Locoregional radiotherapy in patients with breast cancer responding to neoadjuvant chemotherapy: a paradigm for treatment individualization.
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ABSTRACT:
SUBMITTER: White J
PROVIDER: S-EPMC5612477 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy.This was an institutional review board-approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservation or mastectomy), and adjuvant radiation therapy between 1997 and 2015. Medical records were reviewed for clinical stage, tumor grade and subtype, neoadjuvant chemotherapy regimen, type of surgery, pathologic stage, use of radiation therapy, date and location of recurrence, and date of death. Molecular subtypes were defined using immunohistochemistry and histologic grade. ypT0 and ypN0 were defined as no residual invasive disease in breast or nodes, respectively. LRR was defined as any failure within the breast, chest wall, or regional lymph nodes. Statistical analysis was performed; LRR and DFS rates over 30 months were determined from Kaplan-Meier plots.Ninety-four patients with TNBC were analyzed, of whom 72 received radiation therapy. This subgroup was isolated for further investigation. Median follow-up was 32.5 months in this group. The pathologic complete response (pCR) rate was 36%, and presence or absence of disease in breast and/or nodes was significantly predictive of LRR. In TNBC patients who received radiation therapy, 30-month LRR was 22% in 41 patients with ypT+ versus 0% in 31 patients with ypT0 (P = .003), 23% in 31 patients with ypN+ versus 5% in 41 patients with ypN0 (P = .016), and 20% in 46 patients with residual disease in breast or nodes versus 0% in 26 patients with pCR (P = .015). The difference in the rate of LRR between those who underwent lumpectomy versus mastectomy did not reach significance (8% vs 17%, respectively). Furthermore, patients with residual disease had a higher rate of DFS events (hazard ratio, 3.58; 95% confidence interval, 1.37-9.41; P = .006). The difference in DFS was not significantly associated with the type of surgery received.Patients with TNBC treated with neoadjuvant chemotherapy who have residual disease in the breast or lymph nodes at the time of surgery have significantly higher rates of locoregional failure and lower DFS compared with those with a pCR despite the use of adjuvant radiation therapy. Strategies to intensify therapy for patients with residual disease warrant further investigation.
| S-EPMC5514240 | biostudies-other
Project description:ObjectiveIn order to identify risk factors associated with locoregional recurrence (LRR) and assess the role of postmastectomy radiotherapy (PMRT) in early breast cancer (BC), managed with neoadjuvant chemotherapy (NAC) and mastectomy, a retrospective analysis of BC diagnosed with clinical stage T1-2N0-1 was conducted.Patients and methodsA total of 217 patients were included in this analysis. The median age was 50 years (24-72 years). The clinical stage distributions were cT1 in 15 cases, cT2 in 202, cN0 in 53, and cN1 in 161 cases. All patients were treated with NAC and mastectomy, and 128 patients received PMRT.ResultsWith a median follow-up time of 61 months, the 5-year cumulative LRR rate was 12%. Multivariate analysis demonstrated that pathological N stage, lymph-vascular invasion, and histological grade were independent prognostic factors associated with LRR. A nomogram model based on these factors was established, based on which the patients were deeply stratified into low- and high-risk group. In the low-risk group, radiotherapy did not decrease LRR (3.3% in PMRT group, 1.7% in no PMRT group, P=0.192). While in the high-risk group, PMRT significantly decreased LRR (21.8% in PMRT group, 42.2% in no PMRT group, P=0.031).ConclusionLymph-vascular invasion, histological grade, as well as pathological N stage were important prognostic factors associated with LRR in BC patients staged in cT1-2N0-1, who were managed with NAC and mastectomy. In our cohort, not only clinical and pathological stage information but also other risk factors were taken into consideration when adjuvant PMRT was recommended. In the high-risk subgroup, PMRT significantly improved the prognosis.
| S-EPMC6174313 | biostudies-literature
Project description:When surgery is the first line of breast cancer treatment, numerous randomized clinical trials and meta-analyses have demonstrated that postmastectomy radiation therapy (PMRT) improves locoregional control and survival for many women with axillary lymph node-positive disease. In contrast, there are no randomized data regarding the use of PMRT in women who receive neoadjuvant chemotherapy (NAC) first followed by mastectomy. This has led to controversy regarding which patient with breast cancer will benefit from PMRT after NAC, particularly in women with clinically node-positive axillary disease that responds well and is down staged to pathologically negative disease at surgery (ypN0). We review the current evidence on this topic, which forms the underlying basis for the ongoing phase III clinical trial-National Surgical Adjuvant Breast and Bowel Project (NSABP) B51/RTOG 1304-that is examining the role of regional nodal irradiation in patients with clinical N1 disease that responds to NAC and becomes ypN0 at surgery.
| S-EPMC4718394 | biostudies-literature
Project description:Radiotherapy is today used in about 50% of all cancer patients, often in multidisciplinary approaches. With major advance in radiotherapy techniques, increasing knowledge on tumor genetics and biology and the continuous introduction of specifically targeted drugs into combined radio-oncological treatment schedules, individualization of radiotherapy is of high priority to further improve treatment outcomes, i.e. to increase long-term tumor cure and/or to reduce chronic treatment toxicity. This review gives an overview on the importance of predictive biomarkers for the field of radiation oncology. The current status of knowledge on potential biomarkers of tumor hypoxia, tumor cell metabolism, DNA repair, cancer stem cells and biomarkers for combining radiotherapy with inhibition of the epidermal growth factor receptor using monoclonal antibodies is described.
| S-EPMC5528361 | biostudies-literature
Project description:Triple-negative breast cancer is a high-risk breast cancer with poor survival rate. To date, there is a lack of targeted therapy for this type of cancer. One unique phenomenon is that inflammatory breast cancer is frequently triple negative. However, it is still ambiguous how inflammation influences triple-negative breast cancer growth and responding to chemotherapy. Herein, we investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple-negative breast cancer patients' tumors, and examined its correlation with patients' responses to platinum-based neoadjuvant chemotherapy. Our studies showed that triple-negative breast cancer patients with attenuated iNOS levels in tumor cells after treatment showed better responses to platinum-based neoadjuvant chemotherapy than other triple-negative breast cancer patients. Our further in vitro studies confirmed that induction of proper levels of NO increased the resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest that aberrant high level of iNOS/NO are associated with less effectiveness of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer. Therefore, we propose to monitor iNOS levels as a new predictor for triple-negative breast cancer patient's response to platinum-based neoadjuvant chemotherapy. Moreover, iNOS/NO is considered as a potential target for combination therapy with platinum drugs for triple-negative breast cancer.
| S-EPMC4510059 | biostudies-literature
Project description:We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO2) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO2 in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate "normalization" of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome.
| S-EPMC5330555 | biostudies-literature
Project description:This study aimed to determine whether post-mastectomy radiotherapy (PMRT) is beneficial for the prognosis of patients who achieved pathologic complete response (pCR), or who had minimal residual disease, after undergoing neoadjuvant chemotherapy (NAC). Patients who underwent a total mastectomy between 2006 and 2018, after NAC, were included. Patients who did not receive PMRT were matched using 1:3 propensity score matching (PSM). Kaplan-Meier survival curves were used to compare locoregional recurrence-free survival (LRRFS) and overall survival (OS). A total of 368 patients were included after 1:3 PSM. PMRT improved the LRRFS (p = 0.016) and OS (p = 0.017) rates of patients who underwent NAC. However, PMRT did not affect the prognosis of patients with pCR (LRRFS: p = 0.999; OS: p = 0.453). In addition, PMRT had a limited effect on LRRFS and OS in patients who responded well to NAC, with a neoadjuvant response index (NRI) value of 0.7-1.0 (LRRFS: p = 0.568; OS: p = 0.875). PMRT improved the OS of patients with a large residual tumor burden, such as nodal metastases or pathologic stage II/III. The benefits of PMRT vary depending on the patients' response to NAC, although PMRT is useful for treating patients who underwent NAC. PMRT can be omitted, not only in patients with pCR, but also in good responders with an NRI value of 0.7-1.0.
| S-EPMC8699474 | biostudies-literature
Project description:The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients treated with neoadjuvant chemotherapy (NAC), mastectomy, and postmastectomy radiotherapy (PMRT) is not clearly defined.233 patients with stages 2 and 3 breast cancer who received NAC, mastectomy, and PMRT between 2000 and 2009 were included: 53 % (n = 123) had HR+ (ER or PR+/HER2-), 23 % (n = 53) had HER2+ (HER2+/HR+ or HR-), and 24 % (n = 57) had triple-negative (TN) disease (HR-/HER2-). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR.The median follow-up period was 62 months. A pathologic complete response (pCR) was seen in 14 % of the patients. The 5-year LRR rate was 8 % for the entire cohort. The LRR rate was 0 % for the patients with a pCR versus 9 % for the patients without a pCR (p = 0.05). TN disease [Hazard ratio (HR) 4.4; p = 0.003] and pathologic node positivity (HR 9.8; p = 0.03) were associated with LRR. Patients with TN disease had a higher LRR rate than patients with HER2+ or HR+ disease (20 vs. 6 and 4 %; p = 0.005). Among patients without a pCR, TN subtype was associated with increased LRR risk (26 versus 7 % HER+ and 4 % HR+; p < 0.001).Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. Whereas no LRR was observed among TN patients with a pCR, TN patients with residual disease had a significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies.
| S-EPMC5005073 | biostudies-other
Project description:Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here, we undertook a retrospective comprehensive meta-analysis of 13,322 breast cancer patients from 43 independent cohorts to assess prognostic and predictive roles of Txnrd1. We observed that Txnrd1 has a positive correlation with tumor grade and size and it is over-expressed in higher-grade and larger tumors. Further, hormone receptor-negative and HER2-positive tumors exhibit elevated Txnrd1 gene expression. Patients with elevated Txnrd1 expression exhibit significant hazards for shorter disease-specific and overall survival. While Txnrd1 has a positive correlation with tumor recurrence and metastasis, it has a negative correlation with time to recurrence and metastasis. Txnrd1High patients exhibit 2.5 years early recurrence and 1.3 years early metastasis as compared to Txnrd1Low cohort. Interestingly, patients with high Txnrd1 gene expression exhibit a pathologic complete response (pCR) to neoadjuvant chemotherapy, but they experience early recurrence after radiotherapy. Txnrd1High MDA-MB-231 cells exhibit significant ROS generation and reduced viability after doxorubicin treatment compared to Txnrd1Low MCF7 cells. Corroborating with findings from meta-analysis, Txnrd1 depletion leads to decreased survival, enhanced sensitivity to radiation induced killing, poor scratch-wound healing, and reduced invasion potential in MDA-MB-231 cells. Thus, Txnrd1 appears to be a potential predictor of recurrence, metastasis and therapy response in breast cancer patients.
| S-EPMC10958228 | biostudies-literature
Project description:AimTo investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT).Methods and materialsAbout 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A-like, Luminal B-like, HER2-positive, and triple-negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray.ResultsThe median follow-up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2-positive, and TNBC patients, the 5-year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2-positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2-positive subtype (HR = 4.43, P < .05), TNBC (HR = 4.70, P < .05), and pN3 (HR = 5.83, P < .05). In the multivariate model, HER2-positive subtype (HR = 5.034, P < .05), TNBC (HR = 5.188, P < .05), and pN3 (HR = 9.607, P < .01) were independent predictors of LRR. LRR without trastuzumab was similar to that of TNBC (without vs TNBC, 17.88% vs 10.28%, P > .05) in HER2-positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P > .05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P < .1).ConclusionsBiological subtype was a prognostic factor of LRR in the PMRT setting among Chinese breast cancer patients.
| S-EPMC7131860 | biostudies-literature