining the quality of care in Oncology.
Analysis of 759 patients with malignant breast cancer using decision tree induction (DTI) found patterns of non-compliance with the guideline. The PMRT guideline was used to separate cases according to the recommendation to receive or not receive PMRT. The two groups of patients were analyzed separately. Resulting patterns were transformed into rules that were then compared with the reasons that were extracted by manual inspection of records for the non-compliant cases.
Analyzing patients in the group who should receive PMRT according to the guideline did not result in a robust decision tree. However, classification of the other group, patients who should not receive PMRT treatment according to the guideline, resulted in a tree with nine leaves and three of them were representing non-compliance with the guideline. In a comparison between rules resulting from these three non-compliant patterns and manual inspection of patient records, the following was found:
In the decision tree, presence of perigland growth is the most important variable followed by number of malignantly invaded lymph nodes and level of Progesterone receptor. DNA index, age, size of the tumor and level of Estrogen receptor are also involved but with less importance. From manual inspection of the cases, the most frequent pattern for non-compliance is age above the threshold followed by near cut-off values for risk factors and unknown reasons.
Comparison of patterns of non-compliance acquired from data mining and manual inspection of patient records demonstrates that not all of the non-compliances are repetitive or important. There are some overlaps between important variables acquired from manual inspection of patient records and data mining but they are not identical. Data mining can highlight non-compliance patterns valuable for guideline authors and for medical audit. Improving guidelines by using feedback from data mining can improve the quality of care in oncology.
We aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM).
Ninety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed.
Differences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3%vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90,2% vs 61,9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS.
PMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.
The role of post-mastectomy radiotherapy (PMRT) in patients with T1-2 and 1-3 positive lymph nodes remains controversial. The aim of this study is to investigate the possible benefits of PMRT for this subgroup.
Three electronic databases were systematically quarried (Cochrane Library, MEDLINE, and EMBASE) for published studies evaluating the effects of PMRT on breast cancer patients with T1-T2 tumors with 1-3 positive lymph nodes. Of the 334 studies identified, information was available for 3432 patients from 10 clinical studies. Pooled relative risk estimates (RR) and overall survival (OS) were calculated using the inverse variance weighted approach, publication bias and chi-square test were also calculated.
From the 10 studies, the pooled RR (RRs) for locoregional recurrence (LRR) with PMRT was 0.348 (95% CI = 0.254 to 0.477), suggesting a significant benefit for PMRT to decrease the risk of LRR in patients with T1-T2 tumors and 1-3 positive nodes (p<0.05). Reporting bias ( Begg’s p = 0.152; Egger’s p = 0.107) or significant heterogeneity (Cochran’s p = 0.380; I2 = 6.7%) were not detected. For further subset analysis, the RR for T1, N1-3+ tumors was 0.330 (95% CI = 0.171 to 0.639); for T2, N1-3+ tumors the RR was 0.226 (95% CI = 0.121 to 0.424). The pooled RR for overall survival (OS) was not significantly different between PMRT and no-PMRT group (1.051, 95% CI =1.001 to 1.104).
Our pooled analysis revealed that PMRT significantly reduces the risk of LRR in patients with TI-T2 tumors with 1-3 positive nodes, and the magnitude of the LRR risk reduction is slightly greater for larger tumors. Our results suggest that PMRT should be considered for patients with T1/T2 tumors with 1-3 positive nodes to decrease the relatively high risk of LRR.
Given accumulating evidence supporting postmastectomy radiotherapy (PMRT) in selected patients, it is important to evaluate patterns and correlates of PMRT utilization, including communication and attitudinal factors.
The authors surveyed 2382 patients diagnosed with breast cancer in 2002 and reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries (n = 1844, 77.4% response rate). Analyses were restricted to patients with nonmetastatic invasive breast cancer treated by mastectomy who had decided whether or not to undergo PMRT (n = 396). The authors assessed rates of explanation, recommendation, and receipt of radiation by indication grouping, defined primarily by the 2001 American Society of Clinical Oncology guidelines. They evaluated correlates of PMRT receipt, including tumor and sociodemographic characteristics. They also explored patients’ self-reported reasons for nonreceipt of PMRT.
The adjusted proportion in each indication group reporting that a provider had explained radiation was high (77% of those in whom PMRT was indicated, 76% of those in whom medical opinion was divided, and 73% of those in whom PMRT was not indicated; P = .10). The adjusted proportions reporting recommendations for radiation (86%, 35%, and 17%, respectively) and receipt (81%, 34%, and 10%, respectively) varied significantly by indication grouping (P < .001). On multivariate analysis, tumor size (P < .001), lymph node status (P < .001), comorbidity (P = .02), and chemotherapy receipt (P = .003) were found to be independent significant correlates of PMRT receipt. The most common reasons cited for not pursuing PMRT were lack of physician recommendation and perceived lack of need.
PMRT receipt is strongly correlated with clinical indication. The authors found no sociodemographic disparities in utilization. However, approximately one-fifth of patients with strong indications did not receive treatment.
mastectomy; radiotherapy; breast neoplasms; guideline adherence; quality of healthcare
This study compared the clinical outcomes of T1-2N1 breast cancer patients with and without postmastectomy radiotherapy (PMRT). Risk factors for loco-regional recurrence (LRR) were identified in order to define a subgroup of patients who might benefit from PMRT.
Materials and Methods
Of 110 T1-2N1 breast cancer patients who underwent mastectomy from January 1994 through December 2009, 32 patients underwent PMRT and 78 patients did not. Treatment outcomes and risk factors for LRR were analyzed.
The 5- and 10-year LRR rates were both 6.2% in the PMRT group, and 10.4% and 14.6% in the no-PMRT group (p=0.336). In addition, no significant differences in distant metastasis-free survival (DMFS) or overall survival (OS) were observed between patients receiving and not receiving PMRT. In multivariate analysis, factors associated with higher LRR rates included grade 3 disease, extracapsular extension (ECE), and triple negative subtype. Patients who had one or more risk factors for LRR were defined as a high-risk patient group. In the high-risk group, both 5- and 10-year LRR rates for patients who underwent PMRT was 18.2%, and LRR rates of 21.4% at five years and 36.6% at 10 years were observed for patients who did not undergo PMRT (p=0.069).
PMRT in T1-2N1 breast cancer patients should be considered according to several prognostic factors in addition to T and N stage. Findings of our study indicated that PMRT did not improve LRR, DMFS, or OS in T1-2N1 breast cancer patients. However, in a subgroup of patients with grade 3 disease, ECE, or triple negative subtype, PMRT might be beneficial.
Breast neoplasms; Radiotherapy; Mastectomy; Risk factor
Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1–3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand. Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001–2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients). Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model. Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1–3 node positive early-stage breast cancer.
postmastectomy radiotherapy; 1–3 positive nodes; breast cancer; Thai
The impact of postmastectomy radiotherapy (PMRT) on locoregional recurrence–free survival (LRFS) and disease-free survival (DFS) outcomes was investigated in patients with triple-negative breast cancer. PMRT was associated with longer LRFS and DFS times in high-risk TNBC patients and a longer DFS time in intermediate-risk TNBC patients.
Evaluate the effect of postmastectomy radiotherapy (PMRT) in terms of locoregional recurrence-free survival and disease-free survival in triple-negative breast cancer (TNBC) patients.Identify the subgroup of TNBC patients most likely to benefit from PMRT.Assess the role of PMRT in TNBC patients with intermediate-risk (T1/2N1) disease.
Several studies have demonstrated poor locoregional control in patients with triple-negative breast cancer (TNBC), compared with other molecular subtypes of breast cancer. We sought to evaluate whether or not postmastectomy radiotherapy (PMRT) improves locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) outcomes in TNBC patients.
Methods and Materials.
Between January 2000 and July 2007, 553 TNBC patients treated with modified radical mastectomy from a single institution were analyzed retrospectively. Patients were categorized into three groups: low risk (stage T1–T2N0), intermediate risk (stage T1–T2N1), and high risk (stage T3–T4 and/or N2–N3). Cox proportional hazards models were used to evaluate the association between PMRT and LRFS and DFS times after adjusting for other clinicopathologic covariates.
With a median follow-up of 65 months (range, 1–140 months), 51 patients (9.2%) developed locoregional recurrence and 135 patients (24.4%) experienced disease recurrence. On multivariate analysis, PMRT was associated with significantly longer LRFS and DFS times in the entire cohort. In the intermediate-risk group, PMRT was associated with a longer DFS time but not with the LRFS interval. In the high-risk group, PMRT was associated with significantly longer LRFS and DFS times.
PMRT is associated with longer LRFS and DFS times in high-risk TNBC patients and a longer DFS time in intermediate-risk TNBC patients. Prospective randomized studies are needed to investigate the best locoregional treatment approaches for patients with this molecular subtype of breast cancer.
Breast cancer; Triple negative; Postmastectomy radiotherapy; Locoregional recurrence; Disease-free survival
Postmastectomy radiation therapy (PMRT) can reduce locoregional recurrences (LRR) in high-risk patients, but its role in the treatment of lymph node negative (LN−) breast cancer remains unclear. The aim of this study was to identify a subgroup of T1-T2 breast cancer patients with LN− who might benefit from PMRT.
Methods and Materials
We retrospectively reviewed 1,136 node-negative T1-T2 breast cancer cases treated with mastectomy without PMRT at the Massachusetts General Hospital between 1980 and 2004. We estimated cumulative incidence rates for LRR overall and in specific subgroups, and used Cox proportional hazards models to identify potential risk factors.
Median follow-up was 9 years. The 10-year cumulative incidence of LRR was 5.2% (95% CI: 3.9–6.7%). Chest wall was the most common (73%) site of LRR. Tumor size, margin, patient age, systemic therapy, and lymphovascular invasion (LVI) were significantly associated with LRR on multivariate analysis. These five variables were subsequently used as risk factors for stratified analysis. The 10-year cumulative incidence of LRR for patients with no risk factors was 2.0% (95% CI: 0.5–5.2%), whereas the incidence for patients with three or more risk factors was 19.7% (95% CI: 12.2–28.6%).
It has been suggested that patients with T1-T2N0 breast cancer who undergo mastectomy represent a favorable group for which PMRT renders little benefit. However, this study suggests that select patients with multiple risk factors including LVI, tumor size ≥2 cm, close or positive margin, age ≤50, and no systemic therapy are at higher risk of LRR and may benefit from PMRT.
Breast cancer; Mastectomy; Postmastectomy radiation; Risk factors; Locoregional recurrence
The aim of this study was to quantify the variation in doses to organs at risk (ipsilateral lung and heart) and the clinical target volume (CTV) in the presence of breast implants. In this retrospective cohort study, patients were identified through the National Breast Cancer Register. Consecutive breast cancer patients undergoing mastectomy between 2009 and 2011 and completing a full course of postmastectomy radiotherapy (PMRT) were eligible. All included patients (n = 818) were identified in the ARIA© oncology information system and further stratified for immediate breast reconstruction (IBR+, n = 162) and no immediate breast reconstruction (IBR-, n = 656). Dose statistics for ipsilateral lung, heart and CTV were retrieved from the system. Radiation plans for patients with chest wall (CW) only (n = 242) and CW plus lymph nodes (n = 576) irradiation were studied separately.
The outcome variables were dichotomized as follows: lung, V20Gy ≤ 30% vs. V20Gy > 30%; heart, Dmean ≤ 5 Gy vs. Dmean > 5 Gy; CTV, V95% ≥ median vs. V95% < median.
In the univariate and multivariate regression models no correlation between potential confounders (i.e. breast reconstruction, side of PMRT, CW index) and the outcome variables was found. Multivariate analysis of CW plus lymph nodes radiation plans, for example, showed no association of breast reconstruction with dosimetric outcomes in neither lung nor heart- lung V20Gy (odds ratio [OR]: 0.6, 95%CI, 0.4 to 1.0, p = 0.07) or heart Dmean (OR: 1.2, 95%CI, 0.5 to 3.1, p = 0.72), respectively.
CTV was statistically significantly larger in the IBR+ group (i.e. included breast implant), but no correlation between the implant type and dosimetric characteristics of the organs at risk was revealed.
In the current study, the presence of breast implants during postmastectomy radiotherapy was not associated with increased doses to ipsilateral lung and heart, but CTV definition and its dosimetric characteristics urge further evaluation.
Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT).
Patients and methods
Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years.
Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0–7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0–7 uninvolved nodes (5.2%). In patients with 1–3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0–7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site.
PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1–3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0–7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
adjuvant treatment; breast cancer; locoregional recurrence; postmastectomy radiotherapy
Immediate breast reconstruction after mastectomy and delayed breast reconstruction with post-supplementary treatment are the two types of breast reconstruction currently performed when treating breast cancer. Post-mastectomy radiation therapy (PMRT) not only reduces local recurrence but also improves overall survival. However, the complications and survival rates associated with PMRT need to be clear when determining the timing of breast reconstruction. Accordingly, we investigated the optimal timing of breast reconstruction by observing patients who underwent mastectomy followed by PMRT, based on their overall health and aesthetic satisfaction.
We retrospectively reviewed 21 patients who underwent breast reconstruction with PMRT between November 2004 and November 2010. We collected data regarding the various methods of mastectomy, and the modality of adjuvant therapy, such as chemotherapy, hormone therapy, and radiotherapy. Telephone interviews were conducted to study the general and aesthetic satisfaction.
Patients who received PMRT after breast reconstruction showed a greater complication rate than those undergoing breast reconstruction after PMRT (P=0.02). Aesthetic satisfaction was significantly higher in the groups undergoing breast reconstruction after PMRT (P=0.03). Patients who underwent breast reconstruction before PMRT developed complications more frequently, but they expressed greater aesthetic satisfaction with the treatment.
It is recommended that the complication rates and aesthetic satisfaction after breast reconstruction be carefully considered when determining the optimal timing for radiotherapy.
Breast; Mastectomy; Radiotherapy
At the first Austrian multidisciplinary expert panel on controversies in local treatment of breast cancer, 22 experts of all relevant disciplines discussed current areas of debate (surgery of the breast, surgery and pathology of the axilla, reconstructive surgery, radiotherapy, and imaging) in local therapy. The most controversial area of debate was the area of axillary surgery. The panel agreed that it was no longer necessary to perform completion axillary lymph node dissection (ALND) when micrometastases are diagnosed in the sentinel lymph node. The only prospective trial comparing patients with sentinel node macrometastases with or without completion ALND had to be terminated early due to failure in sufficient patient recruitment. As long as the frequently discussed issues have not been solved and in light of the lack of any clear level 1 evidence, the panel decided not to recommend omitting axillary dissection in patients with 1 or 2 macrometastases meeting the inclusion criteria of the ACOSOG Z0011 trial. The Austrian panel similarly decided not to recommend omitting axillary dissection in patients with macrometastases and low-risk breast cancer in general. These decisions reflect the increasing skepticism of the scientific community against rapidly shifting paradigms without sufficient and clear evidence.
Breast cancer: local therapy, surgery, radiotherapy; Expert panel
We examined rates and determinants of appropriate and inappropriate use of post-mastectomy radiation (PMRT), as defined by NCCN practice guidelines, among women with Stage I-II breast cancer (AJCC 5th Edition).
Using clinical characteristics, 1,620 consecutive patients at eight NCCN institutions who received mastectomy between 7/97–6/02 were classified into three cohorts according to whether guidelines (1) recommended PMRT, (2) recommended against PMRT, or (3) made no definitive PMRT recommendation. We defined the absence of PMRT in the first cohort as underuse, and receipt of PMRT in the second cohort as overuse. Multivariable logistic regression was applied to investigate the association of clinical and sociodemographic factors with PMRT.
Overall, 23.8% received PMRT. This included 83.6% (199/238) in the “recommend PMRT” cohort, 5.6% (58/1029) in the “recommend against PMRT” cohort, and 38.6% (127/329) in the “consider PMRT” cohort. The only factor associated with underuse in the “recommend PMRT” cohort was not receiving chemotherapy (OR=0.08, p<0.0001). In addition to tumor characteristics, factors associated with overuse in the “recommend against PMRT ” cohort included age<50 (OR=2.28, p=0.048), NCCN institution (OR=1.04–8.29, p=0.026), higher education (OR=1.25–9.01, p=0.001), and no reconstructive surgery (OR=2.44, p=0.019). Factors associated with PMRT in the “consider PMRT” cohort included NCCN institution (OR=3.8–9.01, p<0.0001), age<50 (OR=2.26, p=0.041) and tumor characteristics.
Concordance with definitive treatment guidelines was high. However, when current evidence does not support a definitive recommendation for PMRT, treatment decisions appear to be influenced not only by patient age and clinical characteristics, but also by institution-specific patterns of care.
Breast cancer; guideline adherence; mastectomy; quality of health care
OBJECTIVE: To review recent advances in radiation therapy in treatment of breast cancer. QUALITY OF EVIDENCE: MEDLINE and CANCERLIT were searched using the MeSH words breast cancer, ductal carcinoma in situ, sentinel lymph node biopsy, and postmastectomy radiation. Randomized studies have shown the efficacy of radiation treatment for ductal carcinoma in situ (DCIS) and for invasive breast cancer. MAIN MESSAGE: Lumpectomy followed by radiation is effective treatment for DCIS. In early breast cancer, shorter radiation schedules are as efficacious for local control and short-term cosmetic results as traditional fractionation regimens. Sentinel lymph node biopsy is done in specialized cancer centres; regional radiation is recommended for patients with four or more positive axillary lymph nodes. Postmastectomy radiation has been shown to have survival benefits for high-risk premenopausal patients. Systemic metastases from breast cancer usually respond satisfactorily to radiation. CONCLUSION: Radiation therapy continues to have an important role in treatment of breast cancer. There have been great advances in radiation therapy in the last decade, but they have raised controversy. Further studies are needed to address the controversies.
For patients with early breast cancer and lymph node metastasis, axillary treatment is widely recommended. This is either surgical removal of the axillary lymph nodes, or axillary radiotherapy. The rationale for axillary treatment is that it will reduce the risk of recurrence in the axilla, and may improve survival. However, both treatments are associated with adverse effects, such as lymphedema, pain and sensory loss, and are costly to the health services and to patients. With improvements in adjuvant therapy, routine axillary treatment may no longer offer any overall advantage.
To assess the short and long term benefits and adverse effects of routine axillary treatment (axillary lymph node clearance or axillary radiotherapy) for patients with lymph node positive early-stage breast cancer.
Criteria for potentially eligibility for the study will be that the participants are men and women with early breast cancer and lymph nodes with metastasis. The study compares either axillary treatment with no axillary treatment, or axillary node clearance with axillary radiotherapy, and the study is a randomized trial. Primary outcomes are axillary recurrence, disease-free and overall survival. Secondary outcomes include breast or chest wall recurrence, distant metastasis, time to axillary recurrence, axillary recurrence-free survival, arm morbidity, quality of life and health economic costs. The search strategy will include the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) search portal. Two independent reviewers will assess studies for inclusion in the review, assess study quality and extract data. Characteristics of included studies will be described. Meta-analysis will be conducted using ReVman software.
This review addresses an important clinical question, and results will inform clinical practice and health care policy.
Recent developments in the management of breast cancer have increased the complexity of planning for immediate breast reconstruction. Two recent trials have demonstrated superior locoregional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of postmastectomy radiation therapy (XRT) to mastectomy and chemotherapy. On the basis of these results, the use of postmastectomy XRT in patients with early-stage breast cancer is increasing. Unfortunately, it is difficult to predict the presence or extent of axillary lymph node involvement—a major determinant of the need for postmastectomy XRT—before mastectomy. There are two potential problems with performing an immediate breast reconstruction in a patient who will require postmastectomy XRT. First, postmastectomy XRT can adversely affect the aesthetic outcome of an immediate breast reconstruction. Second, an immediate breast reconstruction can interfere with the delivery of postmastectomy XRT. Chemotherapy before or after reconstruction does not significantly increase the occurrence of wound-healing problems and breast reconstruction does not appear to delay the initiation or resumption of chemotherapy. The increasing use of postmastectomy XRT and chemotherapy in patients with early-stage breast cancer necessitates increased communication between the medical oncologist, radiation oncologist, breast surgeon, and plastic surgeon during treatment planning for these patients.
Breast reconstruction; radiation therapy; neoadjuvant chemotherapy; adjuvant chemotherapy; sentinel node biopsy
This pilot study aimed to evaluate prognostic factors of postmastectomy radiotherapy (PMRT) for breast cancer patients undergoing systemic therapy in either preoperative or postoperative setting.
Between 2003 and 2009, 113 patients received PMRT: 61 underwent preoperative systemic therapy (PST subgroup) and 52 received postoperative systemic therapy (non-PST subgroup).
The median follow-up time was 72.3 months (range, 34.0-109.4 months) for surviving patients. In univariate analysis of all patients, disease-free survival (DFS) was associated with age, nodal ratio (NR), and Ki-67 expression; overall survival (OS) was associated with NR and Ki-67 expression. Pathologic N stage and HER2 expression were marginally associated with DFS and OS. In the non-PST subgroup, DFS was associated with age, NR, venous invasion, and Ki-67 expression; OS was associated with age. In the PST subgroup, DFS was associated with ypN stage and NR; OS was associated with ypN, histologic grade, HER2 expression, and p53 expression. In multivariate analysis of all patients, DFS and OS were significantly associated with NR (p=0.003 and p=0.019, respectively) and Ki-67 expression (p=0.002 and p=0.015, respectively). Patients were classified into low-risk (NR ≤0.2 and Ki-67 ≤20%; n=34), intermediate-risk (NR >0.2 or Ki-67 >20%; n=63), and high-risk (NR >0.2 and Ki-67 >20%; n=16) subgroups. All low-risk patients were alive at the time of analysis. High-risk (p<0.001 and p=0.001, respectively) and intermediate-risk (p=0.022 and p=0.008, respectively) patients had significantly shorter DFS and OS than low-risk patients. This prognostic model was statistically significant for DFS when applied to the PST (p=0.001) and non-PST (p=0.016) subgroups separately.
For breast cancer patients undergoing PMRT, NR and Ki-67 are potential prognostic factors. A model using these factors might help predict a poor prognosis. Whether NR and Ki-67 are also prognostic for different setting of systemic therapy, preoperative or postoperative, warrants further study.
Breast neoplasms; Ki-67 antigen; Lymph nodes; Mastectomy; Radiotherapy
To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT).
Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR).
Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17–0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT.
This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.
breast neoplasms; lymph node ratio; pN1; prognostic factor; predictive factor; post-mastectomy radiation therapy
The Z11 trial demonstrated a subgroup of patients with low axillary burden who do not benefit from axillary lymph node dissection (ALND) at short-term follow-up when treated with adjuvant whole-breast radiotherapy and systemic therapy. We consider the role of sentinel lymph node biopsy (SLNB) and look at and beyond the Z11 trial to consider further imaging studies, which may offer truly minimally invasive management of the axilla and relegate SLNB to the realms of history.
Regional lymph node status provides information regarding staging, local control, and prognostic outcomes in all cancers. This information was provided in breast cancer by axillary lymph node dissection (ALND). This changed with the development of sentinel lymph node biopsy (SLNB) [1, 2]. Sentinel lymph nodes (SLNs) are defined as the first lymph nodes receiving lymphatic drainage from the primary tumour and therefore the most likely to harbour metastatic cancer via lymphatic spread. SLNB is now the standard of care in patients with a clinically and radiologically clear axilla in early-stage breast cancer.
sentinel lymph node biopsy; axillary lymph node dissection; magnetic resonance imaging; ultrasmall paramagnetic iron oxide
Increasing numbers of patients with breast cancer are being treated with postmastectomy radiation therapy (PMRT). The author reviewed the literature to determine the clinical impact of this increasing use of PMRT in patients with breast cancer who desire implant-based breast reconstruction.
The author searched the MEDLINE database for articles on breast reconstruction and radiation therapy published between January 2008 and June 2011, and reviewed the abstracts of those articles to identify articles with information about the impact of radiation on implant-based breast reconstruction. This subgroup of articles was reviewed in detail.
Two-hundred eighty-five articles were identified. 19 papers were reviewed in detail. 8 papers provided level III evidence; one provided level I or II (n = 8) evidence from high-quality multicenter or single-center randomized controlled trials or prospective cohort studies. Two papers provided level IV evidence from case series and were included in the review because they offered a novel approach or perspective. The most recent studies find a significant need for unplanned or major corrective surgery in irradiated breasts reconstructed with implants. Although breast implant reconstruction in irradiated breasts is associated with high rates of complications; only a minority of patients require conversion to an autologous tissue flap.
Although the majority of patients who undergo implant-based reconstruction and receive radiation ultimately keep the implant reconstruction, patient surveys show that radiation has a significantly negative effect on patient satisfaction.
The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1–3, 4–9 and ≥10 positive axillary nodes). Methods: A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as ‘Radio + /ECE + ’, ‘Radio–/ECE + ’, ‘Radio + /ECE–’ or ‘Radio–/ECE–’ according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. Results: ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1–3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4–9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). Conclusion: In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1–3 or ≥10 positive axillary nodes. However, for patients with 4–9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.
breast neoplasms; ECE; PMRT; prognosis
At the moment, positive sentinel lymph node dissection (SLND) of the axilla is followed by axillary lymph node dissection (ALND) as standard of care. Recent data proves that omitting ALND after positive SLND in clinically lymph node-negative early stage breast cancer patients is feasible with low recurrence rates. The well known effect of radiotherapy to destroy occult tumor cells highly contributes to these results as a large extent of level I and II lymph nodes are unavoidably included in standard tangential radiation treatment fields. Reviewing the up to date published data on axillary lymph node treatment with radiotherapy, we hypothesize that full dosage coverage of level I and II of the axilla in early stage breast cancer will improve outcome and should be further evaluated.
Adjuvant treatment; Breast cancer; Curative radiotherapy; Sentinel lymph node
Androgen suppression treatment (AST) might increase the risk of cardiac morbidity in prostate cancer patients. Possible explanations were provided, however, they disregard the potential contribution of prophylactic radiotherapy to the mamillary regions (PMRT, prescribed to avoid gynecomastia).
We studied the exposure of the heart in a typical electron beam PMRT setting by evaluating computed tomography (CT) scans in 40 non-cancer patients (age 65 and 75 years in 50% each) and 17 prostate cancer patients. Five of the younger, 7 of the older and 4 of the cancer patients had significant cardiac disease.
The median distance between skin and outer heart contour decreased with age. In all three groups, patients with cardiac morbidity had smaller distances. When using the CT-determined PMRT beam energy, 10% of the younger, 15% of the older and none of the prostate cancer patients would receive approximately 50% of the prescription dose to a part of the heart (2 had no history of cardiac disease). When using the clinically rather than CT-determined beam energy, as often done in daily practice, an additional 12.5% of the non-cancer and 12% of the prostate cancer patients would be exposed to comparably high doses.
The present data provide preliminary evidence that PMRT might be a factor that contributes to cardiac side effects. Previous studies that established a relationship between AST and cardiac morbidity did not include information on delivery of PMRT.
To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy.
Patients and Methods
Patients with early-stage resected human epidermal growth factor receptor 2 (HER-2) –positive breast cancer (BC) were randomly assigned to doxorubicin (A) and cyclophosphamide (C), followed by weekly paclitaxel (T; AC-T-H or AC-TH-H). RT criteria (with or without nodal RT) were postlumpectomy breast or (optional) postmastectomy chest wall. RT of internal mammary nodes was prohibited. RT commenced within 5 weeks after T, concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms. Rates of cardiac events (CEs) with and without RT were compared within arms.
No significant differences among arms were found in incidence of acute skin reaction, pneumonitis, dyspnea, cough, dysphagia, or neutropenia. A significant difference occurred in incidence of leukopenia, with higher rates for AC-T-H versus AC-T (odds ratio = 1.89; 95% CI, 1.25 to 2.88). At a median follow-up of 3.7 years (range, 0 to 6.5 years), RT with H did not increase relative frequency of CEs regardless of treatment side. The cumulative incidence of CEs with AC-T-H was 2.7% with or without RT. With AC-TH-H, the cumulative incidence was 1.7% v 5.9% with or without RT, respectively.
Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs. Further follow-up is required to assess late AEs.
One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient.
In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery.
Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure.
When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer.