scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

scholarly journals Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

2019 ◽  
Vol 7 (21) ◽  
pp. 3534-3539
Author(s):  
Nada A. S. Alwan ◽  
Furat N. Tawfeeq
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

scholarly journals VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

2014 ◽  
Vol 21 (4) ◽  
pp. 587-599 ◽  
Author(s):  
María Ángeles Castilla ◽  
María Ángeles López-García ◽  
María Reina Atienza ◽  
Juan Manuel Rosa-Rosa ◽  
Juan Díaz-Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Tissue Microarrays ◽  
The Cancer Genome Atlas ◽  
Luminal Progenitor ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Grade 3

Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a transcriptional co-activator structurally homologous toTAZandYAPthat modulates the Hippo pathway inDrosophila. In this study, we examined the expression ofVGLL1and its intronic miRNA, miR-934, in breast cancer.VGLL1and miR-934 expression miRNA profiling was carried out on frozen samples of grade 3 invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic andBRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to confirm differences inVGLL1and miR-934 expression in different breast cancer subtypes, and to correlate their expression with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR-934 was most strongly upregulated in ER-negative carcinomas, and its expression was correlated with that ofVGLL1. NuclearVGLL1expression was observed in 13% of sporadic breast carcinomas, and whileVGLL1was only occasionally found in luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2-positive (17%), triple-negative (TN) breast carcinomas (>40%) andBRCA1-associated TN carcinomas (>50%). These findings were confirmed in the TCGA dataset, which revealed positive associations with luminal progenitor genes (GABRP,SLC6A14,FOXC1,PROM1, andBBOX1) and strong negative correlations with ER-associated genes (ESR1,C6ORF211,GATA3, andFOXA1). Moreover,VGLL1expression was associated with reduced overall survival. In conclusion,VGLL1and miR-934 are mainly expressed in sporadic andBRCA1-associated TN basal-like breast carcinomas, and their coordinated expression, at least partially mediated by the direct modulation ofESR1, might be involved in the maintenance of a luminal progenitor phenotype.

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.

Q-CROC-03: A prospective biopsy driven clinical trial to study the mechanisms of resistance to chemotherapy in triple-negative breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1139-TPS1139
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Carole Seguin ◽  
Catalin Liviu Dragos Mihalcioiu ◽  
Josee-Anne Roy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Limiting Factors ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Tumor Resistance ◽  
Cancer Subtypes ◽  
Resistance To Chemotherapy

TPS1139 Background: Resistance to chemotherapy or targeted agents is the cause of death in most patients dying of breast cancer and one of the major challenges presently faced by oncologists. In triple negative breast cancers (TNBCs), drug resistance emerges quicker than in other breast cancer subtypes and contributes to the poor prognosis seen in these patients. The lack of targeted therapies to treat TNBC highlights the important need to better understand the molecular mechanisms contributing to chemotherapy resistance in order to develop new therapeutic strategies. However, the difficulty in obtaining tissue samples from drug resistant tumors has been one of the limiting factors in this field of study. Methods: We have designed a prospective phase II clinical trial where paired biopsies are collected from chemotherapy resistant TNBCs (NCT01276899). Four needle core biopsies are collected before the initiation of treatment and 2 weeks before surgery or at the time of progression in the neoadjuvant and metastatic settings respectively. Metastatic sites eligible for biopsy include liver, lung, skin and lymph nodes. This study is presently recruiting at 5 major health centers in Quebec and will soon open in the USA. We have currently enrolled 13 patients in the neoadjuvant setting and 2 metastatic patients. Major challenges in patient enrolment will be discussed. We have standardized the methods of collection and processing of tissue and blood specimens to ensure their molecular integrity and compatibility with different genomic and proteomic molecular platforms. Analysis of tumor cellularity has been incorporated into our quality control and we have optimized the extraction of nucleic acids to obtain high yields and optimal quality. Paired biopsies will undergo Next Gen Sequencing, flow sorted aCGH analysis, gene expression and miRNA profiling as well as phosphoproteomic profiling using reverse phase protein arrays. Collection of clinical data will allow molecular profiling data to be linked to clinical response data so as to determine DNA, RNA and protein factors correlated with tumor resistance to chemotherapy.

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

2012 ◽  
Vol 30 (15) ◽  
pp. 1796-1804 ◽  
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.

scholarly journals Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Ciara Duffy ◽  
Anabel Sorolla ◽  
Edina Wang ◽  
Emily Golden ◽  
Eleanor Woodward ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Membrane ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Treatment Strategies ◽  
Receptor Activation ◽  
Breast Cancers ◽  
Honeybee Venom ◽  
Cancer Subtypes

Abstract Despite decades of study, the molecular mechanisms and selectivity of the biomolecular components of honeybee (Apis mellifera) venom as anticancer agents remain largely unknown. Here, we demonstrate that honeybee venom and its major component melittin potently induce cell death, particularly in the aggressive triple-negative and HER2-enriched breast cancer subtypes. Honeybee venom and melittin suppress the activation of EGFR and HER2 by interfering with the phosphorylation of these receptors in the plasma membrane of breast carcinoma cells. Mutational studies reveal that a positively charged C-terminal melittin sequence mediates plasma membrane interaction and anticancer activity. Engineering of an RGD motif further enhances targeting of melittin to malignant cells with minimal toxicity to normal cells. Lastly, administration of melittin enhances the effect of docetaxel in suppressing breast tumor growth in an allograft model. Our work unveils a molecular mechanism underpinning the anticancer selectivity of melittin, and outlines treatment strategies to target aggressive breast cancers.

scholarly journals Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4137
Author(s):  
Sarah Bryan ◽  
Isabell Witzel ◽  
Kerstin Borgmann ◽  
Leticia Oliveira-Ferrer
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Future Research ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis

Breast cancer (BC) is the most frequent cause of cancer-associated death for women worldwide, with deaths commonly resulting from metastatic spread to distant organs. Approximately 30% of metastatic BC patients develop brain metastases (BM), a currently incurable diagnosis. The influence of BC molecular subtype and gene expression on breast cancer brain metastasis (BCBM) development and patient prognosis is undeniable and is, therefore, an important focus point in the attempt to combat the disease. The HER2-positive and triple-negative molecular subtypes are associated with an increased risk of developing BCBM. Several genetic and molecular mechanisms linked to HER2-positive and triple-negative BC breast cancers appear to influence BCBM formation on several levels, including increased development of circulating tumor cells (CTCs), enhanced epithelial-mesenchymal transition (EMT), and migration of primary BC cells to the brain and/or through superior local invasiveness aided by cancer stem-like cells (CSCs). These specific BC characteristics, together with the ensuing developments at a clinical level, are presented in this review article, drawing a connection between research findings and related therapeutic strategies aimed at preventing BCBM formation and/or progression. Furthermore, we briefly address the critical limitations in our current understanding of this complex topic, highlighting potential focal points for future research.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

scholarly journals Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2966-2973 ◽  
Author(s):  
Marco Colleoni ◽  
Bernard F. Cole ◽  
Giuseppe Viale ◽  
Meredith M. Regan ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Triple Negative ◽  
Alkylating Agents ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Tumor Subtypes ◽  
Node Negative Breast Cancer

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

Trends in breast cancer mortality according to molecular subtypes: A population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola
Keyword(s):  
Breast Cancer ◽  
Cancer Mortality ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Mortality ◽  
Treatment Strategies ◽  
Luminal A ◽  
Her2 Positive ◽  
Mortality Trends ◽  
Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

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