Significant Risk Factor For Local Recurrence Research Articles

Molecular subtype and risk of local recurrence after nipple‑sparing mastectomy for breast cancer.

The present study aimed to investigate whether local recurrence (LR) after nipple-sparing mastectomy (NSM) and reconstruction was associated with i) Ki67 values and molecular subtypes of the initial lesions, and ii) the size of the initial tumor and the size of the implant. A total of 156 patients with breast cancer with a mean age of 51.58 years (age range, 26-75 years) who underwent NSM with primary implant breast reconstruction were analyzed. After surgery, the mean follow-up time was 59.26 months (range, 17-85 months). Molecular subtypes, Ki67 values, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were recorded for each patient. Additionally, information regarding the size of the implant and the initial tumor size were collected. The information was used to assess LR. For univariate analyses of risk factors, χ2 test, Fisher's exact test, Mann-Whitney U test and Student's t-test for independent samples were used. For multivariate analyses, a Cox proportional-hazards model was used. NSM was the primary treatment for breast cancer in 34/156 patients (21.8%), while 122/156 (78.2%) of patients received neoadjuvant chemotherapy followed by surgery. Luminal B was the most frequent molecular subtype, detected in 82/156 patients (52.6%), whereas the luminal A subtype was detected in 37 patients (23.7%) and the HER2-enriched subtype was detected in 17/156 patients (10.9%). Ki67 expression was low in 13/156 patients (8.3%), while medium expression was detected in 78/156 patients (50.0%) and high expression was present in 58/156 patients (37.2%). LR was noted in 17/156 patients (10.9%). As determined by univariate analysis, lower ER (P=0.010) and PR (P=0.008) expression were indicated to be significant risk factors for LR. In conclusion, in the present patient cohort, low ER and PR expression were risk factors for LR of breast cancer, whereas Ki67 status and molecular subtype were not statistically significant risk factors for LR. Additionally, the size of the initial tumor and the size of the implant were not risk factors for LR. These findings are consistent with the current literature, and should be utilized when discussing treatment options and potential clinical outcomes with patients prior to surgical management.

Local Recurrence of Rectal Cancer After Transanal Total Mesorectal Excision and Risk Factors: A Nationwide Multicenter Cohort Study in Japan.

To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50-6.75) and 6.82% (95% confidence interval: 5.08-8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR. Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors. The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68-2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05-1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs. The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.

Margin Proximity Correlates with Local Recurrence After Mastectomy for Patients Not Receiving Adjuvant Radiotherapy.

Although considerable evidence exists regarding margin status and reexcision for patients undergoing breast conservation therapy, few data address the impact of a close margin for patients undergoing mastectomy without postmastectomy radiotherapy. This retrospective review identified 1147 patients who underwent 1206 mastectomies with negative final margins for breast cancer from 2006 to 2010. Margin distance was analyzed as a continuous variable and dichotomized variable ((≤2 vs >2mm). Patients undergoing adjuvant radiation therapy were excluded from the study. Uni- and multivariable analyses were used to assess the association of reexcision, proximity of the final margin, adjuvant therapy, and other clinical and pathologic factors with local recurrence (LR). In 158 mastectomies (13.1%), a reexcision was performed for a close (n=90) or positive (n=68) margin. All but one were identified intraoperatively using frozen section analysis. The reexcision rates for skin- and nipple-sparing mastectomy (SSM/NSM) were higher than for simple mastectomy (SM) (19.8 vs 9.3%; p<0.001). The overall 5-year risk for an LR was 3.8%. The risk was 3.1% for a margin greater than 2mm and 11.2% for a margin of 2mm or smaller. In the multivariable model, proximity of the final margin measured as a continuous variable was found to be a significant risk factor for LR (p=0.009), whereas adjuvant endocrine therapy was found to be protective (p=0.03). Intraoperative reexcision was not significant in the multivariable model (p=0.23). For patients undergoing mastectomy for breast cancer, a wider final margin correlated with a reduced risk for LR. The rates for LR were similar between SSM/NSM and SM despite higher rates of intraoperative reexcision for SSM/NSM.

Abstract PD04-03: Is breast conservation therapy an option for young women with operable breast cancer? Local recurrence rates in young women following surgery: a single centre experience.

Abstract Background: Breast cancer (BC) is less common in young women (defined here as ≤ 40 years age), but is associated with more aggressive biological features, higher risk of local recurrence (LR) and poorer overall survival. This study examines and compares the incidence of LR following breast conservation therapy (BCT) versus mastectomy in women with operable BC treated at our centre. Methods: The POWCC breast cancer database was retrospectively reviewed for the period January 1995 to December 2008. 2250 eligible women with BC undergoing primary breast surgery were identified. LR rate was compared between young women and older women (age &amp;gt; 40 years), and according to type of surgery. Data were analysed using a competing risk Cox model to account for distant recurrence and death as competing events for local recurrence. Results: Median follow-up was 70 months. Of 2250 women, 246 (11%) were young women, and the mastectomy rate was 49.2%. In older women (89%), mastectomy rate was 41.7%. LR occurred in 17 (6.9%) and 57 (2.8%) in young and older women respectively (p = 0.001). Amongst the young women, 12 (9.6%) and 5 (4.1%) patients recurred locally in BCT and mastectomy respectively (p = 0.09). Amongst the older women, 43 (3.7%) and 14 (1.7%) patients recurred locally in BCT and mastectomy respectively (p = 0.008). In univariate Cox analysis, significant risk factors for LR were BCT (p = 0.003), positive surgical margins (p = 0.03), age ≤ 40 years (p = 0.001), premenopausal status (p = 0.003) and no adjuvant systemic therapy (0.02). Age remains a significant predictor of LR in multivariate Cox analysis (Table). There was no significant interaction between age and type of surgery on LR (p = 0.72). Discussion: Our results demonstrate that young women who undergo BCT have the highest risk of early LR. Adjuvant systemic therapy is protective of early LR. This study is hypothesis-generating and a definitive prospective clinical trial is required to better determine the optimal type of breast surgery in young women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD04-03.

The Association between Surgical Closure Type and Acute Infection, Local Recurrence, and Disease Surveillance in Patients Undergoing Breast Conserving Therapy For Early Stage Breast Cancer

Purpose/Objective: In patients undergoing breast-conserving therapy (BCT), surgical closure technique has been largely influenced by expected cosmetic outcome. However, the common practice of promoting postoperative fluid collection raises concerns about potential bacterial colonization, tumor cell migration, and impaired post-BCT surveillance. This study investigates the effect of full-thickness versus superficial closure of the breast parenchyma on the likelihood of subsequent infection and local recurrence. Materials/Methods: From 1985 through 2004, 577 women with 599 stage T0-2N0-1 breast cancers underwent BCT at our institution. Medical records were reviewed to determine surgical closure technique, incidence of post-operative infection, local recurrence (LR), and ipsilateral breast tumor recurrence (IBTR). Three surgeons performed the majority of operations. Re-excision of the tumor bed was performed in patients with close or positive margins when feasible. In all patients, radiation treatment was planned using computed tomography (CT) scans. The tumor bed target included postoperative fluid collections, tumor bed clips, and postoperative tissue changes. Acute infection was diagnosed on a clinical basis within three months of surgery. Results: Median observed follow-up was 6.4 years from the completion of radiotherapy. Surgical closure technique was determined in 514 patients. Acute infections occurred in 27/229 (11.8%) breasts known to have superficial closure compared with 15/285 (5.3%) with full-thickness closure (p=0.0091). In stage T1–2 patients, the overall 10-year actuarial rates of IBTR and LR were 5% and 3%. In this group of patients with invasive cancer, there was no difference between superficial and full-thickness closure in the rate of either IBTR 5.6% (11/195) vs. 3.5% (8/230) or LR 3.6% (7/195) vs. 1.7% (4/230). In Stage T0-T2 patients, local recurrences following superficial closure were less likely to be initially detected on mammography 29% (2/7) vs. 100% (10/10) p=0.0034 compared to local recurrences following full-thickness closure. In addition, when locally recurrent tumors were identified in mastectomy specimens of stage T0-T2 patients, 80% (4/5) of recurrent tumors after superficial closures were >1 cm compared with no (0/9) (p=0.0050) recurrent tumors after full-thickness closures. A Cox multivariate analysis was performed examining factors potentially associated with IBTR and LR including: surgical closure type, age, infection, obesity, tumor bed radiation dose, hormonal therapy, and surgical margin status. Only close (<2 mm) or positive margins were significant risk factors for both IBTR and LR (p = 0.0147 and 0.0177). Acute infection was also a significant risk factor for LR alone (p = 0.0034). Conclusions: In the University of Florida BCT experience, women with superficial closures after partial mastectomy had an increased risk of infection, which itself was associated with a higher risk of local recurrence. Additionally, local recurrences after superficial closure may be more difficult to detect on surveillance imaging, permitting the development of larger recurrent tumors.

Risk factors for local recurrence after breast-conserving therapy for invasive carcinomas: a case-control study of histological factors and alterations in oncogene expression

Purpose: Many studies have focused on histological risk factors for local recurrence (LR) after breast-conserving therapy (BCT). In addition to histological factors, we studied alterations in the expression of various proteins in relation to LR using a case-control approach. Methods and Materials: Ninety-nine LR occurred in a patient cohort of 1,481 tumors treated with BCT. These patients were randomly matched, each with two controls. Matching was performed for age group (≤ 50 and > 50 years), pN stage, and follow-up time. Histology slides were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, CD31, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c- erbB2/ neu, and p53. Statistical analyses were performed using conditional logistic regression. Results: Sixty-six cases and 139 controls with invasive carcinoma remained for analysis. The following variables were significant risk factors for LR: young age ( p = 0.006), high nuclear grade ( p = 0.04), high mitotic count ( p = 0.03), extensive DCIS around the tumor ( p = 0.02) but not within the tumor, poorly differentiated type of DCIS ( p = 0.03), > 20% ki-67 positive cells ( p = 0.006), and PR negativity ( p = 0.03). When the analysis was performed for patients ≤ and > 50 years, these risk factors were found in the older patients, but not in the younger patients. Conclusion: High mitotic count and Ki-67 positivity are risk factors for LR. EDCIS surrounding the invasive tumor is a risk factor for LR, especially when of poorly differentiated type. Age is an important risk factor for LR independent of other risk factors, including alterations in oncogene expression.