Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: Implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation

PURPOSE: To compare rates of locoregional recurrence (LRR) after mastectomy, doxorubicin-based chemotherapy, and radiation with those of patients receiving mastectomy and doxorubicin-based chemotherapy without radiation and to determine predictors of LRR after postmastectomy radiation. METHODS: Kaplan-Meier freedom-from-LRR rates were calculated for 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five single-institution clinical trials. The LRR rates in these patients were compared to previously reported rates in 1031 patients treated without radiation in the same trials. RESULTS: Median follow-up was 14 years. Irradiated patients had significantly less favorable prognostic factors for LRR than did unirradiated patients. Despite this, in all subsets of node-positive patients, postmastectomy radiation led to lower rates of LRR. This included patients with T1 or T2 tumors and one to three positive nodes (10-year LRR rates of 3% vs. 13%, p = 0.003). Multivariate analysis of LRR for patients with this stage of disease revealed that no radiation, close/positive margins, gross extracapsular extension, and dissection of <10 nodes predicted for increased LRR (hazard ratios 6.25, 4.61, 3.27, and 2.66, respectively). Significant predictors of LRR for patients treated with postmastectomy radiation were higher number and >or=20% positive nodes, larger tumor size, lymphovascular space invasion, and estrogen receptor (ER)-negative disease. Recursive partitioning analysis revealed ER-negative status to be the most powerful discriminator of LRR in irradiated patients. CONCLUSIONS: Postmastectomy radiation decreases LRR for patients with breast cancer, including those with Stage II breast cancer and one to three positive lymph nodes.     

Locoregional recurrence risks in elderly breast cancer patients treated with mastectomy without adjuvant radiotherapy

This study examined tumour and treatment characteristics in elderly women treated with mastectomy without radiotherapy and compared their outcomes to younger counterparts. Data were analysed for 2362 women aged 50 years and older referred to the British Columbia Cancer Agency, Canada between 1989 and 1997. The women had invasive T1-4, N0-N3, M0 breast cancer treated with mastectomy without adjuvant radiotherapy. Clinical characteristics and patient outcomes were compared between two age cohorts: 50-69 (n = 1423) and 70+ years (n = 939). Median follow-up was 8.3 years. Tumours > 5 cm were present in 5% of women aged 50-69 and 3.5% of women aged 70+, respectively. The distribution of nodal stage was similar in the two age cohorts but older women were more likely to have fewer axillary nodes removed (P = 0.009). Fewer women aged 70+ had grade III histology (P = 0.002) and estrogen receptor (ER)-negative status (P < 0.001). The rates of systemic therapy use were comparable in the two age groups. With tumours > 5 cm, locoregional recurrence (LRR) were 13.7% and 30.0% in women aged 50-69 and 70+, respectively. With 1-3 positive nodes (N+), LRR were 14.8% and 13.0% in women aged 50-69 and 70+. In the presence of 4 N+, LRR were 16.8% and 30.8% in women aged 50-69 and 70+. On multivariate analysis, age was not significantly associated with LRR (P = 0.62). Independent prognostic factors for LRR were grade III histology, lymphovascular invasion and positive nodal status. This study suggests that despite more favourable tumour characteristics and comparable systemic therapy use, women aged 70+ years have similar or higher postmastectomy LRR risks compared to younger women. Chronologic age alone should not preclude these women from consideration of adjuvant radiotherapy.     

Locoregional recurrence following nipple-sparing mastectomy with immediate breast reconstruction: Patterns and prognostic significance

IntroductionThere are limited available data on the prognostic implications of locoregional recurrence (LRR) after nipple-sparing mastectomy (NSM) and immediate reconstruction. In this study, we investigated the patterns and prognosis associated with LRR following this treatment approach for breast cancer.MethodsA total of 1696 patients with primary breast cancer who underwent NSM with immediate reconstruction from March 2003 to December 2016 were retrospectively analyzed. Post-recurrence disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic factors associated with the DFS and DMFS.ResultsAfter a median follow-up period of 84 months, we identified 172 patients (10.1%) with an LRR as the first event. The 5-year post-recurrence DFS rates for the nipple-areola complex recurrence (NCR), skin or subcutaneous recurrence/chest wall recurrence (SCR/CWR), and regional recurrence (RR) groups were 89.1%, 73%, and 59.4%, respectively (P = 0.009), and the 5-year post-recurrence DMFS rates for the NCR, SCR/CWR, and RR groups were 96%, 82.8%, and 59.7%, respectively (P < 0.001). In multivariate analysis, a time to LRR ≤2 years (P = 0.016) and the site of LRR (P = 0.022) were significantly associated with the post-recurrence DFS.ConclusionsNCR is more likely to be detected as a non-invasive recurrence and is associated with more favorable overall outcomes than other LRR types. The interval to LRR and its site of onset seem to be associated with the prognostic outcomes.     

Locoregional failure rates in patients with involved axillary nodes after mastectomy and systemic therapy.

Published series vary substantially in describing the incidence of locoregional failure after mastectomy among patients with involved axillary lymph nodes who receive systemic therapy. There are few data on such risks with regards to particular patient subsets (such as those defined by combinations of tumor size and nodal status). This article reviews the available data on these subjects as well as problems in their interpretation and clinical use.     

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.     

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

PURPOSE: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. METHODS AND MATERIALS: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. RESULTS: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. CONCLUSIONS: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy.     

Locoregional recurrence risk factors in breast cancer patients with positive axillary lymph nodes and the impact of postmastectomy radiotherapy

Background

Locoregional recurrence (LRR) after mastectomy reduces the patient’s quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps establish locoregional control and reduces LRR in patients with ≥4 metastatic nodes. However, in patients with 1–3 metastatic nodes, the incidence of LRR and the role of PMRT have been the subject of substantial controversy. This study assessed the risk factors for LRR and the efficacy of PMRT in Japanese breast cancer patients with metastatic nodes.

Methods

This study analyzed 789 cases of invasive breast carcinoma with metastatic nodes from 1998 to 2008. We divided the study population into 4 groups: 1–3 positive nodes with/without chemotherapy and ≥4 positive nodes with/without chemotherapy. Risk factors for LRR were identified and the relationship between LRR and PMRT was analyzed.

Results

During the median follow-up of 59.6 months, 61 (7.7%) patients experienced LRR. In patients who received chemotherapy, independent LRR risk factors were high nuclear grade, severe lymphatic invasion, vascular invasion, and progesterone receptor-negative status in patients with 1–3 positive nodes, and severe lymphatic invasion and estrogen receptor-negative status in patients with ≥4 nodes. Although patients treated with PMRT had good outcomes, there was no significant difference, and PMRT did not significantly improve the outcome of the patients with all risk factors.

Conclusions

With systemic therapy and adequate dissection, PMRT by itself was of limited value in establishing locoregional control. The indication for PMRT in patients with 1–3 positive nodes remains controversial.     

Low locoregional recurrence rates in patients treated after 2000 with doxorubicin based chemotherapy, modified radical mastectomy, and post-mastectomy radiation

Purpose

To determine the rate of locoregional recurrence (LRR) associated with modern tri-modality therapy.

Methods

We retrospectively reviewed data from 291 consecutive PMRT patients treated from 1999 to 2001. These patients were compared to an historical group of 313 patients treated from 1979 to 1988 who had fluoroscopic simulation and contour-generated 2D planning. 1999-2001 spans the adoption of CT simulators for breast radiation therapy and a comparison was made between patients simulated before and after the implementation of CT simulation. Five-year actuarial rates for LRR, distal metastasis (DM), and overall survival (OS) between the pre and post CT simulation cohorts were compared as well.

Results

Compared to a 2D planned historic control, the combined contemporary patients had improved outcomes at 5 years for all endpoints studied; LRR 3.0% vs. 11.5%, DM 29.2% vs. 39.2%, and OS 79.2% vs. 70.6% (p = 0.0004, 0.0052, 0.0012, respectively). Significant factors in a multivariate analysis for LRR were: advanced T-stage (RR = 2.14, CI = 1.11-4.11, p = 0.023), and percent positive nodes (RR = 1.01, CI = 1.00-1.02, p = 0.012). The comparison of the pre and post CT-simulated PMRT patients (1999-2001) found no significant difference in any endpoint.

Conclusions

The rate of locoregional control for PMRT patients treated with modern radiotherapy is outstanding and has improved significantly compared to historical controls.     

Ⅰ期、Ⅱ期乳腺癌术后局部复发的放疗及预后

目的：探讨乳腺癌术后局部区域复发的规律和再放疗的预后。方法：回顾分析45例Ⅰ期、Ⅱ期乳腺癌术后局部区域复发的情况以及复发后放疗的预后。26例采用局部野放疗，19例采用扩大野放疗。结果：T2及腋窝淋巴结转移数≥4枚或≥20％的病例占复发病例的73％。复发的部位依次为锁骨上、多部位、胸壁、腋窝、内乳。复发后2a生存率40％、无瘤生存率24．4％，2次局部区域复发率31％，术后2a以上复发的2a生存率64％，2a以下29％。首次复发累及多部位生存率18．2％，较单一锁骨上(47．4％)及胸壁(30％)低，累及锁骨上局部复发率高于胸壁，远处转移率低于胸壁，2次局部复发胸壁最高达57％，照射野采用广泛野的局部复发率低于采用局部野。结论：对Ⅰ期、Ⅱ期乳腺癌中腋窝淋巴结阳性≥4枚或≥20％的病例应常规行术后放疗，对术后局部区域复发的病例应采用包括胸壁及锁骨上下大范围照射。     

Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapy

BACKGROUND: The goal of the current study was to define the clinical features and outcome of recurrent osteosarcoma (OS) in children and young adults initially treated with contemporary chemotherapy. METHODS: The authors reviewed the clinical features, therapy, and outcome for 59 patients from the Mayo Clinic (Rochester, MN) and Children's Hospital and Regional Medical Center (Seattle, WA). They were diagnosed initially with OS between January 1990 and December 2000, received multiagent chemotherapy (most frequently cisplatin, doxorubicin, high-dose methotrexate, and ifosfamide), and developed disease recurrence after achieving an initial complete response (CR). RESULTS: The most common site of initial disease recurrence was the lung only (n = 36 patients), followed by distant bone (n =8 patients), combined lung and other sites (n =7 patients), and other sites (n =8 patients). The median time to first disease recurrence was 15 months (range, 2-92 months) from the initial diagnosis. Thirty patients with isolated pulmonary recurrence achieved a second CR, either with surgery alone (n =15 patients) or surgery and salvage chemotherapy (n =15 patients). For this group, the 4-year disease-free survival (DFS) and overall survival rates were 7% (95% confidence interval [95% CI], 0-16%) and 28% (95% CI, 11-45%), respectively. For all 59 patients with recurrent OS, the 4-year DFS and overall survival rates were 6% (95% CI, 0-12%) and 23% (95% CI, 10-36%), respectively. The only factors associated with improved DFS and overall survival rates were unilateral pulmonary recurrence, solitary pulmonary nodule at recurrence, more than 24 months between the initial diagnosis and first disease recurrence, and achievement of a second CR. CONCLUSIONS: The DFS and overall survival rates for recurrent OS after contemporary therapy remained poor even for patients with isolated pulmonary recurrence. Therefore, new treatment strategies are needed.     

Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy

PURPOSE: To evaluate prospectively the impact of combination chemotherapy in the combined modality treatment of isolated first locoregional recurrence (LRR) following mastectomy for breast cancer. METHODS AND MATERIALS: Between 1979 and 1989, 120 chemotherapy-naive women with isolated LRR as first failure after mastectomy were prospectively identified, uniformly staged, and systematically followed. Treatment consisted of excision if feasible, radical locoregional radiotherapy, and a hormonal maneuver (unless estrogen receptor negative). The initial chemotherapy cohort also received 8 cycles of doxorubicin and cyclophosphamide. This was compared to a subsequent control cohort. RESULTS: For all patients, the 10-year actuarial relapse-free survival +/- 95% confidence interval was 42.1+/-9.2%, and overall survival was 56.8+/-9.1%. No difference was seen in locoregional control between cohorts. At 5 years, distant recurrence-free survival for chemotherapy and control cohort respectively was 75.4+/-10.8% and 60.7+/-12.5% (p = 0.33) and overall survival was 81.9%+/-9.6 and 74.3%+/-11.2 (p = 0.24). Univariate analysis showed no prognostic importance for any imbalance between cohorts. Cox modeling confirmed that complete resection was strongly associated with fewer LRR (hazard ratio [HR] 0.32, p = 0.001) and also with better overall survival (HR 1.82, p = 0.019). Chemotherapy produced a substantial reduction in risk of death (HR 0.72 CI 0.421-1.235, p = 0.23). CONCLUSIONS: In this prospective but nonrandomized study of treatment for first LRR, the risk of death in the later control cohort was 1.39 times the risk in the chemotherapy cohort but failed to reach statistical significance. The results justify further study.     

Breast recurrence following conservative surgery and radiation: patterns of failure, prognosis, and pathologic findings from mastectomy specimens with implications for treatment

Between 1978 and 1986, 1030 women with clinical Stage I or II breast cancer underwent excisional biopsy, axillary dissection (948 patients), and definitive irradiation. Sixty-five patients developed a recurrence in the treated breast, 9 of which were associated with simultaneous (8) or antecedent (1) distant metastases. Detection was by mammography alone in 29%, physical exam alone in 50%, and both in 21%. The median interval to recurrence was 34 months. Overall, 65% of the recurrences were in the vicinity of the original tumor; however, as the interval to recurrence increased, the percentage of operable recurrences in a separate quadrant increased. For those recurring after 5 years, 54% were in a separate quadrant. Ninety-five percent of the recurrences unassociated with distant metastases were operable and pathology revealed non-invasive cancer only in 10%. Fifty-two patients underwent salvage mastectomy. Thirteen patients had no residual tumor following excisional biopsy at the time of mastectomy. None of the following factors were predictive for no residual tumor: initial age, method of detection, interval to recurrence, location of recurrence, or histology. Local-regional control following mastectomy was 95%. The 5-year actuarial overall and disease-free survivals for salvage mastectomy patients were 84% and 59%, respectively. The only significant prognostic factor for survival was the initial clinical tumor size, which was related to the extent of the recurrence. Based on the inability to identify factors which would predict for a localized recurrence pathologically, we recommend mastectomy as the preferred surgical treatment for an isolated breast recurrence. Adjuvant chemotherapy may be beneficial in patients with an unfavorable prognosis.     

Loco-regional recurrences after mastectomy in breast cancer: prognostic factors and implications for postoperative irradiation

Purpose: Potential risk factors including DNA flow cytometric-derived parameters predicting loco-regional recurrence (LRR) in early breast cancer were investigated.

Materials and methods: This study included 608 patients treated by modified radical mastectomy between 1982 and 1987. Recommendations regarding local treatment as well as adjuvant systemic therapy did not change during this period. Patients treated by adjuvant chemotherapy were randomized to receive additional medroxyprogesterone acetate (MPA) treatment. Only 59 (10%) patients received postoperative irradiation (XRT) to the chest wall and/or axillary lymph nodes; another 121 (20%) patients received XRT to the internal mammary nodes because of centromedially located tumours.

Results: Patients were followed for a median period of 7.5 years. The event-free survival at 10 years was 50%. The cumulative incidence rate of LRR at 10 years was 18% (n=93), either with (n=30) or without (n=63) concurrent distant metastases. The chest wall, regional lymph nodes or both were involved in 41 (44%), 38 (41%) and 12 (13%) patients, respectively. Multivariate analysis according to the Cox model revealed two factors associated with LRR, i.e. pT (P<0.05) and nodal status (P<0.05). In node-positive patients extracapsular tumour extension (ECE) and pT were independent risk factors. DNA ploidy and S-phase fraction did not yield additional information. Based on pT, nodal status and extracapsular extension of tumour growth a high risk (>10%) and low risk (<10%) group for LRR could be identified.

Conclusions: Results indicate that T-stage and nodal status, combined with ECE, may help to identify patients at risk for loco-regional recurrence, whereas DNA flow cytometry does not.     

Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy

PURPOSE: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. RESULTS: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis. CONCLUSION: LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.     

Local, regional, and systemic recurrence rates in patients undergoing skin-sparing mastectomy compared with conventional mastectomy

BACKGROUND:

Although the use of SSM is becoming more common, there are few data on long‐term, local‐regional, and distant recurrence rates after treatment. The purpose of this study was to examine the rates of local, regional, and systemic recurrence, and survival in breast cancer patients who underwent skin‐sparing mastectomy (SSM) or conventional mastectomy (CM) at our institution.

METHODS:

Patients with stage 0 to III unilateral breast cancer who underwent total mastectomy at our center from 2000 to 2005 were included in this study. Kaplan‐Meier curves were calculated, and the log‐rank test was used to evaluate the differences between overall and disease‐free survival rates in the 2 groups.

RESULTS:

Of 1810 patients, 799 (44.1%) underwent SSM and 1011 (55.9%) underwent CM. Patients who underwent CM were older (58.3 vs 49.3 years, P<.0001) and were more likely to have stage IIB or III disease (53.0% vs 31.8%, P<.0001). Significantly more patients in the CM group received neoadjuvant chemotherapy and adjuvant radiation therapy (P<.0001). At a median follow‐up of 53 months, 119 patients (6.6%) had local, regional, or systemic recurrences. The local, regional, and systemic recurrence rates did not differ significantly between the SSM and CM groups. After adjusting for clinical TNM stage and age, disease‐free survival rates between the SSM and CM groups did not differ significantly.

CONCLUSIONS:

SSM is an acceptable treatment option for patients who are candidates for immediate breast reconstruction. Local‐regional recurrence rates are similar to those of patients undergoing CM. Cancer 2011. © 2010 American Cancer Society.     

Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score

PURPOSE: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. METHODS: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size>2 cm, and multifocal residual disease. RESULTS: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p=0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p=0.009). CONCLUSIONS: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation.     

New prognostic factors associated with long-term survival in node-negative breast cancer patients

Background  This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Patients and Methods  Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). Results  Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. Conclusion  PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.