Elevated preoperative serum levels of collagen I carboxyterminal telopeptide predict better outcome in early-stage luminal-B-like (HER2-negative) and triple-negative subtypes of breast cancer

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I–II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081–9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263–12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088–13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354–125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297–15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033–3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.

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Epigenetic aspects of triple-negative in patients with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1041 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1041-1041

Author(s):

Joaquina Martínez-Galan ◽

Sandra Rios ◽

Juan Ramon Delgado ◽

Blanca Torres-Torres ◽

Jesus Lopez-Peñalver ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Dna Methylation ◽

Triple Negative ◽

Breast Cancer Subtype ◽

Regulation Of Gene Expression ◽

Breast Cancer Subtypes ◽

Luminal A ◽

Cancer Subtypes ◽

Luminal B

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p>0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

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Chemosensitivity and endocrine sensitivity prediction by MammaPrint and BluePrint in the Neoadjuvant Breast Registry Symphony Trial (NBRST).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.29 ◽

2014 ◽

Vol 32 (26_suppl) ◽

pp. 29-29

Author(s):

Pat W. Whitworth ◽

Mark Gittleman ◽

Stephanie Akbari ◽

Lisette Stork ◽

Femke De Snoo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Pathologic Complete Response ◽

Complete Response ◽

Excision Biopsy ◽

Luminal A ◽

Neoadjuvant Endocrine Therapy ◽

Cancer Subtypes ◽

Luminal B ◽

Prior Therapy

29 Background: Classification into molecular subtypes is important for the selection of therapy for patients with breast cancer. Previous analyses demonstrated that breast cancer subtypes have distinct clinical outcome (Gluck, BCRT 2013). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathologic complete response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups. Methods: The study includes women aged 18 to 90 with histologically proven breast cancer, who are scheduled to start neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy (NET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. Results: Of 336 patients, T1-4 N0-3, had definitive surgery and the overall pCR rate was 24%. 32/167 (19%) IHC/FISH ERPR+/Her2- patients were reclassified by BluePrint (31 Basal). 43/95 (45%) IHC/FISH Her2+ patients were reclassified by BluePrint (25 Luminal and 18 Basal). 3/74 (3%) IHC/FISH triple-negative patients were not Basal by BluePrint. Of 45 (13%) patients classified as Luminal A 32 received NCT; one patient (3%) had a pCR; 13 patients received NET and 9 (70%) had a PR. Of 116 (35%) patients classified as Luminal B, 111 received NCT and seven (6%) had a pCR. The pCR rate (17/149 (11%)) in IHC/FISH ERPR+/HER2- patients was higher. Fifty-five (16%) are BluePrint HER2 and received NCT (51 plus trastuzumab); 27 (49%) had a pCR compared to 35/95 (37%) in IHC/FISH HER2+ patients. One-hundred twenty (36%) are BluePrint Basal and received NCT; 46 (38%) had a pCR, similar to the pCR percentage seen in the 74 patients designated triple-negative by IHC/FISH. Conclusions: Molecular subtyping using MammaPrint and BluePrint leads to a reclassification of 23% (78/336) of tumors. BluePrint reclassification resulted in better grouping of patients into expected response groups compared to local surrogate subtyping with immunostains.

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Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program

Journal of Medical Screening ◽

10.1177/0969141318816736 ◽

2018 ◽

Vol 26 (3) ◽

pp. 154-161

Author(s):

Linda Perron ◽

Sue-Ling Chang ◽

Jean-Marc Daigle ◽

Nathalie Vandal ◽

Isabelle Theberge ◽

...

Keyword(s):

Breast Cancer ◽

Mammography Screening ◽

Triple Negative ◽

Screening Program ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes ◽

Luminal B ◽

Mammography Screening Program ◽

Screening Sensitivity

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

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Distant disease-free survival (DDFS) discrimination capacity of various pathologic complete response (pCR) definitions according to breast cancer subtypes.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.162 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 162-162

Author(s):

Masaya Hattori ◽

Keitaro Matsuo ◽

Mari Ichikawa ◽

Takashi Fujita ◽

Masataka Sawaki ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Disease Free Survival ◽

Roc Curves ◽

Luminal A ◽

Distant Disease ◽

Free Survival ◽

Cancer Subtypes ◽

Luminal B

162 Background: pCR has been postulated to be correlated with long-term clinical benefits in some subtypes of breast cancer. Here, we analyzed the discriminatory ability and the predictive power of various pCR definitions for distant disease-free survival (DDFS) according to breast cancer subtypes. Methods: We analyzed 326 (114 Luminal A: ER+/PR+/HER2-, 44 Luminal B/HER2-: ER+/PR-/HER2-, 51 Luminal B/HER2+: ER+/PR+ and/or -/HER2+, 51 HER2: ER-/PR-/HER2+, and 66 Triple negative: ER-/PR-/HER2-) non-metastatic breast cancer patients (pts) who had received neoadjuvant chemotherapy at our institution between January 2003 and June 2012. Four pCR definitions were used: ypT0ypN0, ypT0/isypN0, ypT0/isypN0/+, ypT<1micypN0/+. DDFS was estimated by Kaplan-Meier method, and analyzed by log-rank test and Cox proportional hazard model. The receiver operating characteristic (ROC) curves analysis was used for comparing DDFS prediction models with and without various pCR definitions in addition to other covariates (tumor stage, nodal status, BMI, tumor grade, use of trastuzumab) as variables. Results: The pCR rate was comparatively low in Luminal A and high in HER2. 94.1% of HER2 and 74.5% of Luminal B/HER2+ received total 1 year of trastuzumab therapy. In multivariate analysis, no pCR definitions were associated with improved DDFS significantly in Luminal A, Luminal B/HER2-, Luminal B/HER2+ and HER2, whereas each pCR definition was associated with improved DDFS in Triple negative (ypT0ypN0: HR0.12, p=0.043, ypT0/isypN0: HR0.06, p=0.007, ypT0/isypN0/+: HR0.107, p=0.004, ypT<1micypN0/+: HR0.104, p=0.003). In the ROC curves analysis of triple-negative, a DDFS prediction model including pCR defined as ypT0/isypN0 showed the highest accuracy, but low statistical significance (AUC: 0.834 vs.0.749 p=0.076). Conclusions: pCR could discriminate good and poor prognosis groups only in Triple negative and pCR defined as ypT0/isypN0 has the potential to provide better discrimination in this subtype. The predictive power of pCR for long term clinical benefit in other subtypes may not be obvious due to the influence of effective adjuvant therapies.

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Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes

Modern Pathology ◽

10.1038/modpathol.2010.198 ◽

2010 ◽

Vol 24 (2) ◽

pp. 194-200 ◽

Cited By ~ 20

Author(s):

Christopher M Heaphy ◽

Andrea Proctor Subhawong ◽

Amy L Gross ◽

Yuko Konishi ◽

Nina Kouprina ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Luminal B ◽

Her 2

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Clinical subtypes of breast cancer in Thai women: a population-based study of Chiang Mai province

Asian Biomedicine ◽

10.1515/abm-2019-0034 ◽

2019 ◽

Vol 13 (1) ◽

pp. 11-17

Author(s):

Patumrat Sripan ◽

Hutcha Sriplung ◽

Donsuk Pongnikorn ◽

Surichai Bilheem ◽

Shama Virani ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Population Based ◽

Female Breast Cancer ◽

Breast Cancer Subtypes ◽

Chiang Mai ◽

Luminal A ◽

Cancer Subtypes ◽

Luminal B ◽

Female Breast

Abstract Background The change over time of distribution of breast cancer subtypes using population-based data has not been reported. Objective To describe the change over time of the distribution of female breast cancer by clinical subtype among the population in Chiang Mai, Thailand. Methods Data of breast cancer patients from Chiang Mai Cancer Registry, diagnosed from 2004 to 2013 were combined with immunohistochemical status from medical record, and used to describe the proportions of clinical breast cancer subtypes: (1) luminal A-like (ER+/PR+ and HER2-), (2) luminal B-like (ER+/PR+ and HER2+), (3) HER2 (ER- and PR- and HER2+), (4) triple-negative (ER- and PR- and HER2-). The distribution of breast cancer subtypes by age group was also described. Results Among 3,228 female breast cancer cases diagnosed during 2004–2013, the median age was 52 years and most patients presented at the regional stage. The unknown tumor subtype was lower than 25% in the periods 2008– 2009, 2010–2011, and 2012–2013. In those periods, the proportions of luminal A-like were 33%, 36%, and 48%; the proportions of luminal B-like were 14%, 20%, and 16%, the proportions of HER2 were 15%, 14%, and 13%; and the proportions of triple-negative were 16%, 14%, and 13%, respectively. In comparison with other groups, women aged ≥60 years had a significantly higher proportion of luminal A-like (P = 0.001), while women aged <40 years tended to have a higher proportion of triple-negative (P = 0.10). Conclusions The proportion of breast cancer with luminal subtypes is increasing. Thus, in the future, treatment protocols with a variety of hormone therapies should be provided in order to improve efficacy and coverage of treatment for this population.

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Breast Cancer Subtypes among Iraqi Patients: Identified By Their ER, PR and HER2 Status

Journal of the Faculty of Medicine Baghdad ◽

10.32007/jfacmedbagdad.59469 ◽

2018 ◽

Vol 59 (4) ◽

pp. 303-307

Author(s):

Nada A.S. Alwan ◽

Furat N. Tawfeeq ◽

Faisal H. Muallah

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Progesterone Receptors ◽

Breast Cancer Subtypes ◽

Breast Carcinomas ◽

Luminal A ◽

Cancer Subtypes ◽

Luminal B ◽

Her 2

Background: Breast cancer ranks the first among the Iraqi population since three decades and is currently forming a major public health problem being the second cause of death women. Novel management of breast cancer depends upon precise evaluation of their molecular subtypes; identified by Hormone (Estrogen and Progesterone) receptors and HER2 contents of the primary tumor.Objective: To assess the rates of the different molecular breast cancer subtypes in the examined tissue specimens belonging to females diagnosed with breast cancer in Iraq; correlating the findings with those reported in the literature at the regional and global levels.Patients and Methods: This retrospective study documented the findings of tissue biopsy examination belonging to 686 female patients diagnosed with breast cancer. Formalin fixed paraffin-embedded blocks were utilized to assess the availability of Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions through semi quantitative immuno-histochemical staining technique. Breast carcinomas were classified into four main molecular subtypes: Luminal A: ER/PR(+) / HER2(-), Luminal B/Triple Positive: ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative: ER/PR(-) and HER2(-). Other phenotypes included: ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-) / HER2 (-) and ER (-)/PR (+) / HER2 (-).Results: Out of the exanimated cases of breast carcinomas, the registered rates of positive ER, PR and HER2 tumor contents in this study were 67.8%, 65.3% and 29.4% respectively. The main identified phenotype was the Luminal A in 309 cases (45%). That was followed by the Triple Negative in 107 cases (15.6%) and Triple Positive/Luminal B (96 cases, 14%), while 71 cases (10.3%) were HER2 enriched. The corresponding rates of the (E+/P-/H+), (E-/P+/H+), (E+/P-/H-) and (E-/P+/H-) subtypes were 3.1%, 2.0%., 5.7% and 4.2% respectively. Differences in in the expressions of these IHC molecular markers are illustrated among different countries.Conclusions: Due to the displayed variations in the socio-demographic characteristics and biological risk factors among patients in different populations, it is mandatory to identify the molecular marker subtypes of breast cancer expressions in order to assess the impact of management and response to therapy. The routine documentation of their patterns in the cancer registry reports and published research ensures the validity and reliability of the presented clinical data. الخلفية: سرطان الثدي يحتل المرتبة الأولى بين السكان العراقيين منذ ثلاثة عقود، ويشكل حاليا مشكلة صحية رئيسية حيث يعتبر السبب الثاني للوفاة عند النساء. تعتمد أسس العلاج الجديدة لسرطان الثدي على التقييم الدقيق لأنواعها الفرعية الجزيئية و التي تحددها مستويات مستقبلات هرمون (الاستروجين والبروجسترون) ومحتويات HER2 في الورم الرئيسي. الهدف من الدراسة: تقييم معدلات مختلف الأنواع الفرعية لسرطان الثدي الجزيئي في عينات الأنسجة التي تم فحصها والتي تخص الإناث المصابات بسرطان الثدي في العراق؛ وربط النتائج مع تلك المسجلة على الصعيدين الإقليمي والعالمي المرضى والطرق: وثقت هذه الدراسة بأثر رجعي نتائج فحص خزعة الأنسجة التي تنتمي إلى 686 مريضة مشخصة بسرطان الثدي. واستخدمت لتقييم توافر مستقبلات الاستروجين (ER)، مستقبلات البروجسترون (PR) والتعبيرات HER2 من خلال تقنية الطيخ المناعي شبه الكمي. تم تصنيف سرطان الثدي إلى أربعة أنواع فرعية جزيئية رئيسية: Luminal A: ER/PR(+) / HER2(-), Luminal B/Triple Positive: ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative: ER/PR(-) and HER2(-). و انواع اخرى ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-) / HER2 (-) and ER (-)/PR (+) / HER2 (-). النتائج: من بين حالات سرطان الثدي المهددة، كانت المعدلات المسجلة لمحتوى الأورام الموجبة ER, PR و HER2 في هذه الدراسة 67.8٪ و 65.3٪ و 29.4٪ على التوالي. وكان النمط الظاهري المحدد الرئيسي اللمعية A في 309 حالات (45٪). وأعقب ذلك السلبي الثلاثي في 107 حالات (15.6٪) وثلاثية إيجابية / لومينال B (96 حالة، 14٪)، في حين أن 71 حالة (10.3٪) كانت HER2 المخصب. وكانت المعدلات المقابلة من (E + / P- / H +)، (E / P + / H +)، (E + / P- / H-) و (E / P + / H-) فرعية 3.1٪، 2.0٪. ، و 5.7٪ و 4.2٪ على التوالي. وتظهر الاختلافات في التعبير عن هذه العلامات الجزيئية بين مختلف البلدان. الاستنتاجات والتوصيات: نظرا للاختلافات المعروضة في الخصائص الاجتماعية الديموغرافية وعوامل الخطر البيولوجية بين المرضى في مختلف السكان، فمن الضروري تحديد الأنواع الفرعية الجزيئية من تعبيرات سرطان الثدي من أجل تقييم تأثير الاستجابة للعلاج . ان التوثيق الروتيني لأنماط سرطان الثدي في تقارير سجل السرطان والبحوث المنشورة يضمن صحة ودقة البيانات السريرية ذات العلاقة.

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Methylation RE in serum of patients with breast cancer and relation with molecular phenotype and worse prognostic factors.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.224 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 224-224

Author(s):

J. Martínez-Galan ◽

B. Torres-Torres ◽

R. Del Moral ◽

M. I. Núñez ◽

S. Ríos ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Gene Promoter ◽

Therapy Resistance ◽

Her2 Status ◽

Molecular Phenotype ◽

Luminal A ◽

Cancer Subtypes ◽

Luminal B

224 Background: To determine whether Estrogen Receptor (ESR1) (+) and ESR1(-) status relates to epigenetic changes in breast cancer-related genes and to correlate with molecular breast cancer subtypes. Methods: Since January/02 to June/05, we quantified methylation levels ERS1 gene in serum of 92 pts breast cancer. A PCR quantitative technique was used to analyze levels of methylation gene. We also examined and correlationed the expression of ESR1 in tumors by immunohistochemistry with molecular phenotype. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement (N0; 63%, N1; 30%, N2; 7%), tumor size (T1; 58%, T2; 35%, T3; 4%, T4; 4%) and grade (G1; 20%, G2; 37%, G3; 30%). Of the cases, 37 pts (40%) were Luminal A (LA), 32 pts (33%) Luminal B (LB), 14 pts (15%) Triple-negative (TN) and 9pts (10%) HER2+. The methylated ESR1 in serum was significantly associated with ESR1(-) in breast tumors >80% (p=0.0179). Methylation ESR1 was preferably associated with TN (80%) and HER2+ (60%) subtype. Nevertheless unmethylation ESR1 was found more frequently in LA (71%) and LB (59%) phenotype. With a median follow up of 5 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene (p>0.05), Luminal A; ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B; ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative; ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2; ESR1 Methylation SG at 5 years was 66.7% vs 75% unmethylation ESR1. Conclusions: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Our study identifies the presence of variations in global levels of methylation promoters ESR1 genes in breast cancer with different phenotype classes and shows that these differences have clinical significance. Although numerous issues remain to be resolved, quantitative measurement of circulating methylated DNA may be of significance in the assessment and search of targeted therapy resistance related to ESR1 and HER2 status by epigenetic or transcriptional cancer therapy.

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Serum chemokine CXCL7 activity after resection of breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22182 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22182-e22182

Author(s):

Mary Ann Kosir ◽

Donghong Ju

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Serum Levels ◽

Partial Mastectomy ◽

Enzyme Linked Immunosorbent Assay ◽

Normal Donor ◽

Breast Cancer Patients ◽

Serum Samples ◽

Preoperative Serum ◽

Er Positive

e22182 Background: The chemokine CXCL7 is associated with tumor migration, invasion and angiogenesis and is a ligand for CXCR2. The purpose of the study is to measure changes in serum chemokine CXCL7 from resectable breast cancer patients between preoperative and postoperative blood samples. Methods: With IRB approval, we prospectively collected serum samples from patients undergoing breast cancer surgery immediately preoperatively and at least one week postoperatively. Serum CXCL7 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System (R and D Systems, Minneapolis, MN) according to manufacturer’s instructions. Measurements were performed in duplicate with three separate experiments. Results were analyzed using unpaired and paired Student’s t-Test. Demographic and clinical information were collected. Normal donor samples were from ProteoGenex. Results: Twenty-three matched serum samples were analyzed. The mean age was 52 years (range 36-67), 65.2% were African American, 56.5% underwent partial mastectomy. There were 5 in Stage I, 9 in Stage II, 2 in Stage III, and 7 in Stage 0. Only 4 of 16 with invasive cancer had nodal disease, 11 were ER positive, 6 were triple negative, and 5 of 7 with DCIS were ER positive. Matched serum samples showed greater CXCL7 serum levels in preoperative samples when compared to normal donor samples (9.10 ±0.45 vs 8.10 ± 0.22 ug/ml; mean±sem, p<0.05). The CXCL7 serum levels were significantly decreased in postoperative serum as compared to preoperative serum (8.40 ± 0.47 vs 9.10 ± 0.45 ug/ml; mean±sem, p<0.05) reaching normal donor serum levels. When individual matched pairs of serum were analyzed, 16 showed decrease in postoperative CXCL7 levels compared to preoperative. Conclusions: The chemokine CXCL7 found in serum is increased in breast cancer patients compared to normal donors, and significantly decreases postoperatively to normal levels. This supports translational research of the role of CXCL7 in breast cancer.

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Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

Journal of Clinical Oncology ◽

10.1200/jco.2011.38.8595 ◽

2012 ◽

Vol 30 (15) ◽

pp. 1796-1804 ◽

Cited By ~ 1161

Author(s):

Gunter von Minckwitz ◽

Michael Untch ◽

Jens-Uwe Blohmer ◽

Serban D. Costa ◽

Holger Eidtmann ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Pathologic Complete Response ◽

Complete Response ◽

Invasive Disease ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes ◽

Luminal B

Purpose The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Methods Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane–based chemotherapy in seven randomized trials were analyzed. Results Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) –negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis. Conclusion pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

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