Clinical Prognostic Stage Research Articles

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate

In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

Validation of the revised 8th AJCC breast cancer clinical prognostic staging system: analysis of 5321 cases from a single institution.

The anatomic stage groups (ASG) have been arguably the most powerful in predicting breast cancer (BC) outcomes. Recognizing the prognostic influence of histologic grade and receptor status, the 8th AJCC mandates their incorporation into the newly established prognostic stage groups (PSG). This staging scheme was subsequently revised to provide pathological and clinical prognostic stage tables (PPSG/CPSG) due to its incapability to categorize a significant subset of BCs, with the former only used for patients having surgical resection as the initial treatment, and the latter for all patients. Given the increasingly used neoadjuvant therapy, PPSG cannot be assigned in a significant proportion of higher staged BCs. In this study, we validated the CPSG in a cohort of 5321 BCs. Compared to ASG, the application of CPSG resulted in assigning 16.1% and 27.2% of cases to a higher or a lower stage group in non-stage IV BCs, respectively. The changes were seen mostly frequently in ASG IB, followed by IIIC, IIB, IIA, IIIA, IIIB, and IA. In 7.9% of cases, the assigned CPSG changed more than one stage group from the ASG. CPSG provided an improved overall discriminating power in predicting BC-specific survival when compared to ASG. Pairwise comparison using the Cox proportional hazard model demonstrated further advantages for CPSG as the latter showed a significant difference in all categories when compared to their proximate groups, except IIA vs. IB and IIIA vs. IIIB. In contrast, a significantly different hazard was only seen when comparing IIB vs. IIA, IIIA vs. IIB, and IV vs. IIIC for ASG. Thus, the revised 8th AJCC CPSG provided a superior overall staging scheme for predicting prognostic outcomes in BC patients receiving standard of care treatment. Further validation using the available data with larger populations and longer follow-up may be needed to refine and improve this table.

Updates in the 8th edition of the TNM staging system for esophagus and esophagogastric junction cancer.

The tumor-node metastasis (TNM) classification, originally developed in 1943 and subsequently adopted by the Union for International Cancer Control and the American Joint Committee on Cancer, is regularly updated based on new information and developments. The TNM classification system is the main tool used for both clinical and pathological staging of cancers worldwide. The 8th edition of the TNM classification for esophageal and esophagogastric junction (EGJ) cancer, released in 2017, was updated from the 7th edition based on additional data supplied by the Worldwide Esophageal Cancer Collaboration group. We summarize the main changes between the 7th and 8th editions of this TNM classification. Notable changes included separate clinical, pathological and pathological prognostic staging for adenocarcinomas and squamous cell carcinomas. Pathological prognostic staging was also improved by updating the T- and N-factors regarding histopathological differentiation and tumor location, respectively. The definition of EGJ cancer was changed from tumors centered within 5cm to tumors within 2cm of the EGJ. These updates to the TNM classification will help to improve the personalized management and treatment of patients with esophageal and EGJ cancers.

The comparison of the anatomic stage and pathological prognostic stage according to the AJCC 8th edition for the prognosis in Japanese breast cancer patients: data from a single institution

BackgroundThe TNM system, which reflects the anatomical extent of disease, was used for stage definition. In the recently published AJCC 8th edition, the new staging system of the clinical and pathological prognostic stage, which incorporates biological factors, is introduced.Patients and methodsA total of 2622 patients with primary breast cancer at stage I–III were included in this study. The anatomic stage (aStage) and the pathological prognostic stage (ppStage) for each case were determined according to the definition of the AJCC 8th edition, and the influence of these stages on the prognosis was compared.ResultsThe stage distributions of aStage and ppStage were as follows: aStage, stage IA (54.8%), IB (1.1%), IIA (26.1%), IIB (9.2%), IIIA (5.6%), IIIB (0.1%), and IIIC (3.1%); and ppStage, stage IA (66.6%), IB (13.1%), IIA (11.1%), IIB (3.2%), IIIA (3.3%), IIIB (1.4%), and IIIC (1.2%). Compared with the aStage, the ppStage stayed the same in 1710 patients (65.2%), was downstaged in 778 patients (29.7%), and was upstaged in 134 patients. The pathological tumor size (pT2) and lymph node metastasis (pN1) were associated with downstaging, and histological grade 3 was associated with upstaging. ER positivity, PgR positivity, and HER2-positivity were significantly associated with downstaging, and the TN subtype was associated with upstaging. Both the aStage and ppStage were significantly associated with the prognosis; however, the Kaplan–Meier curves for the relapse-free survival (RFS), distant recurrence-free survival (DRFS), and overall survival were better stratified by the ppStage.ConclusionThe ppStage reflects the prognosis of patients with early breast cancer more accurately than the aStage.

Abstract P5-06-10: Validation of prognostic stage and anatomic stage in the American joint committee on cancer 8th edition for inflammatory breast cancer

Abstract Background: The American Joint Committee on Cancer (AJCC) recently updated its breast cancer staging system to incorporate biological factors, including estrogen and progesterone receptor (ER, PR), and HER2 status, in the new “prognostic stage” in addition to the traditional TNM anatomic stage. For the clinical anatomic staging, IBCs are classified at T4d; N0-2 as IIIB; and N3 as IIIC. For the clinical prognostic staging, ER+/PR+/HER2+/grade1-2 staged as IIIA; ER+/PR-/HER2-/grade3, ER-/PR+/HER2-/grade3, and all triple-negative cancers staged as IIIC; and all others as IIIB. We undertook this study to validate the clinical prognostic and anatomic stages for inflammatory breast cancer (IBC), an aggressive subgroup. The prognostic staging system, which was developed using non-IBC data, has not been validated in IBC. Methods: We established two cohorts of IBC patients diagnosed without distant metastasis: (1) patients treated at MD Anderson Cancer Center between 1989 and 2017 (MDA-cohort) and (2) patients registered in the SEER database between 2010 and 2015 (SEER-cohort). Survival endpoints including overall survival (OS), and disease-free survival (DFS) were calculated by the Kaplan-Meier method. Breast cancer-specific survival (BCSS) was calculated by the competing risk analysis. The log-rank test was used to compare differences in endpoints between staging groups. The Harrell concordance index (C index) was used to quantify staging models’ predictive performance. A higher C index indicates a better predictive performance. Results: We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage upstaged 248 patients (28%) and downstaged 146 (16%) comparing with the anatomic stage. The prognostic stage showed significant predictive power for BCSS, OS, and DFS (all P<0.0001), although the anatomic stage did not. The C index was significantly higher in the prognostic stage than the anatomic stage for BCSS (0.643 vs. 0.526, P<0.0001), OS (0.641 vs. 0.533, P<0.0001) and DFS (0.599 vs. 0.494, P<0.0001). In the SEER cohort, the prognostic stage upstaged 117 patients (27%) and downstaged 73 (17%). The survival differences between staging groups were more prominent with prognostic stage than with anatomic stage. The C index was significantly higher in the prognostic stage than the anatomic stage for BCSS (0.685 vs. 0.550, P=0.0028) and OS (0.681 vs. 0.557, P=0.0008). In both cohorts, prognostic stage IIIA patients had the best survival rates with the 5-year BCSS of 83% in the MDA cohort and 100% in the SEER cohort. Conclusions: The prognostic stage incorporating biological factors provided more accurate prognostication for IBC patients than the anatomic stage. Our results show that the 8th edition AJCC prognostic staging system is optimal for prognostification in IBC. Citation Format: Kumiko Kida, Kenneth R Hess, Bora Lim, Toshiaki Iwase, Sudpreeda Chainitikun, Maryanne E Sapon, Vicente Valero, Anthony Lucci, Carisa Le-Petross, Wendy A Woodward, Savitri Krishnamurthy, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno. Validation of prognostic stage and anatomic stage in the American joint committee on cancer 8th edition for inflammatory breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-10.

Validation of Prognostic Stage and Anatomic Stage in the American Joint Committee on Cancer 8th Edition for Inflammatory Breast Cancer

Purpose: The American Joint Committee on Cancer recently updated its breast cancer staging system to incorporate biological factors in the “prognostic stage.” We undertook this study to validate the clinical prognostic and anatomic stages for inflammatory breast cancer (IBC). Methods: We established two cohorts of IBC diagnosed without distant metastasis: (1) patients treated at The University of Texas MD Anderson Cancer Center between 1991 and 2017 (MDA cohort) and (2) patients registered in the SEER database between 2010 and 2015 (SEER cohort). For clinical anatomic staging, all IBCs were classified as T4d; N0-2 was staged as IIIB; and N3 was staged as IIIC. For clinical prognostic staging, estrogen receptor (ER)+/ progesterone receptor (PR)+/HER2+/grade 1-2 was staged as IIIA; ER+/PR-/HER2-/grade 3, ER-/PR+/HER2-/grade 3, and all triple-negative cancers were staged as IIIC; and all others as IIIB. Survival endpoints were breast cancer-specific survival (BCSS), overall survival (OS), and disease-free survival (DFS). The Harrell concordance index (C index) was used to quantify staging models’ predictive performance. Results: We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage showed significant predictive power for BCSS, OS, and DFS (all P <0.0001), although the anatomic stage did not. In both cohorts, C index was significantly higher in the prognostic stage than the anatomic stage for all endpoints. Prognostic stage IIIA patients had the best survival rates with the 5-year BCSS of 83% in the MDA cohort and 100% in the SEER cohort. Conclusions: The prognostic stage incorporating biological factors provided more accurate prognostication for IBC than the anatomic stage. Our results show that the prognostic staging system is applicable in IBC. Funding Statement: This research was supported by the Morgan Welch Inflammatory Breast Cancer Research Program, State of Texas Rare and Aggressive Breast Cancer Research Program Grant, and NIH/NCI grant P30 CA016672 (Cancer Center Support Grant– Bioinformatics Shared Resource, Sequencing and Microarray Facility). Declaration of Interests: The authors stated there were no disclaimers. Ethics Approval Statement: The institutional review board approved this study (protocol number PA18-0455). Informed consent was waived for this retrospective analysis.

Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

BACKGROUND:Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy.MATERIALS AND METHODS:One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A.RESULTS:Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer.CONCLUSION:No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients

Comparison between the american joint committee on cancer (ajcc) anatomic and prognostic stages for breast cancer

Introduction: The knowledge regarding the biology of breast cancer has grown substantially and resulted in the identification of different breast cancer subtypes based on their molecular profile, which led to an important change in treatment, from a standardized therapy to a personalized one. A panel of experts and AJCC representatives were responsible for preparing the most recent Cancer Staging Manual. The panel recognized the clinical usefulness of biological factors such as histological grade, expression of hormone receptors (HR; estrogen and progesterone) and overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2) in predicting patient survival7 and incorporated data regarding these biomarkers in the new staging system. In addition, for eligible cases, the ‘Recurrence score’ was also incorporated, generated by the analysis of OncotypeDx (genomic test). The new manual, therefore, started to use 3 stagings. Anatomical staging – based on the classic TNM; clinical prognostic staging and pathological prognosis – association of TNM with prognostic biomarkers (using clinical data in the first and data after surgical treatment in the second). Objective: To verify the agreement between anatomical staging from the 7th edition of the AJCC manual and the prognosis from its 8th edition in a cohort of breast cancer patients at the Hospital do Servidor Público Estadual de São Paulo. Methodology: Observational and cross-sectional study, which evaluated patients undergoing surgical treatment at Hospital do Servidor Público Estadual from March, 2014 to March, 2019. Information was collected regarding age, menopausal status, tumor characteristics, anatomical and clinical staging, neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy, and type of surgery performed. Patients were staged using the digital platform “TNM8 Breast Cancer Calculator”. Results: 805 patients were included in the analysis. All patients were females aged between 29 and 97 years, mostly in the post-menopausal period (78.88%). 74.04% of cases were positive for ER, 66.21% PR-positive, and 88.07% HER2-negative. Prognostic staging downgraded a total of 285 out of 805 patients (35.4%). Almost all of the cases that decreased in staging were ER and/or PR+ (283 of 285). Most of those who went up were Triple Negatives (100 out of 111). Conclusion: Prognostic Staging changes the staging in almost half of the cases and there was a greater number of decreased staging in total and an association of increased staging with tumors considered to have a worse prognosis, which is in agreement with several studies already carried out since the new manual came out.

Risk stratification according to stage and pathology

Stage and pathology are the essential foundation of early breast cancer risk stratification upon which we build, with advances since the last St. Gallen International Breast Cancer Conference. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual made a notable update for breast cancer staging, introducing Clinical and Pathological Prognostic Stages. Two of the most meaningful research advances concerning risk stratification were stage- and pathology-based. The clinical utility of achieving pathological complete response (pCR) after preoperative neoadjuvant systemic therapy versus residual disease, with residual disease defining a high-risk population that can benefit from escalation of adjuvant therapy, was borne out by recent trial results. The strength of evidence of the prognostic role of the morphological assessment of stromal tumor infiltrating lymphocytes (sTILs) increased, robustly demonstrated in triple-negative breast cancer.Presented at the St. Gallen International Breast Cancer Conference.

Staging for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy: Utility of Incorporating Biologic Factors.

The American Joint Committee on Cancer (AJCC) breast cancer pathological prognostic stage, which incorporates biologic factors, was developed using data from patients undergoing upfront surgery, and its application in patients receiving neoadjuvant chemotherapy (NAC) is unknown. We previously developed the Neo-Bioscore, incorporating clinical and pathological TNM categories with biologic factors, to improve the prognostic stratification of NAC patients. This study was undertaken to evaluate the use of available staging models incorporating biologic factors in NAC patients. Patients treated with NAC between 2005 and 2012 at MD Anderson (n = 2363) were staged using the Neo-Bioscore and the AJCC 8th edition: (1) clinical anatomic stage; (2) pathological anatomic stage; (3) clinical prognostic stage; and (4) pathological prognostic stage. Five-year disease-specific survival (DSS) and overall survival (OS) rates, along with Harrell's concordance index (C-index), were estimated. A National Cancer Database (NCDB) cohort (n = 12,887) treated with NAC between 2010 and 2013 was used for validation. In the MD Anderson cohort, staging systems incorporating biologic factors better predicted DSS (bias-corrected C-index: pathological prognostic stage = 0.8026; Neo-Bioscore = 0.7483) and OS (bias-corrected C-index: pathological prognostic stage = 0.7780; Neo-Bioscore = 0.7260) than those using anatomic factors only. Similar results were seen in the NCDB cohort. In pairwise comparisons, the pathological prognostic stage was significantly better (p < 0.0001) than other staging systems in all comparisons except for OS in the NCDB cohort, where it was not significantly different than the Neo-Bioscore (p = 0.2). Biologic factors are important for determining prognosis in patients receiving NAC. These data indicate that the 8th edition AJCC pathological prognostic stage is applicable in these patients.

A retrospective analysis on the prognostic evaluation of triple-negative breast cancer with prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition

Objective: To investigate the clinical relevance of prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition for evaluation of the prognosis of triple-negative breast cancer. Methods: The clinical data of 293 patients with triple-negative breast cancer who were treated at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2014, were retrospectively analyzed. All patients were female, with age of 53(16) years (M(Q(R))). The patients were staged according to the AJCC Breast Cancer Staging System, Eighth Edition. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The role of clinical staging and prognostic staging in prognostic evaluation was investigated. Results: In all, 293 patients with triple-negative invasive breast cancer with complete clinical data and follow-up data were treated over a 7-year period. The follow-up time was 64.5(32.8) months, the 5-year overall survival (OS) rate was 83.9%, and the 5-year disease-free survival (DFS) rate was 84.1%. The results showed that clinical staging and prognostic staging were correlated with the DFS rate and OS rate of patients with triple-negative breast cancer (χ(2) were 15.395 to 50.084,P=0.00). However, these two staging systems yielded different results. The prognostic stage of 91.8%(269/293) patients was higher than that of the original anatomical stage. There were significant differences in disease-free survival rate (χ(2)=22.357,P=0.00) and overall survival rate (χ(2)=50.084, P=0.00) among patients with different clinical stages. There were significant differences in disease-free survival rate (χ(2)=15.395,P=0.00) and overall survival rate (χ(2)=29.187,P=0.00)among patients with different prognostic stages. Conclusions: The prognostic stage according to the AJCC Breast Cancer Staging System, Eighth Edition complements the clinical stage. It has a good predictive value for the prognosis of triple-negative breast cancer.

Abstract P1-03-03: Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer

Abstract Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer has redefined breast cancer staging to better represent the heterogeneity of the disease. The previously established TNM system reflected only tumor size (T), nodal status (N), and distant metastasis (M). The updated staging system introduces new clinical and pathological prognostic staging systems by incorporating tumor grade, tumor markers, and genomic assays. Prospective comparisons of staging assignment between AJCC 7th and 8th edition staging systems have not been performed in the United States. The objective of this study was to compare subjects' assigned stage between the AJCC 7th and 8th edition staging systems. Methods: Data were collected from patients with non-metastatic breast carcinoma who presented to the University of Chicago between January 1, 2018 and May 31, 2018. Upstaging or downstaging was defined as an increase or decrease by one or more letter or number stages (i.e. from IIA to IIB or IB). Descriptive data were generated for all collected data. Analysis was performed in Stata 14.0. Results: Clinical anatomic and prognostic stages were assigned to 246 patients while pathologic anatomic and prognostic stages were assigned to 142 patients. Forty-seven patients underwent neoadjuvant therapy and were not assigned a pathologic prognostic stage, while 57 patients had not undergone surgery at our institution by the end of the study period and were not assigned a pathologic stage. Two patients had lobular carcinomia in situ and were no longer considered to have a malignancy by the 8th edition staging system; anatomic staging was otherwise unchanged from 7th edition to 8th edition staging in this cohort. Of the 246 patients assigned clinical anatomic and prognostic stages, 48 patients were upstaged (19.5%), 37 were downstaged (15.0%), and 161 were not affected (65.5%) by prognostic staging. Of the 142 patients assigned pathologic anatomic and prognostic staging, nine patients were upstaged (6.3%), 32 were downstaged (22.5%), and 101 were not affected (71.1%) by prognostic staging. Four patients were eligible to be downstaged in pathologic prognostic staging by genomic assays such as Oncotype (consisting of Stage 1B or higher patients with T1N0M0 HER2 - ER + PR - Grade 3 disease or T2N0M0 HER2 - ER + disease). Of these patients, three had genomic assays performed by the end of the study period. Results from genomic assays did not affect the staging of these three patients. Stage Changes with the AJCC 8th Edition Upstaged % (n)Downstaged % (n)No Change in Stage % (n)Clinical Stage19.5 (48)15.0 (37)65.5 (161)Pathologic Stage6.3 (9)22.5 (32)71.1 (101) Conclusions: Approximately one third of breast cancer patients were assigned new clinical or pathologic stages with the AJCC 8th edition staging system. These findings confirm that implementation of the new criteria for staging will be important to many patients in discussions of treatment and prognosis. Citation Format: Brian R, Tseng J, Bao J, Jaskowiak N. Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-03.

Introduction of a New Staging System of Breast Cancer for Radiologists: An Emphasis on the Prognostic Stage.

In 2017, the American Joint Committee on Cancer announced the 8th edition of its cancer staging system. For breast cancer, the most significant change in the staging system is the incorporation of biomarkers into the anatomic staging to create prognostic stages. Different prognostic stages are assigned to tumors with the same anatomic stages according to the tumor grade, hormone receptor (estrogen receptor; progesterone receptor) status, and HER2 status. A Clinical Prognostic Stage is assigned to all patients regardless of the type of therapy used; in contrast, a Pathologic Prognosis Stage is assigned to patients in whom surgery is the initial treatment. In a few situations, low Oncotype DX recurrence scores can change the prognostic stage. The radiologists need to understand the importance of the biologic factors that can influence cancer staging.

Comparison of AJCC Anatomic and Clinical Prognostic Stage Groups in Breast Cancer: Analysis of 3322 Cases From a Single Institution

BackgroundThe American Joint Committee on Cancer anatomic stage/prognostic group template arguably is the most powerful in predicting breast cancer outcomes because it considers the primary tumor, regional lymph node involvement, and presence of distant metastasis. However, other tumor and host characteristics have also been proved to be of prognostic value, including histologic grade and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. Thus, the 8th edition of the American Joint Committee on Cancer consolidated these factors into clinical prognostic stage groups. Materials and MethodsWe validated the clinical prognostic stage groups compared with the anatomic stage groups in a cohort of 3322 breast cancer patients. ResultsCompared with the anatomic stage, application of the clinical prognostic stage assigned 27.7% and 24.7% of cases to higher and lower stage groups, respectively. In 14% and 2.8% of cases, the assignment of clinical prognostic stage varied by 2 and 3 anatomic stages up or down, respectively. The Cox proportional hazard model demonstrated superior discriminatory power for clinical prognostic stage (overall χ2, 464.5; P < .0001 vs. χ2, 363.9; P < .0001). A pairwise comparison revealed that significant improvement was especially observed for patients with clinically prognostic stage I and III disease compared with that of the anatomic stage groups. ConclusionThe new clinical prognostic stage provides a more powerful, yet imperfect, tool for predicting breast cancer outcomes. Further refinement of this system might be necessary in the pursuit of precision medicine.

Incorporating Biologic Factors into the American Joint Committee on Cancer Breast Cancer Staging System: Review of the Supporting Evidence.

The American Joint Committee on Cancer staging system has evolved in response to improved imaging, refined surgical techniques, enhanced pathologic evaluation, and greater understanding of tumor biology. The 8th edition has introduced clinical and pathologic prognostic stages for breast cancer that incorporate biologic variables (grade, estrogen/progesterone receptor status, HER2 status, multigene panels) with TNM categories that define the anatomic stage. The prognostic staging system facilitates more refined stratification than the anatomic stage with respect to survival and is an important advance that maintains the clinical relevance of the staging system by taking into account tumor biology and current treatment algorithms.

Changes and Clarifications in the Eighth Edition of the AJCC Cancer Staging System for Breast Cancer

Abstract In the eighth edition of the American Joint Committee on Cancer staging system for breast cancer, the definitions for T (tumor), N (nodes), and M (metastases) remain substantially unchanged but with clarifications for certain categories that may have been problematic for pathologists and clinicians. The principal change is the decision to exclude lobular carcinoma in situ from T classification. In contrast, there is a major change in how stage is determined by introducing a new clinical prognostic stage and a new pathological prognostic stage. These prognostic stages incorporate information about grade, estrogen receptor expression, progesterone receptor expression, human epidermal growth factor receptor 2 expression, and, in some cases, the Oncotype Dx Recurrence Score, in addition to T, N, and M, to create groups of cancers predicted to have a similar survival at 3 years based on information from the National Cancer Database. This review highlights the changes and notable clarifications to the TNM system and how these relate to standard pathology reporting.

Incorporating Biology Into Breast Cancer Staging: American Joint Committee on Cancer, Eighth Edition, Revisions and Beyond.

Higher-quality imaging, refined surgical procedures, enhanced pathologic evaluation, and improved understanding of the impact of tumor biology on treatment and prognosis have necessitated revisions of the AJCC breast cancer staging system. The eighth edition includes clinical and pathologic prognostic stages that incorporate biologic variables-grade, estrogen and progesterone receptor status, HER2 status, and multigene panels-with the anatomic extent of disease defined by tumor, node, and metastasis categories. The prognostic staging systems facilitate more refined stratification with respect to survival than anatomic stage alone. Because the prognostic staging systems are dependent on biologic factors, accuracy is dependent on rigorous pathologic evaluation of tumors and on administration of treatment dictated by tumor biology. It is anticipated that technological advances will facilitate even more refined determination of underlying biology within tumors and in the peripheral blood, which increasingly is being evaluated as a compartment that reflects the primary tumor and sites of distant metastases. Diseases should be staged according to the eighth edition staging system to accurately reflect prognosis and to allow standardized data collection. Such standardization will facilitate assessment of the impact of advances in diagnosis and treatment of patients with breast cancer.

New and Important Changes in the TNM Staging System for Breast Cancer.

Expanded understanding of biologic factors that modulate the clinical course of malignant disease have led to the gradual integration of biomarkers into staging classifications. The American Joint Committee on Cancer (AJCC) TNM staging system is universally used and has largely displaced other staging classifications for most, although not all, cancers. Many of the chapters of the eighth edition of the AJCC TNM staging system integrated biomarkers with anatomic definitions. The Breast Chapter added estrogen receptor (ER) and progesterone receptor (PR) expression, HER2 expression, and/or amplification and histologic grade to the anatomic assessment of tumor size, regional lymph node involvement, and distant metastases (known as TNM). While preserving an anatomic staging system for continuity and for regions where modern biomarkers are not always available, the eighth edition emphasizes the increased prognostic precision of the clinical prognostic stage groups and the pathologic prognostic stage groups. The clinical prognostic stage groups are applicable to all patients with primary breast cancer before any treatment has been implemented, but require a clinical and imaging evaluation as well as a biopsy with grade and available ER, PR, and HER2 results; the pathologic prognostic stage groups are applicable to all patients treated with complete surgical excision as first treatment and also require a complete pathology report, grade, and ER, PR, and HER2. Applying the pathologic prognostic stage groups to a large database of patients staged by basic TNM groupings changed the stage grouping of almost 40% of patients. Grouping by pathologic prognostic stage groups led to a better prognostic distribution of the group and more precise individual prognostication.

Prognostic Validation of the American Joint Committee on Cancer 8th Staging System in 24,014 Korean Patients with Breast Cancer.

PurposeThe American Joint Committee on Cancer (AJCC) recently released the breast cancer staging system, 8th edition, which included additional four biologic factors. However, there has been no external validation of the prognostic value of the new stages with different population-based databases.MethodsTo validate the prognostic value of the new staging system in the Asian population, with a focus on Korean patients with breast cancer, we performed a retrospective study with data from the Korean Breast Cancer Society that included 24,014 patients with invasive ductal or lobular carcinoma who underwent surgery between January 2009 and January 2012 in Korea. The proportional differences were evaluated between the anatomic staging system (AJCC 7th edition) and the prognostic staging system (AJCC 8th edition, December 2017 published version). Comparisons of overall survival (OS) and disease-free survival (DFS) with Kaplan-Meier graphs and hazard ratios were also performed.ResultsOur analysis included 24,014 patients (median age, 50 years; range, 20–91 years). Stage I, II, and III disease accounted for 47.6%, 43.5%, and 8.9%, respectively, of anatomic stages and 61.8%, 27.6%, and 10.8%, respectively, of clinical prognostic stages. A total of 6,272 cases (26.1%) were upstaged, 4,656 (19.4%) were downstaged, and 13,086 (54.5%) remained unchanged. OS and DFS decreased in the order from prognostic stages IA to IIIC but did not change among the anatomic stage groups.ConclusionOur data suggests that the prognostic staging system provides superior prognostic value to the anatomic staging system in Korean patients with breast cancer.

Cancer biomarker discovery and validation.

With the emergence of genomic profiling technologies and selective molecular targeted therapies, biomarkers play an increasingly important role in the clinical management of cancer patients. Single gene/protein or multi-gene "signature"-based assays have been introduced to measure specific molecular pathway deregulations that guide therapeutic decision-making as predictive biomarkers. Genome-based prognostic biomarkers are also available for several cancer types for potential incorporation into clinical prognostic staging systems or practice guidelines. However, there is still a large gap between initial biomarker discovery studies and their clinical translation due to the challenges in the process of cancer biomarker development. In this review we summarize the steps of biomarker development, highlight key issues in successful validation and implementation, and overview representative examples in the oncology field. We also discuss regulatory issues and future perspectives in the era of big data analysis and precision medicine.