Prognostic value of histopathology, stromal tumor infiltrating lymphocytes (sTILs) and adjuvant chemotherapy (AdjCT) in early stage triple negative breast cancer (TNBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 533-533
Author(s):  
Roberto Antonio Leon-Ferre ◽  
Mei-Yin Polley ◽  
Heshan Liu ◽  
Judith A. Gilbert ◽  
Victoria Cafourek ◽  
...  

533 Background: Current guidelines define TNBC as complete absence of estrogen (ER) and progesterone receptor (PR), without HER2 amplification. However, the prognostic impact of clinical and histopathological factors, sTILs, and AdjCT in TNBC meeting these strict criteria is unknown. Methods: From a cohort of 9985 women who underwent upfront surgery for M0 breast cancer (BC) at Mayo Clinic Rochester from 1985-2012, 1159 pts with ER negative or low (≤10%) BC were identified for central ER/PR/HER2 staining and HER2 FISH (IHC2+ only) to select those with TNBC by modern definitions. Cox proportional hazards models were used to assess the impact of clinicopathological variables on invasive disease-free (IDFS) and overall survival (OS). Results: Tumors from 605 pts (median age 56.3 yrs) met criteria for TNBC (ER < 1%, PR < 1% and HER2 0, 1 or 2+ and FISH negative). 51% were T1, 65% N0, 88% grade 3, and 75% had Ki67 > 15%. Histologically, 39% were anaplastic, 26% invasive ductal, 16% medullary, 8% metaplastic, 6% apocrine and 5% others. Median sTILs was 20% (0-90%). 55% pts received AdjCT [21% anthracycline (A), 19% A + taxane, and 15% other]. Median follow-up for IDFS and OS were 7.4 and 10.6 yrs, respectively. Multivariate analyses demonstrated that higher N stage (p < 0.01), lower sTILs (p = 0.01) and no AdjCT (p < 0.01) were independently associated with worse IDFS and OS. Histology (medullary subtype) was associated with better IDFS in univariate (HR 0.56, 95% CI, 0.35-0.89) but not in multivariate analyses, once sTILs were accounted for. Among systemically untreated pts (n = 182), higher N (p < 0.01) and lower sTILs (p = 0.04) were associated with worse IDFS. For systemically untreated T1N0 pts (n = 111), the 5-yr IDFS was 70% (95% CI, 61-81) [T1a: 83% (95% CI, 63-100), T1b: 68% (95% CI, 52-88) and T1c: 67% (95% CI, 55-83)], compared to 78% (95% CI, 68-84) for T1N0 pts treated with AdjCT. Conclusions: In TNBC pts, N stage, sTILs and receipt of AdjCT were independently prognostic for IDFS and OS. sTILs remained prognostic for IDFS in systemically untreated TNBC. In N0 TNBC, the risk of recurrence or death was substantial in the absence of chemotherapy, even for those with T1 tumors.

2001 ◽  
Vol 19 (6) ◽  
pp. 1671-1675 ◽  
Author(s):  
Shari Gelber ◽  
Alan S. Coates ◽  
Aron Goldhirsch ◽  
Monica Castiglione-Gertsch ◽  
Gianluigi Marini ◽  
...  

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (± SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% ± 3% and 86% ± 4%, respectively. For the matched comparison group survival was 85% ± 3% at 5 years and 74% ± 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P = .04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.


2011 ◽  
Vol 29 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Marianne Ewertz ◽  
Maj-Britt Jensen ◽  
Katrín Á. Gunnarsdóttir ◽  
Inger Højris ◽  
Erik H. Jakobsen ◽  
...  

Purpose This study was performed to characterize the impact of obesity on the risk of breast cancer recurrence and death as a result of breast cancer or other causes in relation to adjuvant treatment. Patients and Methods Information on body mass index (BMI) at diagnosis was available for 18,967 (35%) of 53,816 women treated for early-stage breast cancer in Denmark between 1977 and 2006 with complete follow-up for first events (locoregional recurrences and distant metastases) up to 10 years and for death up to 30 years. Information was available on prognostic factors and adjuvant treatment for all patients. Univariate analyses were used to compare the associations of known prognostic factors and risks of recurrence or death according to BMI categories. Cox proportional hazards regression models were used to assess the influence of BMI after adjusting for other factors. Results Patients with a BMI of 30 kg/m2 or more were older and had more advanced disease at diagnosis compared with patients with a BMI below 25 kg/m2 (P < .001). When data were adjusted for disease characteristics, the risk of developing distant metastases after 10 years was significantly increased by 46%, and the risk of dying as a result of breast cancer after 30 years was significantly increased by 38% for patients with a BMI of 30 kg/m2 or more. BMI had no influence on the risk of locoregional recurrences. Both chemotherapy and endocrine therapy seemed to be less effective after 10 or more years for patients with BMIs greater than 30 kg/m2. Conclusion Obesity is an independent prognostic factor for developing distant metastases and for death as a result of breast cancer; the effects of adjuvant therapy seem to be lost more rapidly in patients with breast cancer and obesity.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 583-583
Author(s):  
Nour Abuhadra ◽  
Ryan Sun ◽  
Jennifer Keating Litton ◽  
Gaiane M Rauch ◽  
Alastair Mark Thompson ◽  
...  

583 Background: Pathologic complete response is an excellent surrogate for disease-free survival (DFS) and overall survival (OS) in TNBC. High sTIL is associated with improved pCR rates in TNBC. Recent data suggest that high sTIL is also associated with improved outcomes in patients who received no chemotherapy for early stage TNBC (Park, Annals of Oncology, 2019). Thus, we hypothesized that high sTIL may have prognostic impact in patients who do not achieve pCR to NAT. Methods: Pretreatment core biopsies from 182 patients with early-stage TNBC enrolled on the ARTEMIS trial (NCT02276443) were evaluated for sTIL by H&E. Patients were stratified according to sTIL (low < 30%, and high > 30%) and pCR (patients with pCR vs. no pCR). The primary outcome measure was DFS, defined from the date of diagnosis to the first local recurrence, distant metastases or death. Cox proportional hazards regression model was used. During follow-up 33 events for DFS were observed. Results: Among subjects who achieve pCR, DFS was excellent regardless of sTIL status and significantly better than those without pCR (p < 0.05). However, patients with high sTIL and no pCR demonstrated significantly worse DFS compared to all subjects having pCR (HR 0.18, 95% CI 0.04-0.76, p = 0.02). Additionally, we did not find a significant difference between high and low sTIL patients who did not achieve pCR. Conclusions: In early TNBC receiving NAT, for patients failing to achieve pCR, high sTIL was not associated with improved DFS; outcomes were comparable to those with low sTIL without pCR. Thus, high sTIL at baseline does not appear to confer an intrinsic prognostic benefit in the absence of pCR.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4142-4142
Author(s):  
Lucy Xiaolu Ma ◽  
Gun Ho Jang ◽  
Amy Zhang ◽  
Robert Edward Denroche ◽  
Anna Dodd ◽  
...  

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2657
Author(s):  
Luca Campedel ◽  
Paul Blanc-Durand ◽  
Asker Bin Asker ◽  
Jacqueline Lehmann-Che ◽  
Caroline Cuvier ◽  
...  

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11524-11524
Author(s):  
Chelain Rae Goodman ◽  
Brandon-Luke L Seagle ◽  
Eric Donald Donnelly ◽  
Jonathan Blake Strauss ◽  
Shohreh Shahabi

11524 Background: Circulating tumor cell (CTC) status has been shown to be prognostic of decreased survival in non-metastatic breast cancer. While up to 20-30% of patients with early breast cancer have detectable CTCs, less is known regarding the role of CTC-status in guiding clinical management. Methods: An observational cohort study was performed on women with stage I breast cancer evaluated for CTCs from the 2004-2014 National Cancer Database. Logistic regression was used to explore clinicopathological associations with CTC-status. Kaplan-Meier and multivariable Cox proportional-hazards survival analyses were used to estimate associations of CTC-status with overall survival using a propensity score-adjusted and inverse probability-weighted matched cohort. Results: Of the stage I breast cancer women evaluated for CTCs, 23.1% (325/1,407) were CTC-positive. Age, histology, receptor status, and nodal stage were associated with CTC-status. CTC-status was an effect modifier of the radiotherapy-survival association: CTC-positive women who did not receive radiotherapy had an increased hazard of death compared to CTC-negative women who also did not receive radiotherapy (four-year survival: 85.7% vs. 93.3%, HR = 2.92, CI = 1.43-5.98, P = 0.003). CTC-positive patients treated with radiotherapy did not have decreased survival compared to CTC-negative patients not treated with radiotherapy (HR = 0.67, CI = 0.28-1.65, P = 0.40). From the matched cohort analysis, CTC-positive women who did not receive radiation had a 4.82-fold increased hazard of death compared to CTC-positive women treated with radiotherapy (four-year survival: 83.2% vs. 96.6%; CI = 2.62-8.85, P < 0.001). Conclusions: Treatment with adjuvant radiotherapy was associated with improved survival in CTC-positive women with stage I breast cancer. If prospectively validated, CTC-status may be valuable as a predictor of benefit of radiotherapy in early stage breast cancer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18155-e18155 ◽  
Author(s):  
Drew Carl Drennan Murray ◽  
Shruti Bhandari ◽  
Phuong Ngo ◽  
Sarah Mudra ◽  
Rachana Shirish Lele ◽  
...  

e18155 Background: Black (B) women after early stage of diagnosis have been shown to have double the risk of white (W) women for failing to receive adjuvant chemotherapy. Despite lower incidence of breast cancer in B patients, they are more likely to die of the disease. Worse outcomes in B populations have been related to clinical and socioeconomic factors. However, the determination of improved access and its effects on survival in black patients remains uncertain. Methods: 1042844 patients diagnosed between 2004 and 2014 with stage I-III breast cancer were identified in the NCDB. Only W and B races were analyzed with established risk factors of age, stage, comorbidity score, and insurance status. Data was analyzed using univariable and multivariable logistic and Cox proportional hazards regression models. Odds Ratio (OR) for binary outcome, Hazard Ratio (HR) for time-to-event (survival) outcome along with 95% confidence interval (95% CI) are reported. Results: Among the total population 85.5% were W, 10.6% B, and 3.9% other. B were more likely to be uninsured (OR: 1.66; 95% CI: 1.59 - 1.72; p < 0.0001), or have Medicaid (OR: 2.01; 95% CI: 1.96 - 2.07; p < 0.0001). B were also diagnosed at later stage (stage 3 OR: 1.59; 95% CI: 1.57 - 1.63; p < 0.0001) with higher co-morbidities (OR: 2.49; 95% CI: 2.34 - 2.67; p < 0.0001) consistent with prior studies. B were more likely to experience delayed treatment (OR: 2.15; 95% CI: 2.10 - 2.20; p < 0.0001). B race remained an independent factor associated with higher likelihood of death compared to W patients (HR: 1.32; 95% CI: 1.3 - 1.34; p < 0.0001) in multivariable analysis. Conclusions: This large database study demonstrates that even when controlling for established risk factors such lack of insurance or Medicaid, higher comorbidities, and later stage at diagnosis, B patients were more likely to experience delays in treatment initiation and worse overall survival. This suggests race remains an independent risk factor for poor outcome even when clinical factors are matched. Further analysis including tumor biology should be examined to better understand this persistent disparity.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19114-e19114
Author(s):  
Jennifer Kay Plichta ◽  
Christel N. Rushing ◽  
Holly C. Lewis ◽  
Dan G. Blazer ◽  
Terry Hyslop ◽  
...  

e19114 Background: National cancer registries are valuable tools used to analyze patterns of care and clinical oncology outcomes; yet, patients with missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). Methods: Using the NCDB and SEER, we compared data missingness among patients diagnosed with invasive breast cancer from 2010-2014. Key variables included: demographic variables (age, race, ethnicity, insurance, education, income), tumor variables (grade, ER, PR, HER2, TNM stage), and treatment variables (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data via Cox proportional hazards models. Results: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missingness of at least 1 key variable was 29% and 13%, respectively. Of those, the majority were missing a tumor variable (NCDB 80%; SEER 88%), while demographic and treatment variables were missing less often. When compared to patients with complete data, missingness was associated with a greater risk of death; NCDB 17% vs. 14% (HR 1.23, 99% CI 1.21-1.25) and SEER 27% vs 14% (HR 2.11, 99% CI 2.05-2.18). Rate of death was similar whether the patient was missing 1 or ≥2 variables. When stratified by the type of missing variable, differences in OS between those with and without missing data in the NCDB were small. In SEER, reductions in OS were largest for those missing tumor variables (HR 2.26, 99% CI 2.19-2.33) or surgery data (HR 3.84, 99% CI 3.32-4.45). Among the tumor variables specifically, few clinically meaningful differences in OS were noted in the NCDB, while the most significant differences in SEER were noted in T and N stage (table). Conclusions: Missingness of select variables is associated with a worse OS and is not uncommon within large national cancer registries. Therefore, researchers must use caution when choosing inclusion/exclusion criteria for outcomes studies. Future research is needed to elucidate which patients are most often missing data and why OS differences are observed. [Table: see text]


2006 ◽  
Vol 24 (28) ◽  
pp. 4611-4619 ◽  
Author(s):  
Xiao-Jun Ma ◽  
Susan G. Hilsenbeck ◽  
Wilson Wang ◽  
Li Ding ◽  
Dennis C. Sgroi ◽  
...  

Purpose We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility. Patients and Methods Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models. Results ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007). Conclusion This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.


2012 ◽  
Vol 30 (36) ◽  
pp. 4493-4500 ◽  
Author(s):  
John M. McLaughlin ◽  
Roger T. Anderson ◽  
Amy K. Ferketich ◽  
Eric E. Seiber ◽  
Rajesh Balkrishnan ◽  
...  

Purpose To determine the impact of longer periods between biopsy-confirmed breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival. Patients and Methods This study was a noninterventional, retrospective analysis of adult female North Carolina Medicaid enrollees diagnosed with breast cancer from January 1, 2000, through December, 31, 2002, in the linked North Carolina Central Cancer Registry–Medicaid Claims database. Follow-up data were available through July 31, 2006. Cox proportional hazards regression models were constructed to evaluate the impact on survival of delaying treatment ≥ 60 days after a confirmed diagnosis of breast cancer. Results The study cohort consisted of 1,786 low-income, adult women with a mean age of 61.6 years. A large proportion of the patients (44.3%) were racial minorities. Median time from biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox proportional hazards regression showed that although Dx2Tx length did not affect survival among those diagnosed at early stage, among late-stage patients, intervals between diagnosis and first treatment ≥ 60 days were associated with significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to 2.77; P = .05) and breast cancer–specific survival (HR, 1.85; 95% CI, 1.04 to 3.27; P = .04). Conclusion One in 10 women waited ≥ 60 days to initiate treatment after a diagnosis of breast cancer. Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients. Interventions designed to increase the timeliness of receiving breast cancer treatments should target late-stage patients, and clinicians should strive to promptly triage and initiate treatment for patients diagnosed at late stage.


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