Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 2005
Purpose: To identify the clinical and pathologic factors predictive of locoregional recurrence (LRR) after neoadjuvant chemotherapy, mastectomy, and radiotherapy. Methods and Materials: We retrospectively reviewed the hospital records of 542 patients treated on six consecutive institutional prospective trials using neoadjuvant chemotherapy and postmastectomy radiotherapy. The clinical stage (American Joint Committee on Cancer, 1988) was Stage II in 17%, Stage IIIA in 30%, Stage IIIB in 43%, and Stage IV (ipsilateral supraclavicular disease) in 10%. All LRRs were considered events, irrespective of the timing to distant metastases. Results: The median follow-up was 70 months. The 5-year and 10-year actuarial LRR rate was 9% and 11%, respectively. The clinical factors associated with LRR included combined clinical stage, clinical T stage, ipsilateral supraclavicular nodal disease, chemotherapy response, physical examination size after chemotherapy, and no tamoxifen use (p < 0.04 for all factors). The pathologic predictors of LRR included the number of positive nodes, dissection of <10 nodes, multifocal/multicentric disease, lymphovascular space invasion, extracapsular extension, skin/nipple involvement, and estrogen receptor-negative disease (p < 0.05 for all factors). Multivariate Cox regression analysis revealed that five factors independently predicted for LRR: skin/nipple involvement, supraclavicular nodal disease, no tamoxifen use, extracapsular extension, and estrogen receptor-negative disease (hazard ratio, 2.1-2.8; p < 0.02 for all factors). The 10-year LRR rate was only 4% for patients with one or none of these five independent factors, 8% for those with two factors, and 28% for those with three or more factors (p < 0.0001). Conclusion: Although the long-term rate of LRR after neoadjuvant chemotherapy, mastectomy, and radiotherapy is low, we identified a number of factors that correlated independently with greater rates of LRR. Patients with three or more of these factors may benefit from research protocols investigating alternative treatment strategies.
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: To compare the pathologic factors associated with postmastectomy locoregional recurrence (LRR) in breast cancer patients not receiving radiation who were treated with neoadjuvant chemotherapy (NEO) vs. adjuvant chemotherapy (ADJ). Methods and Materials: We retrospectively analyzed the rates of LRR of subsets of women treated in prospective trials who underwent mastectomy and received chemotherapy but not radiation. These trials were designed to answer chemotherapy questions. There were 150 patients in the NEO group and 1031 patients in the ADJ group. In the NEO group, 55% had clinical Stage IIIA or higher vs. 9% in the ADJ group (p <0.001, chi-square test). Results: Despite the more advanced clinical stage in the NEO group, the pathologic size of the primary tumor and the number of positive lymph nodes (؉LNs) were significantly less in the NEO group than in the ADJ group (p <0.001 for both comparisons). However, the 5-year actuarial LRR rate was 27% for the NEO group vs. 15% for the ADJ group (p ؍ 0.001, log-rank). The 5-year risk for LRR was higher in the NEO patients for all pathologic tumor sizes: 0 -2 cm (18% vs. 8%, p ؍ 0.011), 2.1-5 cm (36% vs. 15%, p <0.001), and >5 cm (46% vs. 28%, p ؍ 0.028). The risk of LRR by the number of ؉LNs was similar in the NEO and ADJ groups, except for the subset of patients with >4 ؉LNs (53% vs. 23%, p <0.001). The rates of LRR in the patients with primary tumors measuring <2.0 cm and 1-3 ؉LNs were similar in both groups. However, for the patients with a pathologic tumor size of 2.1-5.0 cm and 1-3 ؉LNs, the LRR was higher in the NEO group than in the ADJ group (30% vs. 15%, p ؍ 0.016). Most failures in this NEO subgroup had clinical Stage III disease. In a subset of NEO and ADJ patients matched for clinical stage, no significant differences were found in the rates of LRR according to primary tumor size and number of ؉LNs when these variables were analyzed independently. Again, however, differences were found in the subgroup of patients with tumors pathologically measuring 2.1-5.0 cm with 1-3 ؉LNs (32% NEO vs. 8% ADJ, p ؍ 0.030). Conclusion: The rates of postmastectomy LRR for any pathologic tumor size are higher for patients treated with initial chemotherapy than for patients treated with initial surgery. Radiotherapy should be offered to all patients with >4 ؉LNs, tumor size >5 cm, or clinical Stage IIIA or greater disease, regardless of whether they receive neoadjuvant or postoperative chemotherapy. The information assessing LRR rates in patients with clinical Stage II disease who receive neoadjuvant chemotherapy, particularly if 1-3 lymph nodes remain pathologically involved, is insufficient to determine whether these patients should receive radiotherapy.
European Journal of Cancer, 2020
This pooled analysis aimed to evaluate locoregional recurrence (LRR) rates of breast cancer (BC) after neoadjuvant chemotherapy (NACT) and to identify independent LRR predictors. Methods: 10,075 women with primary BC from nine neoadjuvant trials were included. The primary outcome was the cumulative incidence rate of LRR as the first event after NACT. Distant recurrence, secondary malignancy or death were defined as competing events. For identifying LRR predictors, surgery type, pathological complete response (pCR), BC subtypes and other potential risk factors were evaluated. Results: Median followup was 67 months (range 0e215), overall LRR rate was 9.5%, 4.1% in pCR versus 9.5% in non-pCR patients. Younger age, clinically positive lymph nodes, G3 tumours, non-pCR and TNBC but not surgery type were independent LRR predictors in multivariate analysis. Among BC subtypes, 5-year cumulative LRR rates were associated with higher risk in non-pCR versus pCR patients, which was significant for HRþ/HER2-(5.9% vs 3.9%; HR Z 2.32 [95%CI 1.22e4.43]; p Z 0.011); HR-/HER2þ (14.8% vs 3.1%; HR Z 4.26 [94%CI 2.35e7.71]; p < 0.001) and TNBC (18.5% vs 4.2%; HR Z 4.10 [95%CI 2.88e5.82]; p < 0.001) but not for HRþ/HER2þ (8.1% vs 4.8%; HR Z 1.56 [95%CI 0.85 e2.85]; p Z 0.150). Within non-pCR subgroup, LRR risk was higher for HR-/HER2þ and TNBC vs HRþ/HER2-(HR Z 2.05 [95%CI 1.54e2.73]; p < 0.001 and HR Z 2.77 [95%CI 2.27e3.39]; p < 0.001, respectively). Conclusions: This pooled analysis demonstrated that young age, node-positive and G3 tumours, as well as TNBC, and non-pCR significantly increased the risk of LRR after NACT. Hence, there is a clear need to investigate better multimodality therapies in the postneoadjuvant setting for high-risk patients.
Breast Cancer Research and Treatment, 2010
Recent pre-clinical models suggest that radiation can promote tumor aggressiveness. We hypothesized that if this were occurring clinically, locoregional recurrences (LRRs) after postmastectomy radiation therapy (PMRT) would lead to lower survival than LRR after mastectomy alone. This study used two independent data-sets to compare survival after LRR in women treated with versus without PMRT. Data from 229 LRR cases among 1,500 patients enrolled on prospective trials at the MD Anderson Cancer Center (MDA), and 66 LRR cases among 318 patients enrolled in the British Columbia Cancer Agency (BCCA) PMRT randomized trial were analyzed. In the MDA non-randomized dataset, 189/1031 had LRR after mastectomy alone and 40/469 had LRR after PMRT. In the randomized BC trial dataset, 52/158 had LRR after mastectomy alone and 14/160 had LRR after PMRT. In both datasets, survival was calculated from the time of LRR to death. Analysis of MDA data shows that in all LRR cases regardless of distant metastasis (DM), 5/10-year OS were 50/34% without PMRT and 27/19% after PMRT (P = 0.006). However, PMRT-treated patients had increased risk factors for DM (advanced T and N stages) and more PMRT-treated patients developed DM prior to LRR (63 vs. 34%, P = 0.005). Analyzing only patients will an isolated LRR (without previous or simultaneous DM), there was no OS difference between groups (P = 0.33). Analysis of BCCA data shows that distributions of T and N stages were similar in patients with LRR after mastectomy alone versus after PMRT. DM free survival after any LRR and after isolated LRR were similar in mastectomy alone versus PMRT-treated patients (P = 0.75, P = 0.26, respectively). Overall survival after any LRR and after isolated LRR were also similar in the two groups (P = 0.93, P = 0.28, respectively). Patients who develop LRR after mastectomy alone have high rates of DM and poor OS but these rates are not affected by the use of PMRT at the time of primary treatment. These data do not support the hypothesis that irradiation promotes biologically aggressive local recurrences. Woodward et al.
International Journal of Radiation Oncology*Biology*Physics, 2006
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). Conclusion: 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.
The Cambridge post-mastectomy radiotherapy (C-PMRT) index: A practical tool for patient selection
Radiotherapy and Oncology, 2014
Background and purpose: Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and has been associated with survival benefit. It is recommended for patients with T3/T4 tumours and/or P4 positive lymph nodes (LN). The role of PMRT in 1-3 positive LN and LN negative patients is contentious. The C-PMRT index has been designed for selecting PMRT patients, using independent prognostic factors for LRR. This study reports a 10 year experience using this index. Materials and methods: The C-PMRT index was constructed using the following prognostic factors (a) number of positive LN/lymphovascular invasion, (b) tumour size (c) margin status and (d) tumour grade. Patients were categorised as high (H) risk, intermediate (I) risk and low (L) risk. PMRT was recommended for H and I risk patients. The LRR, distant metastasis and overall survival (OS) rates were measured from the day of mastectomy. Results: From 1999 to 2009, 898 invasive breast cancers in 883 patients were treated by mastectomy (H: 323, I: 231 and L: 344). At a median follow up of 5.2 years, 4.7% (42/898) developed LRR. The 5-year actuarial LRR rates were 6%, 2% and 2% for the H, I and L risk groups, respectively. 1.6% (14/898) developed isolated LRR (H risk n = 4, I risk group n = 0 and L risk n = 10). The 5-year actuarial overall survival rates were 67%, 77% and 90% for H, I and L risk groups, respectively. Conclusion: Based on published literature, one would have expected a higher LRR rate in the I risk group without adjuvant RT. We hypothesise that the I risk group LRR rates have been reduced to that of the L risk group by the addition of RT. Apart from LN status and tumour size, other prognostic factors should also be considered in selecting patients for PMRT. This pragmatic tool requires further validation.