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

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.

Outcome Evaluation in Pre-Trastuzumab Era between Different Breast Cancer Phenotypes: A Population-Based Study on Italian Women

2012 ◽  
Vol 98 (6) ◽  
pp. 743-750 ◽  
Author(s):  
Laura Cortesi ◽  
Elisabetta De Matteis ◽  
Claudia Cirilli ◽  
Luigi Marcheselli ◽  
Manuela Proietto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B ◽  
Italian Women ◽  
Disease Free ◽  
Over Time

Aims and background Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2–, Ki67 <14%), luminal B (ER and/or PgR/HER2–, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2–), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women. Methods and study design We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated. Results A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups. Conclusions In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.

Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11516-e11516
Author(s):  
A. Guerrero-Zotano ◽  
J. Gavila ◽  
M. A. Climent ◽  
M. J. Juan ◽  
V. Guillem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Breast Cancer Subtypes ◽  
Nuclear Staining ◽  
Luminal A ◽  
Long Term Outcome ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.

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

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.

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

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.

Subsequent pregnancy and long-term safety from breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13575-e13575
Author(s):  
Yunyeong Kim ◽  
Minsun Kang ◽  
Jaehun Jung ◽  
Eun Kyung Cho ◽  
Heung Kyu Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Tumor Subtypes ◽  
Study Population ◽  
Disease Free

e13575 Background: Long-term safety of pregnancy after breast cancer still remained controversial, especially according to tumor subtypes. Prior results of other studies have limitations of short follow-up periods or small groups. Methods: We analyzed a population-based retrospective cohort data extracted from a random sample of 50% of women aged between 20 and 60 years who were diagnosed with breast cancer from 2002 to 2017 in the Korean National Health Insurance Service database. Propensity score matching analysis for age and Charlson Comorbidity Index (CCI) variables was performed for pregnant groups and non-pregnant groups with the same type of hormone therapy, chemotherapy and surgery. Study population was categorized to 4 biologic subgroups by the combination of hormone therapy, chemotherapy and target therapy. In this observational study, 1,566 patients with pregnancy after breast cancer were matched (1:2) to 2,462 non-pregnant patients of similar characteristics, adjusting for guaranteed bias. The matched patients were followed up to 7 years, or disease and mortality occurrence after the diagnosis of breast cancer. Survival estimates were calculated using the Kaplan-Meier analysis, groups were compared with the log-rank test. Results: Mean time from diagnosis to pregnancy was 3.4 years in study population. At a follow-up of 7 years after pregnancy, no inferiority in disease-free survival and overall survival was observed in pregnant patients factoring in treatment bias. In sub-analysis according to tumor subtypes, no difference in disease-free survival was observed between pregnant and non-pregnant patients in HR-positive and triple negative subgroup ( p= 0.088, p= 0.048, respectively). Likewise, no overall survival difference was observed in ER-positive patients and triple negative patients ( p= 0.05∼0.73, p= 0.03∼0.09, respectively). Conclusions: Our observational data provides reassuring evidence on long-term safety of pregnancy in young breast cancer patients, regardless of tumor subtypes.

scholarly journals Comprehensive profiling of liver x receptor splicing in triple negative breast cancer reveals existence of novel splice variants that are prognostic for survival

2021 ◽  
Author(s):  
Priscilia Lianto ◽  
J Bernadette Moore ◽  
Thomas A Hughes ◽  
James L Thorne
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Splice Variants ◽  
Disease Free Survival ◽  
Full Length ◽  
High Expression ◽  
Free Survival ◽  
Cancer Subtypes ◽  
Disease Free

The liver x receptors (LXR) alpha and beta are ligand-responsive transcription factors that link homeostatic control of lipid metabolism with cancer pathophysiology and prognosis. LXR activity is elevated in triple negative breast cancer relative to other breast cancer subtypes, driving gene signatures associated with drug resistance and metastasis. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Seven splice variants of LXRα or LXRβ were detected. Three have not been recorded previously and five were prognostic. High expression of full length LXRα was associated with shorter disease-free survival but splice variants harbouring truncations of the ligand binding domain were prognostic for improved survival. All LXRa variants were associated with longer disease-free survival. Mechanistically, while full length LXRα positively correlated with target gene expression in primary samples, LXRβ was inversely correlated. We conclude that canonical LXRα function is an oncogenic driver of triple negative tumour pathophysiology that can be countered by high expression of truncated splice variants and/or full length LXRβ.

scholarly journals Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1304 ◽  
Author(s):  
Nancy Y. Yu ◽  
Adina Iftimi ◽  
Christina Yau ◽  
Nicholas P. Tobin ◽  
Laura van ’t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Recurrence ◽  
Tamoxifen Therapy ◽  
Recurrence Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B

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

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.

BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Bryan P. Schneider ◽  
Guanglong Jiang ◽  
Tarah J. Ballinger ◽  
Fei Shen ◽  
Christopher Chitambar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free ◽  
Versus Treatment ◽  
Tumor Dna

PURPOSE Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.

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