Obesity at diagnosis and breast cancer (BC) recurrence risk based on the 21-gene assay recurrence score (RS).

555 Background: Obesity at diagnosis has been associated with poorer overall survival in BC patients. The Oncotype Dx 21-gene assay RS has been shown to predict the risk of distant recurrence in estrogen receptor (ER) positive BC. This study aimed to evaluate if an association exists between body mass index (BMI) and RS. Methods: Retrospective chart review of patients (pts) with BC diagnosed 2005-2010 and a 21-gene assay was performed. Risk factors including BMI, hormone use, and menopausal status were collected as well as tumor characteristics such as ER/PR/HER2 status, stage, and grade. Univariate analysis of the association between BMI level (<30 vs ≥30), and RS (≤18 vs >18), stage (I vs II), and grade (1 vs 2 vs 3) was conducted using Chi square test. Correlation of BMI with RS (0-100) was also assessed via Spearman’s correlation. All tests were at a two sided significance level of 0.05. Results: Of 495 pts with a RS value, 482 had a BMI within 6 months of diagnosis. Median BMI was 27.7 kg/m2 (range 17-63). BMI for pts presenting with stage 2 disease is significantly higher (30±6.9) than those with stage 1 (29±7.8), p=0.04 (Wilcoxon rank sum test). No association was found between BMI level and stage, grade or RS. See Table. Mean RS was 18.8 vs 18.2 (BMI <30 vs ≥30), p=0.79 (Wilcoxon rank sum test). Conclusions: This is the largest study of the association between BMI and the RS. Obesity (BMI≥30) has been associated with increased recurrence and death from BC. However, we found no association between BMI and RS. This suggests that poorer outcomes among obese ER+ breast cancer patients may not be due to intrinsic tumor biology (as reflected in the RS), but to other non-tumor factors, whether higher circulating estrogen levels, reduced efficacy of aromatase inhibitors, other comorbidities, difficulty with chemotherapy or other unidentified factors. Further study is warranted. [Table: see text]

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Rural versus urban differences among patients (pts) with hormone-receptor positive (HR+) breast cancer (BC) and a 21-gene assay recurrence score (RS).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6063 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6063-6063

Author(s):

Molly Andreason ◽

Chong Zhang ◽

Adedayo A. Onitilo ◽

John A. Charlson ◽

Wendy M. Ledesma ◽

...

Keyword(s):

Endocrine Therapy ◽

Univariate Analysis ◽

Tumor Biology ◽

Recurrence Score ◽

Retrospective Chart Review ◽

Recurrence Risk ◽

Chi Square ◽

Significance Level ◽

Prospective Comparison ◽

Gene Assay

6063 Background: Differences in BC outcomes have been noted between rural and urban women. The influence of tumor biology vs treatment factors as the driver of these differences remains unclear. The Oncotype Dx 21-gene assay RS predicts distant recurrence risk for HR+BC; a RS>18 indicates possible chemotherapy benefit. We assessed rural vs urban differences in RS and therapies received (endocrine therapy; chemotherapy for RS>18). Methods: Retrospective chart review was conducted on BC pts diagnosed 2005–2010 with a 21-gene assay RS. Stage, grade, medications and receptor status were abstracted; RS information was obtained from Genomic Health. Rural-Urban Commuting Area (RUCA) codes defined rural vs urban status. Comparisons between rural vs urban pts were made using two-sample tests, chi-square or Fisher’s exact test for discrete data such as RS (≤ 18 vs > 18), stage and ER status. T- or Wilcoxon rank sum test were used for continuous data (RS 0-100 and age.) All tests were at a two-sided significance level of 0.05. Results: Of 495pts with RS, 488 had RUCA codes (91% white, 61% postmenopausal). For rural vs urban pts, mean RS was 18 vs 19, p=0.15. The table shows univariate analysis for other predictors. For treatment, 321/354 (97%) rural vs 118/134 (94%) urban pts started endocrine therapy (p=0.2). For RS>18, 17/55 (31%) rural vs 83/165 (50%) urban pts received chemotherapy (p=0.02, Chi-square test). Conclusions: Rural pts did not have significantly different RS compared with urban pts, but received significantly less chemotherapy for RS>18. This suggests that for HR+ BC, rural vs urban discrepancies may be explained in part by treatment factors. We suggest prospective comparison or confirmation in another cohort. [Table: see text]

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10-year update of E2197: Phase III doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) adjuvant treatment of LN+ and high-risk LN- breast cancer and the comparison of the prognostic utility of the 21-gene recurrence score (RS) with clinicopathologic features.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1021 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1021-1021 ◽

Cited By ~ 4

Author(s):

Joseph A. Sparano ◽

Anne O'Neill ◽

Robert James Gray ◽

Edith A. Perez ◽

Lawrence N. Shulman ◽

...

Keyword(s):

Breast Cancer ◽

Menopausal Status ◽

Disease Free Survival ◽

Recurrence Score ◽

Phase Iii ◽

Clinicopathologic Characteristics ◽

Accurate Predictor ◽

Gene Assay ◽

Node Positive Disease

1021 Background: At 5 years, AT did not improve disease free survival or overall survival and RS was a more accurate predictor of relapse than standard clinicopathologic characteristics for patients with hormone receptor (HR) positive tumors. Methods: A Phase III Intergroup trial tested adjuvant AT vs. AC. Women with 1-3 N + or N - and T-size > 1cm were randomized to 4 cycles of AT (60 mg/m2/60 mg/ m2) or AC (60 mg/m2/600 mg/m2) q 3 wk x 4. Patients(pts) with ER + and/ or PR + tumors received tam for 5 yrs. Pts were stratified by nodal, HR (ER+ PR+, ER+PR-, ER-PR+, ER-PR-, ER/PR unk) and menopausal status. The primary endpoint was DFS. A sample of 465 pts with HR + breast cancer with 0 to 3 positive axillary nodes who did (N =116) or did not have a recurrence had tumor tissue evaluated using the 21- gene assay. Grade and HR expression were evaluated locally and centrally. Results: 2952 pts were randomized between 7/30/98 and 1/21/00. 2883 were eligible and analyzable. Arms were balanced for age, HR, menopause, nodes, surgery, grade and T-size: median age 51; 64% ER +; 65% LN-; grade: 10% low, 38% int., 46% high; and median T-size - 2.0 cm. At a median follow-up of 11.5 years the DFS/OS results are shown in the table below. RS was a highly significant predictor of recurrence including node negative and node positive disease (P < .0001) and predicted recurrence more accurately than clinical variables. Conclusions: At 11.5 yrs. median follow-up, there remains no difference in DFS or OS, although there continue to be fewer events in the AT arm in the prespecified ER/PR negative subgroup. At 10 years, the RS continues to be a more accurate predictor of relapse than standard clinical features. [Table: see text]

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Patient-reported cognitive impairments among women with breast cancer randomly assigned to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT): Results from the Trial Assigning Individualized Options for Treatment (TAILORx).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9020 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9020-9020

Author(s):

Lynne I. Wagner ◽

Robert James Gray ◽

George W. Sledge ◽

Timothy Joseph Whelan ◽

Daniel F. Hayes ◽

...

Keyword(s):

Breast Cancer ◽

Hormonal Therapy ◽

Cognitive Impairments ◽

Menopausal Status ◽

Recurrence Score ◽

Well Being ◽

Control Group ◽

Breast Cancer Patients ◽

Change Scores ◽

Patient Reported

9020 Background: Cognitive impairment is a complication of chemotherapy. Perceived cognitive impairments (PCI) were prospectively assessed among TAILORx participants randomized to HT alone versus chemotherapy followed by HT (C+HT). Methods: TAILORx participants with an OncoType DX Recurrence Score 11-25 were randomly assigned to HT or C+HT. PCI, fatigue, endocrine symptoms and health-related quality of life (HRQL) were assessed at baseline, 3, 6, 12, 24, and 36 months, using the Functional Assessment of Cancer Therapy (FACT) in 455 patients enrolled after 1/15/10. PCI change scores > 4.5 from baseline were defined a priori as clinically meaningful. Linear regression (LR) was used to model PCI scores on baseline PCI, treatment and other factors. Results: PCI scores were significantly worse at 3, 6, and 12 months compared to baseline for both groups (Table). The decline was greater for C+HT than HT at 3 months, but scores were similar at 12 months. Tests of an interaction between menopausal status and treatment were non-significant. PCI correlated with fatigue (r = 0.57-0.64) but not FACT Emotional well-being (EWB; r = 0.28-0.38); controlling for EWB did not account for differences in PCI change scores between treatment arms. Conclusions: Our study is the first to examine PCI among breast cancer patients randomized to receive C+HT vs. HT alone. C+HT was associated with greater declines in PCI at 3 months, but at 12 months PCI was similar in the C+HT and HT groups. PCI was associated with fatigue but not EWB. Pre- and post-menopausal groups demonstrated the same pattern of change. Since this study did not include a control group of patients not treated with HT, further study is required to determine if and to what extent HT contributes to PCI. [Table: see text]

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Factors associated with axillary conversion after neoadjuvant chemotherapy in initially node positive breast cancer patients: A transSENTINA analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.567 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 567-567

Author(s):

Hans-Christian Kolberg ◽

Thorsten Kühn ◽

Maja Krajewska ◽

Ingo Bauerfeind ◽

Tanja N. Fehm ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Lymph Nodes ◽

Primary Tumor ◽

Tumor Biology ◽

Her2 Status ◽

Tumor Diameter ◽

Breast Cancer Patients ◽

Axillary Surgery ◽

Small Patient Number

567 Background: Current study concepts in early breast cancer after neoadjuvant chemotherapy (NAT) are aiming at reducing morbidity by omission of axillary surgery in selected patients. Selection criteria for this strategy have to include the probability of conversion from cN1 to ycN0. We analyzed the association of clinical/pathological parameters and axillary conversion with data from arms C and D of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were recruited to Arms C/D of the SENTINA trial in case they presented with clinically positive nodes before NAT. Based on their response to NAT they were then assigned to either arm C (clinically conversion to ycN0) or arm D (no clinical conversion (ycN+). In both the pre- and post-NAT scenarios, clinically involved lymph nodes were defined as palpable and/or suspect by ultrasound. Univariate logistic regression analyses were carried out to evaluate the association between clinical/pathological parameters and axillary conversion after NAT. Results: Of the 892 patients in arms C and D of the SENTINA trial 716 were evaluable for this analysis. After NAT, 593 patients converted to ycN0 and were therefore assigned to arm C; in contrast, 123 patients still had involved lymph nodes after NAT (ycN+) and were assigned to Arm D. Arms C and D were compared regarding the clinical/pathological parameters tumor diameter by ultrasound before and after NAT, grading, multifocality, ER status, PR status, HER2 status, pathological complete remission in the breast (breast pCR), morphology, lymphovascular invasion (LVI) and hemangiosis. Only small tumor diameter after NAT (p = 0.0038), achievement of breast pCR (p = 0.0001) and lack of LVI (p = 0.0009) were positively associated with axillary conversion from cN1 to ycN0 after NAT. Conclusions: Because of the small patient number in arm D, we were not able to identify an association between parameters of tumor biology (ER, PR, HER2 and TN status) and axillary conversion. However, favorable response of the primary tumor (represented both clinically by tumor diameter after NAT and pathologically by pCR in the breast) were positively associated with conversion from cN1 to ycN0. These results justify including patients with clinical and pathological response of the primary tumor in trials investigating de-escalation of axillary surgery after NAT.

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Outcome of Patients With Early-Stage Breast Cancer Treated With Doxorubicin-Based Adjuvant Chemotherapy As a Function ofHER2andTOP2AStatus

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.1566 ◽

2009 ◽

Vol 27 (24) ◽

pp. 3881-3886 ◽

Cited By ~ 52

Author(s):

Raymond Tubbs ◽

William E. Barlow ◽

G. Thomas Budd ◽

Eric Swain ◽

Peggy Porter ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Early Stage ◽

Univariate Analysis ◽

Menopausal Status ◽

Disease Free Survival ◽

Early Stage Breast Cancer ◽

Breast Cancer Patients ◽

Her2 Amplification ◽

Amplification Ratio

PurposeAmplification and deletion of the TOP2A gene have been reported as positive predictive markers of response to anthracycline-based therapy. We determined the status of the HER2 and TOP2A genes in a large cohort of breast cancer patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C).Patients and MethodsTOP2A/CEP17 and HER2/CEP17 fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) constructed from 2,123 of the 3,125 women with moderate-risk primary breast cancer who received equivalent doses of either concurrent adjuvant chemotherapy with A plus C (n = 1,592) or sequential A followed by C (n = 1,533).ResultsAn abnormal TOP2A genotype was identified for 153 (9.4%) of 1,626 patients (4.0% amplified; 5.4% deleted). An abnormal HER2 genotype was identified for 303 (20.4%) of 1,483 patients (18.8% amplified; 1.6% deleted). No significant differences in either overall survival (OS) or disease-free survival (DFS) were identified for TOP2A. In univariate analysis, OS and DFS rates were strongly and adversely associated only with higher levels of HER2 amplification (ratio ≥ 4.0). Survival was not associated with low-level HER2 amplification (ratio ≥ 2; OS hazard ratio [HR], 1.14; P = .39; DFS HR, 1.07; P = .62), but it was associated for a ratio ≥ 4 (OS HR, 1.45; P = .03; DFS HR, 1.38; P = .033), in which analysis was adjusted for menopausal status, hormone receptor status, treatment, number of positive nodes, and tumor size.ConclusionIn this population of patients with early-stage breast cancer who were treated with adjuvant AC chemotherapy, TOP2A abnormalities were not associated with outcome. HER2 high-level amplification was a prognostic marker in anthracycline-treated patients.

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Linc00665 Can Predict the Response to Cisplatin-Paclitaxel Neoadjuvant Chemotherapy for Breast Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.604319 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huijuan Dai ◽

Xiaonan Sheng ◽

Rui Sha ◽

Jing Peng ◽

Fan Yang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Univariate Analysis ◽

Enrichment Analysis ◽

Predictive Biomarker ◽

Gene Set Enrichment Analysis ◽

Her2 Status ◽

Breast Cancer Patients ◽

Kegg Analysis

ObjectiveLinc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.Materials and MethodsThe present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.ResultsThe present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125–0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104–0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.ConclusionLinc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.

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Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.619840 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yiwei Tong ◽

Weiqi Gao ◽

Jiayi Wu ◽

Siji Zhu ◽

Ou Huang ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Prognostic Value ◽

Single Gene ◽

Menopausal Status ◽

Recurrence Score ◽

Risk Category ◽

Obese Patients ◽

Breast Cancer Patients

PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

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Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1561 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1561-1561

Author(s):

Sangeetha Meda Reddy ◽

Maureen Sadim ◽

Irene B. Helenowski ◽

Jun Li ◽

Nengjun Yi ◽

...

Keyword(s):

Breast Cancer ◽

Weight Gain ◽

Cancer Patients ◽

Menopausal Status ◽

High Risk Patient ◽

Cancer Recurrence ◽

Her2 Status ◽

Breast Cancer Patients ◽

Mortality And Morbidity ◽

Response To Chemotherapy

1561 Background: Obesity and weight gain in breast cancer patients has been associated with decreased quality of life, decreased response to chemotherapy, increased cancer recurrence, and higher all-cause mortality. Our study was designed to identify factors that contribute to this weight gain. Methods: Chart review was conducted on 565 breast cancer patients to obtain weights and BMIs over an 18 month period from diagnosis, tumor characteristics (ER/PR/Her2 status, grade, presence of LN metastases, stage), demographics (age, race), clinical factors (menopausal status), and treatment regimens (chemotherapy, hormone therapy, radiation). Blood samples were genotyped for polymorphisms in FTO (fat mass and obesity-associated protein) and the adiponectin pathway, two pathways found to be associated with obesity and breast cancer risk. Results: See table. For genetic analysis, one statistically significant epistatic and three gene x environmental interactions were detected for adiponectin SNPs: rs822396d x BMI at diagnosis (effect size 8.65), rs2232853a x age (2.75), rs1501299a x BMI at diagnosis (3.63), and rs266729d x rs7539542d (6.40). Conclusions: We have identified multiple clinical and genetic variables that are likely predictors of weight gain in breast cancer patients. We are conducting a prospective study of 200 breast cancer patients to validate the findings of this retrospective study. By identifying a high risk patient population, we hope to target them for aggressive lifestyle interventions to prevent weight gain and thereby improve their mortality and morbidity. [Table: see text]

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Comparison between the american joint committee on cancer (ajcc) anatomic and prognostic stages for breast cancer

Mastology ◽

10.29289/259453942020v30s1057 ◽

2020 ◽

Vol 30 (Suppl 1) ◽

Author(s):

Mariana Soares Cardoso ◽

Marcelo Antonini Matheus de Paula Solino

Keyword(s):

Breast Cancer ◽

Surgical Treatment ◽

Hormone Receptors ◽

Histological Grade ◽

Menopausal Status ◽

Recurrence Score ◽

Clinical Staging ◽

Molecular Profile ◽

Breast Cancer Patients ◽

Genomic Test

Introduction: The knowledge regarding the biology of breast cancer has grown substantially and resulted in the identification of different breast cancer subtypes based on their molecular profile, which led to an important change in treatment, from a standardized therapy to a personalized one. A panel of experts and AJCC representatives were responsible for preparing the most recent Cancer Staging Manual. The panel recognized the clinical usefulness of biological factors such as histological grade, expression of hormone receptors (HR; estrogen and progesterone) and overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2) in predicting patient survival7 and incorporated data regarding these biomarkers in the new staging system. In addition, for eligible cases, the ‘Recurrence score’ was also incorporated, generated by the analysis of OncotypeDx (genomic test). The new manual, therefore, started to use 3 stagings. Anatomical staging – based on the classic TNM; clinical prognostic staging and pathological prognosis – association of TNM with prognostic biomarkers (using clinical data in the first and data after surgical treatment in the second). Objective: To verify the agreement between anatomical staging from the 7th edition of the AJCC manual and the prognosis from its 8th edition in a cohort of breast cancer patients at the Hospital do Servidor Público Estadual de São Paulo. Methodology: Observational and cross-sectional study, which evaluated patients undergoing surgical treatment at Hospital do Servidor Público Estadual from March, 2014 to March, 2019. Information was collected regarding age, menopausal status, tumor characteristics, anatomical and clinical staging, neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy, and type of surgery performed. Patients were staged using the digital platform “TNM8 Breast Cancer Calculator”. Results: 805 patients were included in the analysis. All patients were females aged between 29 and 97 years, mostly in the post-menopausal period (78.88%). 74.04% of cases were positive for ER, 66.21% PR-positive, and 88.07% HER2-negative. Prognostic staging downgraded a total of 285 out of 805 patients (35.4%). Almost all of the cases that decreased in staging were ER and/or PR+ (283 of 285). Most of those who went up were Triple Negatives (100 out of 111). Conclusion: Prognostic Staging changes the staging in almost half of the cases and there was a greater number of decreased staging in total and an association of increased staging with tumors considered to have a worse prognosis, which is in agreement with several studies already carried out since the new manual came out.

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Clinical Significance and Genetic Characteristics in HER2 Low Expression Tumors of Hormone Receptor Positive Breast Cancer Patients

10.21203/rs.3.rs-752911/v1 ◽

2021 ◽

Author(s):

Mengdi Chen ◽

Deyue Liu ◽

Weilin Chen ◽

Weiguo Chen ◽

Kunwei Shen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Hormone Receptor ◽

Disease Free Survival ◽

Recurrence Score ◽

Breast Cancer Patients ◽

Genetic Characteristics ◽

Significant Difference ◽

Gene Assay ◽

Low Expression

Abstract BackgroundHuman epidermal growth factor receptor 2 (HER2) low expressed breast cancer was considered as a distinct subtype different from HER2 negative tumors. We investigated the clinicopathological features and recurrence score (RS) of HER2-low and HER2- patients and their prognostic value in hormone receptor (HR) positive breast cancer.MethodsA total of 2,099 HR-positive primary female breast cancer patients between Jan 2009 and Jan 2019 were collected and tumors with immunohistochemistry 1 + or 2 + with negative in situ hybridization results was defined as HER2 low. We retrospectively compared the clinical and genetical features of HER2-low (n = 1,732) and HER2- (n = 367) breast cancer and theirs impacts on disease-free survival (DFS).ResultsThe HER2 low tumors had a higher ratio of concurrent estrogen receptor (ER) high expression than HER2- patients both at protein level (ER > 90%: 78.2% vs 58.6%, p < 0.01) and mRNA level (Spearman R = 0.5 vs 0.3). Analysis about DFS showed no significant difference between HER2 negative and low subgroups (5-year DFS: 92.3% vs 93.3%, p = 0.83). However, RS range (cut-off: 18 and 30) didn’t maintain its predictive value in HER2 low patients (p = 0.11) unlike that in HER2- group (p = 0.003). Further research for respective gene suggested that proliferation related genes performed well in predicting DFS in HER2- patients but lost its value in HER2 low group (p for interaction < 0.01). Contrarily, higher HER2 module was associated with worse DFS only in HER2 low patients (p = 0.04).ConclusionOur study found that HER2 low expression couldn’t be a prognostic factor in HR + patients. HER2-low patients had a higher proportion of ER high expressed tumors than HER2- ones did. The 21-gene assay and its proliferation module might be less applicable to HER2-low patients compared with HER2- patients.

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