5-year Locoregional Recurrence Rate Research Articles

Impact of Postmastectomy Radiation on Locoregional Recurrence in Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated With Modern Systemic Therapy

Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonal therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with ≥2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered for PMRT.

Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

Prognostic Factors for Locoregional Recurrences in Colon Cancer

There is increased interest in locoregional recurrences of rectal cancer. Despite comparable locoregional recurrence rates in colon cancer, only a few studies on locoregional recurrences among colon cancer patients have been published. This study was designed to identify prognostic factors for locoregional recurrences among patients with colon cancer in the Netherlands. The study population was composed of patients who underwent radical surgical resections for invasive colon carcinoma, diagnosed in three regions of the Netherlands from 2000 to 2003. The Kaplan-Meier method was used to calculate 5-year locoregional recurrence rates (LRR). Conditional hazard rates were estimated by the life-table method. Multivariate Cox regression analyses were performed to identify prognostic factors and to calculate a Locoregional Recurrence Risk Score (LRRS). In total 127 of 2,282 patients developed locoregional recurrences within 5years (LRR 6.4%). The risk of developing a locoregional recurrence was highest at 0.5-1year after surgery. Patients with left-sided tumors, T3-T4 tumors, and positive lymph nodes and those who did not receive adjuvant chemotherapy were more likely to develop locoregional recurrences. Four risk groups based on the LRRS were defined. Five-year LRR was 2.5% for the very low-risk group and 25.1% for the high-risk group. Although the locoregional recurrence rate in this study was relatively low, it remains a considerable problem. Identifying individual patients who might benefit from adjuvant chemotherapy may reduce the locoregional recurrence rate.

Adherence to guideline excision margins in head and neck melanoma: the influence on 5-year survival and loco-regional recurrence

Guidelines for the management of cutaneous melanoma suggest wide local excision of increasing margins for increasing Breslow thickness of the primary neoplasm. These guidelines are based on randomized controlled trial data from limb and trunk melanoma studies. We performed retrospective analysis of our institution's head and neck melanoma database to investigate the effect of narrow excision margins on survival and loco-regional recurrence. We identified 101 patients with node-negative head and neck melanoma from 1993 to 2001 who had prospectively gathered data. The overall 5-year loco-regional recurrence rate (LR) was 37%. The overall 5-year melanoma-specific survival rate (5y.s.) was 70%. When guidelines were followed (n = 36), LR was 19% and 5y.s. was 89%. When guidelines were not followed (n = 65), LR was 46% and 5y.s. was 60%. On univariate analysis, we found scalp location (p < 0.001), male gender (p < 0.025), advanced tumour T stage (p < 0.005) and non-adherence to guidelines (p < 0.003) were significantly associated with poorer 5y.s., whilst scalp location (p < 0.004), advanced tumour T stage (p < 0.030) and non-adherence to guidelines (p < 0.010) were significantly associated with greater LR. On multivariate analysis, only scalp location (p < 0.001; p < 0.001) and advanced tumour T stage (p < 0.020; p < 0.014) remained significant predictors of 5y.s. and LR. We conclude it is often impossible to perform excision margins as recommended in published guidelines for cutaneous melanoma in the head and neck, given functional and aesthetic constraints. While such margins should be adhered to where possible, adherence is not the major factor in long-term recurrence and survival (level of evidence: IV).

Postmastectomy chest wall radiotherapy with single low-energy electron beam: An assessment of outcome and prognostic factors

This study aimed to evaluate the outcome of patients who had received postmastectomy chest wall radiotherapy using a single electron beam, and to identify the relevant factors that influenced prognosis. The medical records of patients with breast cancer treated with postmastectomy radiotherapy from January 2000 to December 2004 were retrospectively analyzed (n = 328). Two hundred seventy-one (82.6%) patients were staged as (tumor-nodes-metastasis [TNM]) T3-4, any N, M0; or T1-2, N2-3, M0, and 57 (17.4%) patients were staged as T1-2, N1, M0. All patients received chest wall radiation with a 6-10 MeV electron beam. In addition, 327 patients (99.7%) received supraclavicular node radiation, 67 (20.4%) axillary radiation, and 35 (10.7%) internal mammary chain (IMC) radiation. Chemotherapy with anthracycline and taxane was given to 323 patients (98.5%). Of patients with positive hormone receptor, 183 (82.8%) received hormone therapy and 8 patients with negative and 3 patients with unknown hormone receptor received hormone therapy. Locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences assessed by log-rank test. The median follow-up time was 78 months (range, 5-123 months) for patients who remained alive. The 5-year LRR, DM, disease-free survival and OS rates were 5.9%, 26.2%, 72.5%, and 83.1%, respectively. LRR occurred in 1 or more sites in 21 patients. The 5-year recurrence rates in the chest wall, supraclavicular node, axilla, and internal mammary chain were 1.9%, 2.3%, 2.9%, and 0%, respectively. In multivariate analysis, hormone therapy was the only independent favorable prognostic factor for LRR (P = .017). LRR was significantly associated with DM and OS. The 5-year DM rate was 82.9% and 22.7% (P < .0001) and the 5-year OS rate was 52.8% and 84.7% (P < .0001) for patients with or without LRR. The treatment-related toxicity was low, with the incidence of symptomatic pneumonitis being 0.3%. Breast cancer patients can be treated with postmastectomy single electron beam radiotherapy with excellent local control and low toxicity.

Molecular Class as a Predictor of Locoregional and Distant Recurrence in the Neoadjuvant Setting for Breast Cancer

Background: The molecular subtype by hormone receptor status predicts recurrence in the adjuvant setting. Here, we report recurrence patterns by molecular subtype following neoadjuvant chemotherapy (NACT) to identify subgroups prone to recurrence. Materials and Methods: We retrospectively analyzed 331 patients receiving NACT plus lumpectomy and whole breast radiation therapy (RT) (n = 155), or mastectomy with (n = 122) or without (n = 50) adjuvant RT. Tumors were classified by immunohistochemical (IHC) surrogate markers into luminal A (strong ER+/PR+; HER2–), luminal B (weak-to-moderate ER+/PR+; HER2–), HER2 (HER2+), and triple-negative/basal subtypes. Results: The median follow-up was 43 months (range 10–104). The 5-year disease-free survival (DFS) was 71.4, 70.1, 70.4, and 62.1% for luminal A, luminal B, HER2, and basal subtypes, respectively. The 5-year distant recurrence rates were 25.8, 28.7, 28.7, and 35.2%. The 5-year locoregional recurrence rates were 3.8, 1.6, 1.3, and 4.2%. Molecular class (p = 0.003) and pathologic complete response (pCR; p = 0.004) predicted distant recurrence, DFS, and overall survival (OS). Only the omission of adjuvant RT following mastectomy (p = 0.006) predicted locoregional recurrence. Conclusions: IHC subclassification and pCR predict distant failure, DFS, and OS in the neoadjuvant setting. While not predictive of locoregional recurrence, the total number of events were small. More work is needed to define if molecular class can predict patients at risk for locoregional recurrence.

Is Breast Conservation Therapy Superior to Mastectomy for Women With Triple-Negative Breast Cancers?

In the article that accompanies this editorial, Abdulkarim et al report that women with T1-2N0 triple-negative breast cancers (TNBCs) treated with breast-conserving surgery followed by radiation therapy had significantly better locoregional control compared with matched women treated with total mastectomy after a median follow-up of 7.8 years (P .027). Should this observation change practice guidelines? There has been much attention focused on TNBCs since the first identification of basal-like cancers using microarray expression profiling studies in 2005. TNBCs lack the expression of estrogen and progesterone receptors and do not overexpress human epidermal growth factor receptor 2. There is a significant overlap between TNBCs, which are defined by immunohistochemistry, and basaloidlike tumors, which are identified from gene expression profiling, such that those two entities are frequently considered synonymous from a clinical perspective. TNBCs have a poor prognosis and do not respond to therapy directed at known breast cancer growth factor targets, including hormonal therapy and trastuzumab. TNBCs are fast-growing tumors, usually have a high histologic grade, and tend to metastasize earlier compared with breast cancers that express hormone receptors. The predominant sites of metastases for TNBCs differ from the luminal subtype. They are more frequently nodenegative and spread, in 70% of patients, to the lung and brain, whereas luminal cancers tend to metastasize, in 70% of patients, to the bone and liver. TNBC tumors seem to be more sensitive to chemotherapy, and although there is a sharp decrease in survival early after diagnosis, survival plateaus after 8 to 10 years. Although poorer survival and metastatic outcomes of TNBCs are well known, local or regional evolution characteristics of TNBCs remain controversial. Publications that assessed the value of TNBCs as an independent prognostic factor for locoregional recurrence showed mixed results; some articles reported an increased risk of locoregional recurrence, and other articles reported no increase in the locoregional recurrence risk compared with the luminal A phenotype. Most of these series included a small number of TNBCs mixed with other breast cancer subtypes, and the study by Abdulkarim et al adds appreciably to this literature by reporting exclusively on TNBCs. The authors identified 768 patients with TNBCs referred to the sole regional cancer center in northern Alberta, Canada, between 1998 and 2008. As such, this series approximated a population-based experience with its strength and weaknesses. In one way, the series represented a single-institution retrospective study; in contrast, it represented the largest series of TNBCs reported to date, without the drawback of patient selection associated with clinical trials. The investigators analyzed locoregional recurrence and survival outcomes by the type of initial local therapy and found that patients treated with breast-conserving surgery followed by adjuvant radiotherapy had significantly lower rates of locoregional recurrence compared with patients treated with mastectomy alone. An important and valuable analytic approach was to identify a subset of 195 pairs of patients with T1-2N0 TNBCs by matching for T stage individuals treated with breast-conserving surgery followed by adjuvant radiotherapy with patients treated by mastectomy. Among patients with T1-2N0 TNBCs, individuals initially treated with breast-conserving surgery followed by adjuvant radiotherapy had a 5-year actuarial locoregional recurrence rate of 4% compared with 10% after mastectomy (P .027). It would have been useful to have had specific information on the quality of the matching for important prognostic factors such as including the number of nodes removed, margin width/status, BRCA status, type of chemotherapy used, and duration of follow-up between groups; however, these parameters can be inferred to be reasonably equivalent on the basis of the data presented in Table 4 and Figure 2B. As listed in the table and figure, both cohorts had relatively similar clinicopathologic characteristics in regards to age, tumor grade, lymphovascular invasion status, and delivery of adjuvant chemotherapy and had the same proportions of patients accrued over time. Although there was the possibility that confounding factors may not have been perfectly balanced between groups, the data of Abdulkarim et al, together with those of other reports, suggested that local recurrence is an issue and radiotherapy may decrease this risk. There are three messages to take from this study. First, the paradigm in breast cancer that breast-conserving surgery followed by radiation therapy is equivalent to mastectomy alone may not apply to all patients. TNBCs are rapidly growing and locally aggressive cancers that may represent a limit to this principle. Obviously, the role of adjuvant radiotherapy in this population requires additional study. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L S

Ten-Year Locoregional Recurrence Risks in Women With Nodal Micrometastatic Breast Cancer Staged With Axillary Dissection

To compare the locoregional recurrence (LRR) rates in patients with nodal mirometastases (pNmic) with those in patients with node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; and to evaluate the LRR rates according to locoregional treatment of pNmic disease. The subjects were 9,616 women diagnosed between 1989 and 1999 with Stage pT1-T2, pN0, pNmic, or pNmac, M0 breast cancer. All women had undergone axillary dissection. The Kaplan-Meier local recurrence, regional recurrence, and LRR rates were compared among those with pN0 (n=7,977), pNmic (n=490) and pNmac (n=1,149) and according to locoregional treatment. Multivariate analysis was performed to identify the significant factors associated with LRR. The median follow-up was 11 years. The 10-year Kaplan-Meier recurrence rate in the pN0, pNmic, and pNmac cohorts was 6.1%, 6.8%, and 8.7% for local recurrence; 3.1%, 6.2%, and 10.3% for regional recurrence; and 8.0%, 11.6%, and 15.2% for LRR, respectively (all p<.001). In the pNmic patients, the 10-year regional recurrence rate was 6.4% with breast-conserving surgery plus breast radiotherapy (RT), 5.4% with breast-conserving surgery plus locoregional RT, 4.6% with mastectomy alone, 11.1% with mastectomy plus chest wall RT, and 10.7% with mastectomy plus locoregional RT. In patients with pNmic disease and age<45 years, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease, the 10-year LRR rates were 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with greater LRR than Stage pN0 (hazard ratio [HR], 1.6; p=.002). On multivariate analysis of pNmic patients only, age<45 years was associated with significantly greater LRR (HR, 1.9; p=.03), and trends for greater LRR were observed with a nodal ratio>0.25 (HR, 2.0; p=.07) and lymphovascular invasion (HR, 1.7; p=.07). Women with pNmic had a greater risk of LRR than those with pN0 disease. Patients with pNmic in association with young age, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease experienced 10-year LRR rates of ∼15-20%, warranting consideration of locoregional RT.

Cancers du sein de stade II-IIIA : la radiothérapie exclusive est-elle une option en cas de réponse clinique complète à la chimiothérapie néoadjuvante ?

Purpose To determine whether exclusive radiotherapy could be a therapeutic option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC). Patients and methods Between 1985 and 1999, 1477 patients received néoadjuvante chemotherapy for early breast cancer considered to be too large for primary conservative surgery. Of 165 patients with complete clinical response, 65 were treated by breast surgery (with radiotherapy) and 100 by exclusive radiotherapy. Results The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the exclusive radiotherapy group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91 and 77% in the no surgery group and 82 and 79% in the surgery group, respectively ( P = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31 vs. 17% at 10 years; P = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different ( P = 0.45, 10-year LRR: 21 in surgery vs. 26% in exclusive radiotherapy). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities. Conclusion Surgery is a key component of locoregional treatment for breast cancers that achieved complete clinical response to neoadjuvant chemotherapy.

Prognostic factors for skin-involved inflammatory and non-inflammatory breast cancer

Objective To analyze the prognostic factors and the role of postmastectomy radiotherapy (PMRT) in skin-involved breast cancer.Methods Fifty-three skin-involved breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed.Ten patients had inflammatory breast cancer (IBC).Of the 43 non-inflammatory breast cancer (NIBC) patients, 19(36%) had clinical signs of skin involvement and 24(45%) had pathological skin infiltration without clinical signs.Thirty-three patients (62%) received PMRT with a median dose of 50 Gy, 45 received chemotherapy and 27 received hormone therapy.Results The median follow up time for alive patients was 42 (7 -83) months.The overall 5-year locoregional recurrence (LRR),disease-free survival (DFS) and overall survival (OS) rates were 18%,45% and 64%.Patients with NIBC had a significantly better 5-year DFS (49% vs.30% ,χ2=4.29,P=0.038) and OS (71% vs.37% ,χ2=5.92,P=0.015) than those with IBC.In patients with NIBC, those with primary tumor ≤5 cm had a lower 5-year LRR (11% vs.33% ,χ2= 3.75 ,P =0.053) and a higher 5-year OS (90% vs.38% ,χ2=4.44,P=0.035) as compared to those >5 cm.No significant difference in terms of LRR, DFS or OS was observed between patients with clinical signs of skin involvement and those without.Patients with 0 - 3 positive nodes had an improved 5-year DFS (80% vs.29%, χ2= 6.71, P =0.010) and OS (93% vs.52% ,χ2=6.00,P=0.014) than those with ≥4 positive nodes.Patients with Rec + / Her2 - had a lower5 - year LRR (7 % vs.3 4 % , χ2= 5.70, P= 0.017) and a higher DFS (54% vs.32% ,χ2=8.82 ,P =0.003) than those with triple-negative or Her2 +.There was no significant difference in 5-year LRR (12% vs.30%, χ2= 2.45, P = 0.118) between patients with PMRT and without PMRT.However, the 5-year chest wall recurrence rate was 0% and 50% (χ2= 9.15 ,P =0.002) for patients with chest wall bolus dose > 20 Gy and 20 Gy.Conclusions Skin-involved breast cancer is a heterogeneous group of diseases.Patients with NIBC, small tumor (≤5 cm), less positive nodes (0 -3) or rec +/Her2-have favorable prognosis.Patients with pathologically proven skin involvement without clinical signs have similar prognosis to those with clinical signs.PMRT with chest wall bolus dose >20 Gy is recommended. Key words: Breast neoplasms/radiotherapy; Radiotherapy,postoperation; Skin-involvement; Prognosis

Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy

To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy. The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS). 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS. ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

Outcomes of Node-Negative Breast Cancer 5 Centimeters and Larger Treated With and Without Postmastectomy Radiotherapy

The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.0-cm tumors treated with mastectomy, stratified by PMRT use. Between January 1, 1989 and December 31, 2000, the British Columbia provincial database yielded 100 node-negative patients with tumors ≥ 5 cm of 19,846 nonmetastatic breast cancer patients (0.5%). Of these 100 patients, 44 (44%) had received adjuvant PMRT. The PMRT group contained significantly more pT3 >5-cm cases (p = 0.001) and margin-positive cases (p = .03). With a median follow-up of 10 years, the cumulative 10-year LRR rate was 2.3% (95% confidence interval, 0.2-10.5) in the PMRT group vs. 8.9% (95% confidence interval, 3.2-18.2) in the no-PMRT group (p = .2). Regarding LRR in the no-PMRT group, all patients had Grade 3 histologic features (LRR 17%, 5 of 29) and had not received hormonal therapy (LRR 15%, 5 of 34). The 10-year breast cancer-specific survival rate was 85.8% (95% confidence interval 71.0-93.4) in the PMRT group vs. 74.6% (95% confidence interval 59.9-84.5) in the no-PMRT group (p = .2). On multivariate analysis, adjusted for the prognostic and predictive variables, PMRT did not significantly improve the LRR or breast cancer-specific survival rates. The present study demonstrated a low LRR rate for node-negative breast cancer ≥ 5 cm. Our results indicate that PMRT should be considered for Grade 3 histologic features and patients not undergoing hormonal therapy.

Is Radiotherapy an Option for Early Breast Cancers With Complete Clinical Response After Neoadjuvant Chemotherapy?

To determine whether the exclusive use of radiotherapy (ERT) could be a treatment option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancer (EBC). Between 1985 and 1999, 1,477 patients received NCT for EBC considered too large for primary conservative surgery. Of 165 patients with cCR, 65 patients were treated with breast surgery (with radiotherapy) and 100 patients were treated with ERT. The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survival rates. Five-year and 10-year overall survival rates were 91% and 77% in the no-surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a nonsignificant trend toward higher locoregional recurrence rates (LRR) was observed in the no-surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac, or pulmonary toxicities. Surgery is a key component of locoregional treatment for breast cancers that achieved cCR to NCT.

Present-day locoregional control in patients with t1 or t2 breast cancer with 0 and 1 to 3 positive lymph nodes after mastectomy without radiotherapy.

We sought to determine present-day locoregional 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 7.47years, the overall 10-year LRR rate was 2.7%. The only independent predictor of LRR was younger age (P=0.004). Patients ≤40years 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 ≤40years old. The indications for PMRT in patients treated in the current era should be reexamined.

Is Exclusive Radiotherapy an Option for Early Breast Cancers with Complete Clinical Response after Neoadjuvant Chemotherapy?

Abstract Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC).Patients and methods: Between 1985 and 1999, 1477 patients received NCT for EBC considered to be too large for primary conservative surgery. Of 165 patients with cCR, 65 were treated by breast surgery (with radiotherapy) and 100 by ERT.Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91% and 77% in the no surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities.Conclusion: Omission of breast surgery in patients who achieved cCR to NCT was not associated with an increased risk of distant metastases or death. However a trend towards an increased risk of locoregional recurrence was observed in the ERT group. Imaging modalities appear to be essential to monitor chemotherapy response and possibly select patients in whom ERT can be proposed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4108.

Tumour Aromatase Expression, a Prognostic for Local Control in Young Breast Cancer Patients after Breast-Conserving Treatment?

Abstract Introduction: To determine whether the levels of expression of 17 candidate genes were associated with locoregional control after breast conserving treatments of early-stage breast cancers in young, premenopausal women.Methods: Gene expression was measured using RT-PCR in the breast tumors of a series of 53 young (≤40 years), premenopausal patients. All treatments consisted in primary breast conserving surgery followed by whole-breast radiotherapy (+/- regional lymph nodes) with or without systemic treatments (chemotherapy +/- hormone-therapy). The median follow-up was 10 years.Results: The 10-year locoregional recurrence rate was 70% (95% CI 57%-87%). In univariate analysis, no clinical/pathological prognostic factors were found to be significantly associated with a decreased loco-regional control. Expression of three genes was found to be significantly associated with an increased loco-regional recurrence rate: low estrogen receptor beta, low aromatase, high GATA3. Two others were associated with only a trend (p&amp;lt;0.10): low HER1 and SKP2. In multivariate analysis only the absence of aromatase was significantly associated with an increased loco-regional recurrence rate (p=0.003, Relative Risk=0.49 95% CI [0.29-0.82]).Conclusions: Recent data give credit to the fact that breast cancer in young women is a distinct biological entity driven by special oncogenic pathways. Our results highlight the role of estrogen signalling pathways (mainly CYP19/aromatase, GATA3 and ERβ) in the risk of locoregional recurrence of breast cancer in young women. Confirmation in larger prospective studies are needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6035.

Postmastectomy radiotherapy in moderate-and high-risk elderly breast cancer patients

To analyze the role of postmastectomy radiotherapy (PMRT) in moderate- and high-risk elderly breast cancer patients. The clinicopathological data of 874 breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed. The T1-2N1 patients were defined as moderate- risk (IR) group, and T3-4 and/or N2-3 cases as high-risk (HR) group. The locoregional recurrence (LRR) and overall survival (OS) rates were calculated and compared according to different age groups and radiotherapy status. Kaplan-Meier method and Log-rank test was used for calculation and comparison of the survival curves of different patient groups. The median follow up time was 47 months. 108 (12.4%) patients were > or = 65 years. For patients who were < 65 and > or = 65 years, 18.1% and 15.3% received PMRT in the IR group, and 82.7% and 52.2% received PMRT in the HR group, respectively. For patients > or = 65 years, the 5-year LRR rates were 0% and 14.2% (P = 0.242) and 5-year OS rates were 100% and 75.2% (P = 0.159) for the PMRT-IR and non-PMRT-IR groups, respectively. The 5-year LRR rates were 0% and 14.1% (P = 0.061), 5-year OS rates were 84.6% and 77.4% (P = 0.597) for the PMRT-HR and non-PMRT-HR groups, respectively. For patients < 65 years, the 5-year LRR rates were 0% and 9.9% (P = 0.035) and 5-year OS rates were 87.0% and 82.1% (P = 0.739) for the PMRT-IR and non-PMRT-groups, respectively. The 5-year LRR rates were 7.2% and 26.1% (P = 0.000), 5-year OS rates were 79.2% and 57.7% (P = 0.000) for the PMRT-HR and non-PMRT-HR groups, respectively. With the increasing of age, there is a trend of decreasing use of postmastectomy radiotherapy in high-risk breast cancer patients. Postmastectomy radiotherapy can improve the locoregional control for high-risk patients and maybe considered even for those who are > or = 65 years.

Chest Wall Radiotherapy: Middle Ground for Treatment of Patients With One to Three Positive Lymph Nodes After Mastectomy

To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) with or without the regional lymphatics. We retrospectively analyzed 238 patients with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Massachusetts General Hospital between 1990 and 2004. The estimates of locoregional recurrence (LRR), disease-free survival (DFS), and overall survival were analyzed according to the delivery of radiotherapy and multiple prognostic factors. LRR and DFS were significantly improved by postmastectomy radiotherapy (PMRT), with a 5- and 10-year LRR rate without PMRT of 6% and 11%, respectively and, with PMRT, of 0% at both 5 and 10 years (p = .02). The 5- and 10-year DFS rate without PMRT was 85% and 75%, respectively, and, with PMRT, was 93% at both 5 and 10 years (p = .03). A similar benefit was found for patients treated with RT to the CW alone. The LRR, DFS, and overall survival rate for patients treated to the CW only was 0%, 96%, and 95% at 10 years, respectively. Our data suggest that adjuvant PMRT to the CW alone provides excellent disease control for patients with breast cancer <5 cm with one to three positive lymph nodes.

Ten-Year Recurrence Rates in Young Women With Breast Cancer by Locoregional Treatment Approach

Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach.

Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results

Studies of outcome in patients with medullary thyroid carcinoma require long follow-ups to accrue enough cancer-specific events. Owing to time-dependent changes in diagnosis and therapy, long observation periods render studies susceptible to 'time bias' which can yield spurious results. This study was designed to investigate cancer-specific event rates after initial neck resection in contemporaneous patients recruited within less than a decade. Institutional cohort study of 128 consecutive patients who underwent compartment-oriented neck surgery between 1994 and 2002 at a tertiary surgical center for hitherto untreated medullary thyroid carcinoma. The Kaplan-Meier method was used in conjunction with the log-rank test for analysis of time-dependent outcomes. Follow-up was available for 120 patients (94%) including 63 rearranged during transfection (RET) carriers. There were six locoregional recurrences in the 110 patients with clear surgical margins at initial neck resection, and 12 cancer-specific deaths in the 120 patients with available follow-up. On Kaplan-Meier analysis, most clinicopathological variables were significantly associated with recurrence-free survival and cancer-specific survival. Within the median observation period of 64.5 months, patients with node-negative tumors did not develop locoregional recurrence or die from their malignancies. The low event rates precluded multivariate analyses with all clinicopathological variables. With our extensive surgical approach, median recurrence-free survival and cancer-specific survival at 5 years were 95.2 and 89.3% respectively. Compared with literature data, our 5-year locoregional recurrence rate of 4.8% appeared very favorable, and our 5-year cancer-specific mortality rate of 10.7% was among the lowest ever reported. The growing proportion of localized medullary thyroid carcinomas among contemporaneous patients can be expected to ultimately lower the event rates, complicating future studies of outcome.