PO-0739: Role of ki67, tumor size and lymph nodal status as a prognostic index in breast cancer

Context.—The appropriate staging of breast cancers includes an evaluation of tumor size and nodal status. Histologic grade in breast cancer, though important and assessed for all tumors, is not integrated within tumor staging. Objective.—To determine whether the histologic grade remains a prognostic factor for breast cancer regardless of tumor size and the number of involved axillary lymph nodes. Design.—By using a new clustering algorithm, the 10-year survival for every combination of T, N, and the histologic grade was determined for cases of breast cancer obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. There were 36 combinations of TN, defined according to the American Joint Committee on Cancer, and grade. Results.—For each combination of T and N, a categorical increase in the histologic grade was associated with a progressive decrease in 10-year survival regardless of the number of involved axillary lymph nodes or size of the primary tumor. Absolute survival differences between high and low grade persisted despite larger tumor sizes and greater nodal involvement, though trends were apparent with increasing breast cancer stage. Statistical significance depended on the number of cases for each combination. Conclusions.—Histologic grade continues to be of prognostic importance for overall survival despite tumor size and nodal status. Furthermore, these results seem to indicate that the assignment of the histologic grade has been consistent among pathologists when evaluated in a large data set of patients with breast cancer. The incorporation of histologic grade in TNM staging for breast cancer provides important prognostic information.

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High Levels of Cathepsin B Predict Poor Outcome in Patients with Breast Cancer

The International Journal of Biological Markers ◽

10.1177/172460089801300303 ◽

1998 ◽

Vol 13 (3) ◽

pp. 139-144 ◽

Cited By ~ 26

Author(s):

T.M. Maguire ◽

S.G Shering ◽

C.M. Duggan ◽

E.W. McDermott ◽

N.J. O'Higgins ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Plasminogen Activator ◽

Tumor Size ◽

Cathepsin B ◽

Nodal Status ◽

Chi Square ◽

Poor Outcome ◽

Cancer Spread ◽

Er Status

Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and metastasis. Other proteases involved in cancer spread such as urokinase-type plasminogen activator (uPA) and cathepsin D have previously been shown to be prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with primary breast cancer. CB levels were significantly higher in both primary and metastatic breast tumors than in fibroadenomas (p=0.0001). In the primary carcinomas, CB levels showed no significant correlation with either nodal status, tumor size or estrogen receptor (ER) status. Patients with primary breast cancers containing high levels of CB had a significantly shorter disease-free interval (p=0.01, chi-square=6.61) and overall survival (p=0.014, chi-square=6.08) than patients with low levels of the protease. However, in multivariate analysis, using nodal status, tumor size, ER status and urokinase plasminogen activator (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER status and uPA were prognostic in multivariate analysis. In conclusion, CB, like certain other proteases implicated in cancer metastasis, correlates with poor outcome in patients with breast cancer. These results thus support the evidence from model systems linking CB to cancer spread. Inhibition of CB expression or activity might therefore be exploited for anti-metastatic therapies.

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The Numbers of FoxP3+ Lymphocytes in Sentinel Lymph Nodes of Breast Cancer Patients Correlate With Primary Tumor Size but Not Nodal Status

Cancer Investigation ◽

10.3109/07357907.2011.585193 ◽

2011 ◽

Vol 29 (6) ◽

pp. 419-425 ◽

Cited By ~ 12

Author(s):

Raavi Gupta ◽

James S. Babb ◽

Baljit Singh ◽

Luis Chiriboga ◽

Leonard Liebes ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Cancer Patients ◽

Tumor Size ◽

Primary Tumor ◽

Sentinel Lymph Nodes ◽

Nodal Status ◽

Breast Cancer Patients ◽

Primary Tumor Size

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Late relapse associated with CEP 17 polysomic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20011 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20011-20011

Author(s):

L. J. Theobald ◽

S. Dobin ◽

S. Beeran ◽

D. Miltenburg ◽

H. Rajab ◽

...

Keyword(s):

Breast Cancer ◽

Gene Amplification ◽

Tumor Size ◽

Nodal Status ◽

Gene Copy ◽

Categorical Variables ◽

Late Relapse ◽

Study Cohort ◽

Breast Cancers ◽

Clinicopathologic Factor

20011 Background: The clinicopathologic features associated with chromosome enumeration probe 17 (CEP 17) polysomy by fluorescence in situ hybridization (FISH) are not well defined. CEP 17 polysomy is frequently encountered in assessing Her-2neu amplification, which has become an important adjuvant therapeutic target. One mechanism to increase Her-2neu gene copy is polysomy. In this analysis the prognostic and predictive factors associated with CEP 17 polysomy are compared to similar factors in Her-2neu gene amplification. Methods: All cases of Her-2neu gene amplification and CEP 17 polysomic breast cancers from 2000 to present were abstracted. The polysomy group was defined as at least 3 gene copies and was further subdivided into two groups; 3–4 copies and ≥ 5 copies. This resulted in 193 cases of invasive breast cancer, which became the study cohort. Polysomic status and her-2neu gene amplification was compared to age, estrogen receptor (ER), progesterone receptor (PR), grade, tumor size, cell type, mitotic rate, nodal status, number of positive nodes and relapse. Descriptive statistics were used for categorical variables. The χ2 test was used to compare each clinicopathologic factor. Results: Both the ER and PR status was significantly different in the 3 groups. For the Her-2neu amplified, the polysomic 3–4, and the polysomic ≥ 5, the ER positive status was 53%, 67% and 81%, respectively (p = .012). Histologic grade, tumor size and nodal status were not significantly different between groups. Lobular pathology was present in 15% of the polysomy ≥ 5 group, 8% of the polysomy 3–4 group and 1.7% of the amplified group and this difference was significant (p = .03). Relapse disease status was significantly more frequent in the polysomy ≥ 5 group (18.5%) compared to the amplified group (2.6%) (p = .007). Within the relapsed group the median time to relapse was 4 years for the amplified patients versus 12 years and 10 years for the polysomic patients. Conclusion: The incidence of CEP 17 polysomy varies in the literature from 10–50% depending on definitions. Our study is unique in that we divided the polysomic group into 3–4 copies which can be complicated by proliferative activity versus ≥ 5 copies. A significant association between relapse and polysomic breast cancer is described in our dataset. No significant financial relationships to disclose.

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SEER study of breast cancer specific mortality (BCSM) in patients with lobular tumors treated based on recurrence score results.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.11568 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 11568-11568

Author(s):

Frederick L. Baehner ◽

Steven Shak ◽

Dave P. Miller ◽

Valentina I. Petkov

Keyword(s):

Breast Cancer ◽

Tumor Size ◽

Multivariable Analysis ◽

Recurrence Score ◽

Tumor Grade ◽

Nodal Status ◽

Large Sample Size ◽

Lobular Breast Cancer ◽

Gene Assay ◽

Actuarial Methods

11568 Background: Linking the 21-gene assay RS result to the SEER Registries demonstrated very low 5-y BCSM with low RS and high 5-y BCSM with high RS across subgroups, such as nodal status, age, tumor size and grade (npj Breast Cancer 2016). Given the large sample size and interest in outcomes as a function of tumor characteristics, we characterized the relationship between RS results and BCSM in patients reported by SEER with lobular morphology. Methods: Patients with RS and lobular morphology based on the registry ICD-O-3 code 8520 were eligible if node negative (N0) or node positive up to 3 positive nodes (N+mic,1-3), HR+, HER2- negative, no prior malignancy, and diagnosed between Jan 2004 and Dec 2012. No information in SEER is available regarding lobulars, ie., trabecular, alveolar, solid and pleomorphic. 5-y BCSM was estimated using actuarial methods. Results: There were 6,075 eligible patients reported with lobular morphology (11% of cases). Median age was 59 years; 88%/12% were N0/N+; 31%/62%/7% grade 1/2/3; 61%/39% ≤2 cm/>2 cm. Median follow-up was 44 months. A minority (8%) had RS >25. Chemotherapy (CT) use and BCSM increased with increasing RS. In multivariable analysis in N0 disease, continuous RS result and tumor size predicted BCSM (p=0.003 and p=0.04, respectively), whereas age and tumor grade were non-significant. In multivariable analysis in N+ disease, continuous RS result alone predicted BCSM (p=0.002). Conclusions: In these analyses the prognosis of patients with lobular breast cancer treated based on RS results depends on both nodal status and the RS result. The 5-y BCSM for lobular breast cancer is excellent with RS of 25 or less, and increases for RS >25. [Table: see text]

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The Role of Axillary Ultrasound in Determining Nodal Status in Patients with Early Breast Cancer Undergoing Sentinel Node Biopsy: Are there Other Factors Which Should be Considered?

International Journal of Surgery ◽

10.1016/j.ijsu.2010.07.016 ◽

2010 ◽

Vol 8 (7) ◽

pp. 516

Author(s):

E. Aitken ◽

I. Roy ◽

E. El-Tahir

Keyword(s):

Breast Cancer ◽

Sentinel Node ◽

Sentinel Node Biopsy ◽

Early Breast Cancer ◽

Nodal Status ◽

Axillary Ultrasound ◽

Node Biopsy

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PREDICTIVE RELAPSE MODEL IN PATIENTS WITH LUMINAL HER2-NEGATIVE BREAST CANCER

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2020-4-61-73 ◽

2020 ◽

pp. 61-73

Author(s):

M.Kh. Torosyan ◽

T.V. Shevchenko ◽

V.V. Rodionov ◽

Yu.G. Savinov ◽

Yu.A. Veryaskina ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Model ◽

Prognostic Index ◽

Cancer Recurrence ◽

Disease Stage ◽

Luminal Breast Cancer ◽

Her2 Overexpression ◽

Ki 67 ◽

Expression Levels

Luminal HER2-negative breast cancer (BC) detected at early stages is characterized by a relatively favorable course. However, in some cases, there may be a relapse of the disease regardless of the treatment. The aim of the study was to identify predictors of recurrence of primary resectable luminal HER2-negative breast cancer. Materials and Methods. The authors examined biopsies of patients’ breast tumors (n=158) with luminal HER2-negative breast cancer, stage T1-2N0-1M0, as well as anamnestic data of patients. All women were divided into 2 groups: with disease recurrence within the next 5 years after surgery (n=53) and relapse-free patients (n=105). Macroscopic tumor characteristics, its malignancy, total malignancy score, Nottingham prognostic index, Ki-67, expression of receptors for estrogen and progesterone and their influence on relapse were studied. The authors analyzed expression levels of miRNA (miRNA-21, miRNA-221, miRNA-222, miRNA-155, miRNA-205, miRNA-20a, miRNA-125b, miRNA-146b, miRNA-200a) in tumor tissues. Statistical data processing was performed using Statistica 7 (StatSoft Inc., USA) and MedCalc (version 15.2) software. Results. Comparative analysis of miRNA expression levels between groups of patients with recurrent breast cancer (n=21) and relapse-free patients (n=20) revealed a statistically significant increase in the expression levels of miRNA-21, miRNA-205, miRNA-146b, and miRNA-200a in the group with recurrent disease. The authors established the predictive role of the ratios of the expression levels of potentially oncogenic and tumor suppressive miRNA-21/miRNA-155 and miRNA-21/miRNA-205, as well as the role of miRNA-20a in breast cancer recurrence in combination with Ki-67, disease stage, and primary tumor size. Based on the data obtained, they developed a prognostic model to determine the recurrence of primary operable luminal HER2-negative breast cancer. Conclusion. The created prognostic model allows to clearly stratify the prognosis of primary operable luminal HER2-negative breast cancer. Keywords: primary resectable luminal breast cancer without HER2 overexpression, recurrence prognosis, miRNA. Люминальный HER2-негативный рак молочной железы (РМЖ), выявленный на ранних стадиях, характеризуется относительно благоприятным течением. Однако в ряде случаев возникает рецидив заболевания независимо от проведенного лечения. Цель исследования – выявить предикторы рецидивирования первично операбельного люминального HER2-негативного РМЖ. Материалы и методы. Исследовались биоптаты опухолей молочной железы пациенток (n=158) с люминальным HER2-негативным РМЖ стадии T1-2N0-1M0, а также анамнестические данные пациенток. Все женщины были разделены на 2 группы: с рецидивом заболевания в течение последующих 5 лет после проведения операции (n=53) и с безрецидивным течением (n=105). Изучены макроскопические характеристики опухоли, степень злокачественности, суммарный балл злокачественности, Ноттингемский прогностический индекс, Ki-67, экспрессия рецепторов к эстрогену и прогестерону и их влияние на возникновение рецидива. Проведен анализ уровней экспрессии миРНК (миРНК-21, миРНК-221, миРНК-222, миРНК-155, миРНК-205, миРНК-20а, миРНК-125b, миРНК-146b, миРНК-200a) в тканях опухолей. Статистическая обработка данных произведена с помощью программ Statistica 7 (StatSoft Inc., США) и MedCalc (версия 15.2). Результаты. Сравнительный анализ уровней экспрессии миРНК между группами пациенток с рецидивом РМЖ (n=21) и безрецидивным течением (n=20) выявил статистически значимое повышение уровней экспрессии миРНК-21, миРНК-205, миРНК-146b и миРНК-200a в группе с рецидивом заболевания. Установлена предсказывающая роль соотношений уровней экспрессии потенциально онкогенных и онкосупрессорных миРНК-21/миРНК-155 и миРНК-21/миРНК-205, а также роль миРНК-20a в возникновении рецидива РМЖ в сочетании с Кi-67, стадией заболевания, размером первичной опухоли. На основе полученных данных разработана прогностическая модель определения рецидива первично операбельного люминального HER2-негативного РМЖ. Выводы. Созданная прогностическая модель позволяет четко стратифицировать прогноз первично операбельного люминального HER2-негативного РМЖ. Ключевые слова: первично операбельный люминальный рак молочной железы без гиперэкспрессии HER2, прогноз рецидива, миРНК.

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Prognostic significance of p53 overexpression in luminal HER2-negative type breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.35 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 35-35 ◽

Cited By ~ 1

Author(s):

Shoichi Kikuchi

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Tumor Size ◽

Prognostic Significance ◽

Nodal Status ◽

Nuclear Grade ◽

P53 Overexpression ◽

Negative Type ◽

Luminal Type ◽

Significant Factors

35 Background: In this study, we evaluated the prognostic significance of p53 overexpression, because it was reported that there was a significant correlation between p53 and resistance to endocrine therapy, and prognosis. Methods: A retrospective analysis was performed using 2,332 primary breast cancer patients who underwent surgery between 2001 and 2010. There were 1,899 cases with luminal subtypes (905 cases: HER2-negative and Ki67 low type; 808 cases: HER2-negative and Ki67 high type; and, 186 cases: HER2-positive type), 155 cases with HER2-enriched subtypes, and 278 cases with triple-negative subtypes. Luminal type was defined as ER-positive cell rates ≥ 1%, regardless of PgR status. The cut-off value of the Ki67 index was 20%. Moreover, tumor size, nodal status and nuclear grade were studied in relation to disease free (DFS) and overall survival (OS) using the Cox proportional hazard model. Results: We found that p53 overexpression was present in 10% of the patients and significantly correlated with larger tumors, younger age, positive nodes, a higher grade, negative ER/PgR, a higher Ki67, and positive HER2. The patients with p53 overexpression had significantly unfavorable prognosis, especially in the patients who only received endocrine therapy. There were 26 cases in the luminal HER2 negative and Ki67 low type group that had p53 overexpression and showed a significantly shorter DFS. In the univariate analysis for DFS, p53, Ki67, tumor size, nuclear grade and nodal status were significant factors in luminal HER2 negative type. In the subsequent multivariate analysis for DFS, the p53 status was one of the most significant factors. Conclusions: The p53 overexpression was a significant prognostic factor in luminal type breast cancer. Therefore, the prognostic evaluation of luminal HER2 negative type breast cancer might be improved using an immunopanel, which includes Ki67 and p53. Moreover, it might isolate the patients who are resistant to endocrine therapy.

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