Impacts of Tumor Stage at Diagnosis and Adjuvant Therapy on Long-Term Survival Outcomes in Patients With Triple-Negative Breast Cancer Achieving Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.

Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters.

Complete pathological response (pCR) is achieved in 10−20% of rectal cancers when treated with short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (scRT/CRT + CTX). pCR is associated with better outcomes and a "watch-and-wait" strategy (W&W). The aim of this study was to identify baseline clinical or imaging factors predicting pCR. All patients with preoperative treatment and delays to surgery in Uppsala-Dalarna (n = 359) and Stockholm (n = 635) were included. Comparison of pCR versus non-pCR was performed with binary logistic regression models. Receiver operating characteristics (ROC) models for predicting pCR were built using factors with p < 0.10 in multivariate analyses. A pCR was achieved in 12% of the 994 patients (scRT 8% [33/435], CRT 13% [48/358], scRT/CRT + CTX 21% [43/201]). In univariate and multivariate analyses, choice of CRT (OR 2.62; 95%CI 1.34−5.14, scRT reference) or scRT/CRT + CTX (4.70; 2.23−9.93), cT1−2 (3.37; 1.30−8.78; cT4 reference), tumour length ≤ 3.5 cm (2.27; 1.24−4.18), and CEA ≤ 5 µg/L (1.73; 1.04−2.90) demonstrated significant associations with achievement of pCR. Age < 70 years, time from radiotherapy to surgery > 11 weeks, leucocytes ≤ 109/L, and thrombocytes ≤ 4009/L were significant only in univariate analyses. The associations were not fundamentally different between treatments. A model including T-stage, tumour length, CEA, and leucocytes (with scores of 0, 0.5, or 1 for each factor, maximum 4 points) showed an area under the curve (AUC) of 0.66 (95%CI 0.60−0.71) for all patients, and 0.65−0.73 for the three treatments separately. The choice of neoadjuvant treatment in combination with low CEA, short tumour length, low cT-stage, and normal leucocytes provide support in predicting pCR and, thus, could offer guidance for selecting patients for organ preservation.

A Proposal to Redefine Pathologic Complete Remission as Endpoint following Neoadjuvant Chemotherapy in Early Breast Cancer.

Many analyses of the efficacy of neoadjuvant treatment (NAT) for early breast cancer including a meta-analysis derived from 10 randomized trials came to the conclusion that patients who would achieve pathologic complete response (pCR) following NAT would experience significant improvement in disease-free and overall survival (OS). Thus, pCR was proposed as a surrogate endpoint for OS, with pCR representing a robust prognostic marker for survival at an individual level. In the current analysis, we argue that OS following NAT-induced pCR might have reflected the initial prognosis of patients mainly defined - among other factors - by the initial pathological lymph node status while being largely independent on the type of administrated treatment, thus pleading against the pCR surrogacy hypothesis. We therefore propose to redefine pCR as a surrogate endpoint of NAT trials by the involvement of additional biologic parameters.

A Rare Case of Triple Positive Metachronous Breast Cancer.

Metachronous contralateral breast cancer (MCBC) is defined as contralateral breast cancer (BC) diagnosed more than 1 year after previous BC diagnosis. More BC survivors are at risk of MCBC given improved life expectancy with the availability of advanced cancer care. Estrogen receptor/progesterone receptor negative and HER-2-positive status of first BC are independent risk factors for the development of MCBC. We present a rare case of triple positive (estrogen receptor, progesterone receptor, HER-2 positive) MCBC patient who eventually developed brain metastasis within 15 months despite a near complete pathologic response of primary tumor. This case highlights that even in this era of antiestrogen and anti-HER-2 therapies, triple positive MCBC can have an aggressive clinical course, especially with brain metastasis as the first sign of metastasis.

Magnetic Resonance Imaging (MRI) Assessment of Residual Breast Cancer After Neoadjuvant Chemotherapy: Relevance to Tumor Subtypes and MRI Interpretation Threshold.

PURPOSE: To investigate the diagnostic performance of magnetic resonance imaging (MRI) for predicting pathologic complete response after neoadjuvant chemotherapy (NAC) depending on subtypes of breast cancer using different interpretation thresholds of MRI negativity. PATIENTS AND METHODS: A total of 353 women with breast cancer who had undergone NAC were included. Pathologic examination after complete surgical excision was the reference standard. Tumors were divided into 4 subtypes on the basis of expression of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). Tumor enhancement was assessed on early and late phases of MRI. MRI negativity was divided into radiologic complete response (rCR, complete absence of enhancement on both early and late phases) and near-rCR (no discernible early enhancement but observed late enhancement). RESULTS: Ninety (25.5%) of 353 patients experienced pathologic complete response. When analyzing the data of all patients, sensitivity of MRI was higher for rCR versus near-rCR (97.72% vs. 90.49%, P < .0001), whereas specificity was lower for rCR versus near-rCR (44.44% vs. 72.22%, P < .0001). Accuracy was equivalent (84.14% vs. 85.84%). In HR-HER2+ tumors, 100% sensitivity and negative predictive value were achieved by assessing early enhancement only. In HR+HER2- tumors, sensitivity of MRI was higher for rCR versus near-rCR (96.12% vs. 86.82%, P = .0005). CONCLUSION: Diagnostic performance of MRI after NAC differs in accordance with the subtypes and threshold of MRI negativity. MRI assessment with consideration of tumor subtypes is required, along with standardization of MRI interpretation criteria in the NAC setting.

Tumor compactness improves the preoperative volumetry-based prediction of the pathological complete response of rectal cancer after preoperative concurrent chemoradiotherapy.

In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV (P = 0.0057) and CATV (P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness (P = 0.001), RTV (P = 0.042), and preoperative clinical nodal status (P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion (P = 0.008) and pathological nodal status (P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.

Attaining pathological complete regression for breast conservation - A pilot experience in a developing country.

CONTEXT: Local recurrence is a formidable risk consideration in employing breast conservation for breast cancer. However pathological complete regression (PCR) from chemotherapy has been associated with improved rates of recurrence. Lower PCR rates have been reported from earlier studies and our approach seeks to obtain higher PCR rates utilizing a two pronged approach of surgery and chemotherapy. OBJECTIVE: To determine success rates in attaining pathologically complete regression for breast conservation in non-metastatic breast cancer cases in a developing country and their clinical outcome. PATIENTS AND METHODS: Patients diagnosed with early stage breast cancers had sequential anthracycline/taxane based neoadjuvant/adjuvant chemotherapy administered at three weekly intervals. Following an initial excision, re-excisions were done following three courses of doxorubicin based chemotherapy. Subsequent re-excisions in cases with failed complete pathological regression were repeated following additional three doxorubicin based chemotherapy cycles or at sequel third taxane based cycle. Endpoint was pathologically complete regression as determined on permanent sections. RESULTS: Patients ages ranged between 27 and 67 years, mean age 43years, SD 10.34 years, N = 20 Initial breast tumour sizes ranged between 0.5 and 9 cm, mean 4.05 cm, SD 2.38. There were three T4, four T3 tumours, seven T2 and six T1 tumours. Clinical axillary lymphadenopathy with pathological involvement was present in 11 cases. Histological diagnosis showed 13 cases of invasive ductal carcinoma (65.0%), 2 cases of ductal carcinoma insitu (10.0%), 1 papillary carcinoma (5.0%), 3 cases of invasive lobular carcinoma (15.0%) and non-specific type 1 (5.0%). Immunohistochemistry assessment available in 15 cases was positive for estrogen and progesterone receptors in 10 cases. Two cases (10.0%) exhibited 20% positivity for human epidermal growth factor receptor. Pathological complete regression (PCR) defined as no invasive or insitu tumour residuals in the excised tumour bed, was achieved in the 18 cases assessed. (100%) This was consistent with clinical complete response obtained. It was not determined in 2 cases though clinical complete response was obtained. PCR was determined in ten cases (50.0%) at the first reexcision, second reexcision in 4 cases (20.0%) and third reexcision in 4 cases (20.0%). Mean no of re-excisions 1.67 cm, SD 0.84. Six sequential anthracycline/taxane cycles were administered in 17 cases while three cases received anthracycline based chemotherapy only. Median duration of followup from diagnosis was 48 months ranging between 8 months and 144 months. There were two demises at 48 months and 36 months follow up. CONCLUSION: Extended chemotherapy sessions alongside re-excisions were successful in achieving much enhanced rates of pathologically complete remissions at 100% in this yet early report, thus improving breast conservation rates even for T3 and T4 tumours. Our study reports higher PCR rates.

The predictive value of serum soluble E-cadherin levels in breast cancer patients undergoing preoperative systemic chemotherapy.

OBJECTIVES: To date, no reliable markers are available to predict response to or to assess prognosis after preoperative systemic chemotherapy (PST) in patients with locally advanced breast cancer. Previous studies demonstrated that elevated levels of soluble E-cadherin (sE-cadherin), a product of proteolytic cleavage of cell surface E-cadherin, are associated with higher risk for metastatic disease and poor prognosis in various tumor types. We, therefore, hypothesized that serum sE-cadherin levels measured before PST may correlate with pathological response. DESIGN AND METHODS: In a retrospective analysis, sE-cadherin levels were measured in sera of 108 female patients with histologically proven breast cancer before initiation of PST by using a commercially available quantitative sandwich enzyme immunoassay technique. Patients received a median number of 4 (range 3-6) cycles of anthracyline-based chemotherapy. The median patient age was 51.5 (range 21-71) years. Tumor size was measured clinically and translated into the tumor-node-metastasis (TNM)-system before the start of chemotherapy. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score. In univariate analyses the correlations between levels of sE-cadherin and pathological response to PST were calculated. RESULTS: The histopathological regression scores correlated significantly with tumor grading (p=0.045), clinical lymph node status before PST (p=0.031) and sE-cadherin levels (p=0.039). No correlation was seen between histopathological regression scores and hormone receptor and menopausal status as well as Her2-neu status. CONCLUSION: sE-cadherin may be a marker predicting response to PST for patients with breast cancer. Our findings warrant further evaluation of sE-cadherin in a prospective trial.