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

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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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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Magnetic resonance imaging (MRI) evaluation of pathologic complete response (pCR) in different breast cancer subtypes after neoadjuvant chemotherapy (NAC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1111 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1111-1111 ◽

Cited By ~ 1

Author(s):

Lucia Gonzalez-Cortijo ◽

Javier Hornedo ◽

Ricardo Sainz de la Cuesta ◽

Gines Hernandez-Cortes ◽

Ramon Perez-Carrion ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Residual Disease ◽

Residual Tumor ◽

Complete Response ◽

Late Enhancement ◽

Her2 Positive ◽

Cancer Subtypes ◽

Er Positive

1111 Background: MRI is being used to address treatment response to NAC in breast cancer patients. However, its ability to predict pCR in histologically different tumors remains unclear. We tried to investigate the usefulness of MRI in evaluation of pCR in different breast cancer subtypes after treatment with NAC. Methods: Serial MRI studies were acquired before, during and after NAC in 75 evaluable patients. MRI interpretation included lesion size, morphology and dynamic enhanced evaluation imaging with initial and late enhancement. On the basis of the final MRI, response was determined to be a clinically complete response (CCR) when no residual tumor and no late enhancement were found. By using inmunohistochemistry and fluorescence in situ hybridization (FISH) for human epidermal growth factor receptor 2 (HER2/neu) amplification, tumors were divided into three subtypes: triple negative, HER2 positive, and estrogen receptor (ER) positive/HER2 negative. Every patient received chemotherapy with taxanes and anthracyclines and HER2 positive tumors were treated with trastuzumab. All patients received surgery. pCR was defined as no residual invasive tumor in the surgical specimen. Ductal carcinoma in situ residual disease was considered pCR. Results: 22 of 75 patients (29%) achieved a CCR on the final MRI. Of 22 patients with CCR all 22 (100%) were confirmed pathologically. 19 were pathologic complete responses and 3 showed in situ microscopic residual disease. 12 (55%) were HER2 positive tumors, 4 (18%) were triple negative tumors and 6 (27%) were ER positive/HER2 negative tumors. The negative predictive value of MRI for predicting pCR after NAC was 100%. Conclusions: Absence of both residual tumor and late enhancement in MRI predict pCR with high accuracy in triple negative, HER2 positive and ER positive/HER2 negative breast cancer after NAC.

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

Tumori Journal ◽

10.1177/03008916211012341 ◽

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.

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Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy

Oncotarget ◽

10.18632/oncotarget.25413 ◽

2018 ◽

Vol 9 (41) ◽

pp. 26406-26416 ◽

Cited By ~ 36

Author(s):

Angela Santonja ◽

Alfonso Sánchez-Muñoz ◽

Ana Lluch ◽

Maria Rosario Chica-Parrado ◽

Joan Albanell ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Response Rate ◽

Complete Response Rate ◽

Pathologic Complete Response ◽

Complete Response ◽

Cancer Subtypes ◽

Pathologic Complete Response Rate

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.572 ◽

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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Neoadjuvant Pertuzumab plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2 Positive Breast Cancer: Real-World Data from a National Institute of Oncology in Poland.

10.20944/preprints202201.0164.v1 ◽

2022 ◽

Author(s):

Agnieszka Irena Jagiełło-Gruszfeld ◽

Magdalena Rosinska ◽

Malgorzata Meluch ◽

Katarzyna Pogoda ◽

Anna Niwińska ◽

...

Keyword(s):

Breast Cancer ◽

Pathologic Complete Response ◽

Complete Response ◽

Her2 Positive ◽

Real World Data ◽

Cancer Subtypes ◽

Cancer Management ◽

Her2 Positive Breast Cancer ◽

Neoadjuvant Systemic Therapy ◽

Positive Breast Cancer

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

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Analysis of prolactin receptor expression in breast cancer subtypes

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20206601089 ◽

2020 ◽

Vol 66 (1) ◽

pp. 89-94

Author(s):

T.S. Kalinina ◽

V.V. Kononchuk ◽

S.V. Sidorov ◽

L.F. Gulyaeva

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Prolactin Receptor ◽

Mrna Level ◽

Receptor Expression ◽

Mrna Levels ◽

Luminal A ◽

Her2 Positive ◽

Tissue Samples ◽

Luminal B

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.

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

BioMed Research International ◽

10.1155/2020/8970340 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 3

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.

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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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