To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy (PMRT).
Locoregional control, disease-free survival, overall survival and treatment-related toxicities.
This guideline is based on a review of all meta-analyses, consensus statements and other guidelines published between 1966 and November 2002. Searches of MEDLINE and CANCERLIT for English-language randomized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously reviewed by the American Society of Clinical Oncology (ASCO) Health Services Research Committee panel in its published guideline. A nonsystematic review of the literature was continued through June 2003.
RecommendationsLocoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall).Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes.The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. These women should be offered the opportunity to participate in clinical trials of PMRT.Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes.Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear.PMRT should encompass the chest wall and the supraclavicular, infraclavicular and axillary apical lymph node areas.To reduce the risk of lymphedema, radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes.A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT cannot be made because of limited and inconsistent data.The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure, particularly to the cardiac and pulmonary structures.Common short-term side effects of PMRT, including fatigue and skin erythema, are generally tolerable and not dose-limiting. Severe long-term side effects, including lymphedema, cardiac and pulmonary toxicities, brachial plexopathy, rib fractures and secondary neoplasms, are relatively rare.The optimal sequencing of PMRT and systemic therapy is currently unclear. Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity.
The authors' original text was submitted for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 11 oncologists from across Canada. The final document was approved by the steering committee.
The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada.
This study was conducted to assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with four or more positive lymph nodes after postmastectomy radiotherapy (PMRT).
This retrospective study examined 605 breast cancer patients with four or more positive lymph nodes who underwent mastectomy. A total of 371 patients underwent PMRT. The prognostic value of the NLN count in patients with and without PMRT was analyzed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors.
The median follow-up was 54 months, and the overall 8-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 79.8%, 50.0%, 46.8%, and 57.9%, respectively. The optimal cut-off points for NLN count was 12. Univariate analysis showed that the number of NLNs, lymph node ratio (LNR) and pN stage predicted the LRFS of non-PMRT patients (p < 0.05 for all). Multivariate analysis showed that the number of NLNs was an independent prognostic factor affecting the LRFS, patients with a higher number of NLNs had a better LRFS (hazard ratio = 0.132, 95% confidence interval = 0.032-0.547, p =0.005). LNR and pN stage had no effect on LRFS. PMRT improved the LRFS (p < 0.001), DMFS (p = 0.018), DFS (p = 0.001), and OS (p = 0.008) of patients with 12 or fewer NLNs, but it did not any effect on survival of patients with more than 12 NLNs. PMRT improved the regional lymph node recurrence-free survival (p < 0.001) but not the chest wall recurrence-free survival (p = 0.221) in patients with 12 or fewer NLNs.
The number of NLNs can predict the survival of breast cancer patients with four or more positive lymph nodes after PMRT.
Electronic supplementary material
The online version of this article (doi:10.1186/s13014-014-0284-5) contains supplementary material, which is available to authorized users.
Breast cancer; Mastectomy; Negative lymph nodes; Radiotherapy
To explore the effects of postmastectomy radiotherapy (PMRT) on the locoregional failure-free survival (LRFFS) and overall survival (OS) of breast cancer patients under different tumor stages and with one to three positive axillary lymph nodes (ALNs).
We conducted a retrospective review of 527 patients with one to three positive lymph nodes who underwent modified radical or partial mastectomy and axillary dissection from January 2000 to December 2002. The patients were divided into the T1-T2 N1 and T3-T4 N1 groups. The effects of PMRT on the LRFFS and OS of these two patient groups were analyzed using SPSS 19.0, Pearson’s χ2-test, Kaplan-Meier method, and Cox proportional hazard model.
For T1-T2 N1 patients, no statistical significance was observed in the effects of PMRT on LRFFS [hazard ratio (HR)=0.726; 95% confidence interval (CI): 0.233-2.265; P=0.582] and OS (HR=0.914; 95% CI: 0.478-1.745; P=0.784) of the general patients. Extracapsular extension (ECE) and high histological grade were the risk factors for LRFFS and OS with statistical significance in multivariate analysis. Stratification analysis showed that PMRT statistically improved the clinical outcomes in high-risk patients [ECE (+), LRFFS: P=0.026, OS: P=0.007; histological grade III, LRFFS: P<0.001, OS: P=0.007] but not in low-risk patients [ECE (–), LRFFS: P=0.987, OS: P=0.502; histological grade I-II, LRFFS: P=0.816, OS: P=0.296]. For T3-T4 N1 patients, PMRT effectively improved the local control (HR=0.089; 95% CI: 0.210-0.378; P=0.001) of the general patients, whereas no statistical effect was observed on OS (HR=1.251; 95% CI: 0.597-2.622; P=0.552). Absence of estrogen receptors and progesterone receptors (ER/PR) (–) was an independent risk factor. Further stratification analysis indicated a statistical difference in LRFFS and OS between the high-risk patients with ER/PR (–) receiving PMRT and not receiving PMRT [ER/PR (–), LRFFS: P=0.046, OS: P=0.039]. However, PMRT had a beneficial effect on the reduction of locoregional recurrence (LRR) but not in total mortality [ER/PR (+), LRFFS: P<0.001, OS: P= 0.695] in T3-T4 N1 patients with ER/PR (+) who received endocrine therapy.
PMRT could reduce ECE (+), histological grade III-related LRR, and total mortality of T1-T2 N1 patients. T3-T4 N1 patients with ER/PR (–) could benefit from PMRT by improving LRFFS and OS. However, PMRT could only reduce LRR but failed to improve OS for T3-T4 N1 patients with ER/PR (+) who received endocrine therapy.
Breast cancer; positive lymph nodes; postmastectomy radiotherapy (PMRT); locoregional failure-free survival (LRFFS); overall survival (OS)
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
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.
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 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.
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
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
Purpose: To assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with positive axillary lymph nodes after mastectomy and its predictive value for radiotherapy efficacy of different breast cancer subtypes (BCS).
Methods: The records of 1,260 breast cancer patients with positive axillary lymph nodes who received mastectomy between January 1998 and December 2007 were reviewed. The prognostic impact and predictive value of the number of NLNs with respect to locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were analyzed.
Results: The median follow-up time was 58 months, and 444 patients (35.2%) received postmastectomy radiotherapy (PMRT). Univariate and multivariate Cox survival analysis indicated the number of NLNs was an independent prognostic factor of LRFS, DFS, and OS. Patients with a higher number of NLNs had better survival. PMRT improved the LRFS of patients with ≤ 8 NLNs ( p < 0.001), while failing to improve the LRFS of patients with > 8 NLNs (p = 0.075). In patients with luminal A subtype, PMRT improved the LRFS, DFS, and OS of patients with ≤ 8 NLNs, but in patients with > 8 NLNs only the LRFS was improved. For patients with luminal B subtype, PMRT only improved the LRFS of patients with ≤ 8 NLNs. The number of NLNs had no predictive value for the efficacy with PMRT in Her2+ and triple-negative subtypes.
Conclusions: The number of NLNs is a prognostic indicator in patients with node-positive breast cancer, and it can predict the efficacy of PMRT according to different BCS.
Breast cancer; mastectomy; radiotherapy; negative lymph nodes; prognosis
This retrospective study investigated the clinical value of post-mastectomy radiotherapy (PMRT) in female Chinese breast cancer patients aged 35 years or younger with positive axillary lymph nodes after mastectomy.
We performed an analysis of clinical pathological data from 221 female Chinese breast cancer patients aged 35 years or younger treated between 1998 and 2007. Patients were diagnosed with positive axillary lymph nodes and underwent mastectomy. PMRT was delivered to 92 patients.
The median follow-up was 61 months. The 5-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 84.1%, 65.2%, 61.4%, and 77.2%, respectively. Univariate survival analysis (P=0.003) and multivariate analysis (P<0.001) both suggested that PMRT is an independent prognostic factor of LRFS. PMRT positively affected LRFS (P=0.003), but had no significant impact on DMFS (P=0.429), DFS (P=0.146), and OS (P=0.750). PMRT improved LRFS (P=0.001), DFS (P=0.017), and OS (P=0.042) in patients with four or more positive nodes, but no survival benefit was observed in patients with one to three positive nodes (P>0.05).
PMRT can improve survival in breast cancer patients aged 35 years or younger with four or more positive nodes but not in those with one to three positive nodes.
breast cancer; radiation therapy; mastectomy; young age; locoregional recurrence
We sought to determine present-day loco-regional recurrence (LRR) rates to better understand the role of postmastectomy radiotherapy (PMRT) in women with 0 to 3 positive lymph nodes.
Clinical and pathologic factors were identified for 1019 patients with pT1 or pT2 tumors and 0 (n = 753), 1 (n = 176), 2 (n = 69), or 3 (n = 21) positive lymph nodes treated with mastectomy without PMRT during 1997 to 2002. Total LRR rates were calculated by Kaplan-Meier analysis and compared between subgroups by the log rank test.
After a median follow-up of 7.47 years, the overall 10-year LRR rate was 2.7%. The only independent predictor of LRR was younger age (P = 0.004). Patients ≤40 years old had a 10-year LRR rate of 11.3 vs. 1.5% for older patients (P < 0.0001). The 10-year rate of LRR in patients with 1 to 3 positive nodes was 4.3% (94.4% had systemic therapy), which was not significantly different from the 10-year risk of contralateral breast cancer development (6.5%; P > 0.5). Compared with the 10-year LRR rate among patients with node-negative disease (2.1%), patients with 1 positive node had a similar 10-year LRR risk (3.3%; P > 0.5), and patients with 2 positive nodes had a 10-year LRR risk of 7.9% (P = 0.0003). Patients with T2 tumors with 1 to 3 positive nodes had a 10-year LRR rate of 9.7%.
In patients with T1 and T2 breast cancer with 0 to 3 positive nodes, LRR rates after mastectomy are low, with the exception of patients ≤40 years old. The indications for PMRT in patients treated in the current era should be reexamined.
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
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
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.
Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II–III breast cancer.
Patients and Methods
We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA–IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival.
Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27).
Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy.
Radiation therapy; mastectomy; young age; neoadjuvant chemotherapy
The purpose of this study was to evaluate the brachial plexus (BP) dose of postmastectomy radiotherapy (PMRT) to the ipsilateral supraclavicular (ISCL) area, and report the characteristics of radiation-induced brachial plexus neuropathy (RIBPN).
The BP dose of 31 patients who received adjuvant PMRT to the ISCL area and chest wall using three-dimensional conformal radiotherapy (3DCRT) and the records of 3 patients with RIBPN were retrospectively analyzed based on the standardized Radiation Therapy Oncology Group-endorsed guidelines. The total dose to the ISCL area and chest wall was 50 Gy in 25 fractions.
Patients with a higher number of removed lymph nodes (RLNs) had a higher risk of RIBPN (hazard ratio [HR]: 1.189, 95% confidence interval [CI]: 1.005-1.406, p = 0.044). In 31 patients treated with 3DCRT, the mean dose to the BP without irradiation to the ISCL area was significantly less than that with irradiation to the ISCL area (0.97 ± 0.20 vs. 44.39 ± 4.13 Gy, t = 136.75, p <0.001). In the 3DCRT plans with irradiation to the ISCL area and chest wall, the maximum dose to the BP was negatively correlated with age (r = −0.40, p = 0.026), body mass index (BMI) (r = −0.44, p = 0.014), and body weight (r = −0.45, p = 0.011). Symptoms of the 3 patients with RIBPN occurred 37–65 months after radiotherapy, and included progressive upper extremity numbness, pain, and motor disturbance. After treatment, 1 patient was stable, and the other 2 patients’ symptoms worsened.
The incidence of RIBPN was higher in patients with a higher number of RLNs after PMRT. The dose to the BP is primarily from irradiation of the ISCL area, and is higher in slim and young patients. Prevention should be the main focus of managing RIBPN, and the BP should be considered an organ-at-risk when designing a radiotherapy plan for the ISCL area.
Breast cancer; Radiation therapy; Brachial plexus; Radiation-induced brachial plexus neuropathy
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.
Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2–16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7–12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37–3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.
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
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
To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease.
Patients and methods.
A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling.
With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI.
For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.
breast cancer; postmastectomy radiotherapy; overall survival; locoregional recurrence; lymphovascular invasion
We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt).
Medical records (1998–2007) were retrospectively reviewed for the population of interest. The Kaplan–Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr.
The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis–free survival (dmfs), and breast cancer–specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001).
Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs.
In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs.
Breast cancer; mastectomy; radiotherapy; locoregional recurrence; prognostic analysis
The authors studied the radiosensitization of breast cancer stem-like cells in vitro after treatment with the most commonly used statin, simvastatin, and examined the influence on local control after postmastectomy radiation among inflammatory breast cancer patients taking statins. This work provides new insight on combination regimens for breast cancer treatment and radiosensitization of this clinically radioresistant disease.
Reported rates of local failure after adjuvant radiation for women with inflammatory breast cancer (IBC) and triple-negative non-IBC are higher than those of women with receptor-expressing non-IBC. These high rates of locoregional recurrence are potentially influenced by the contribution of radioresistant cancer stem cells to these cancers. Statins have been shown to target stem cells and improve disease-free survival among IBC patients. We examined simvastatin radiosensitization of multiple subtypes of breast cancer cell lines in vitro in monolayer and mammosphere-based clonogenic assays and examined the therapeutic benefit of statin use on local control after postmastectomy radiation (PMRT) among IBC patients. We found that simvastatin radiosensitizes mammosphere-initiating cells (MICs) of IBC cell lines (MDA-IBC3, SUM149, SUM190) and of the metaplastic, non-IBC triple-negative receptor cell line (SUM159). However, simvastatin radioprotects MICs of non-IBC cell lines MCF-7 and SKBR3. In a retrospective clinical study of 519 IBC patients treated with PMRT, 53 patients used a statin. On univariate analysis, actuarial 3-year local recurrence-free survival (LRFS) was higher among statin users, and on multivariate analysis, triple negative breast cancer, absence of lymphatic invasion, neoadjuvant pathological tumor response to preoperative chemotherapy, and statin use were independently associated with higher LRFS. In conclusion, patients with IBC and triple-negative non-IBC breast cancer have the highest rates of local failure, and there are no available known radiosensitizers. We report significant improvement in local control after PMRT among statin users with IBC and significant radiosensitization across triple-negative and IBC cell lines of multiple subtypes using simvastatin. These data suggest that simvastatin should be justified as a radiosensitizing agent by a prospective clinical trial.
Statins; Inflammatory breast cancer; Local recurrence; Radiation
To examine the feasibility of volumetric modulated arc therapy (VMAT) for post mastectomy radiotherapy (PMRT).
Methods and materials
Fifteen PMRT patients previously treated at our clinic with helical tomotherapy (HT) were identified for the study. Planning target volumes (PTV) included the chest wall and regional lymph nodes. A systematic approach to constructing VMAT that met the clinical goals was devised. VMAT plans were then constructed for each patient and compared with HT plans with which they had been treated. The resulting plans were compared on the basis of PTV coverage; dose homogeneity index (DHI) and conformity index (CI); dose to organs at risk (OAR); tumor control probability (TCP), normal tissue complication probability (NTCP) and secondary cancer complication probability (SCCP); and treatment delivery time. Differences were tested for significance using the paired Student’s t-test.
Both modalities produced clinically acceptable PMRT plans. VMAT plans showed better CI (p < 0.01) and better OAR sparing at low doses than HT plans, particularly at doses less than 5 Gy. On the other hand, HT plans showed better DHI (p < 0.01) and showed better OAR sparing at higher doses. Both modalities achieved nearly 100% tumor control probability and approximately 1% NTCP in the lungs and heart. VMAT showed lower SCCP than HT (p < 0.01), though both plans showed higher SCCP values than conventional mixed beam (electron-photon) plans reported by our group previously. VMAT plans required 66.2% less time to deliver than HT.
Both VMAT and HT provide acceptable treatment plans for PMRT. Both techniques are currently utilized at our institution.
Volumetric modulated arc therapy; Helical tomotherapy; Post mastectomy