Evolution of low HER2 expression between early and advanced-stage breast cancer

AbstractNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

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Breast cancer treatment and survival differences in women in remote and socioeconomically disadvantaged areas, as demonstrated by linked data from New South Wales (NSW), Australia

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06170-2 ◽

2021 ◽

Author(s):

Elizabeth Buckley ◽

Elisabeth Elder ◽

Sarah McGill ◽

Zahra Shahabi Kargar ◽

Ming Li ◽

...

Keyword(s):

Breast Cancer ◽

Socioeconomic Status ◽

Breast Reconstruction ◽

Cancer Treatment ◽

Linked Data ◽

Breast Cancer Treatment ◽

Competing Risk ◽

Advanced Stage ◽

Lower Socioeconomic ◽

Cancer Plan

Abstract Introduction Reducing variations in cancer treatment and survival is a key aim of the NSW Cancer Plan. Variations in breast cancer treatment and survival in NSW by remoteness and socioeconomic status of residence were investigated to determine benchmarks. Reducing variations in cancer treatment and survival is a key aim of the NSW Cancer Plan. Variations in breast cancer treatment and survival in NSW by remoteness and socioeconomic status of residence were investigated to determine benchmarks. Methods A retrospective cohort study used linked data for invasive breast cancers, diagnosed in May 2002 to December 2015 from the NSW Cancer Registry, with corresponding inpatient, and medical and pharmaceutical insurance data. Associations between treatment modalities, area socioeconomic status and residential remoteness were explored using logistic regression. Predictors of breast cancer survival were investigated using Kaplan–Meier product-limit estimates and multivariate competing risk regression. Results Results indicated a high 5-year disease-specific survival in NSW of 90%. Crude survival was equivalent by residential remoteness and marginally lower in lower socioeconomic areas. Competing risk regression showed equivalent outcomes by area socioeconomic status, except for the least disadvantaged quintile, which showed a higher survival. Higher sub-hazard ratios for death occurred for women with breast cancer aged 70 + years, and more advanced stage. Adjusted analyses indicated more advanced stage in lower socioeconomic areas, with less breast reconstruction and radiotherapy, and marginally less hormone therapy for women from these areas. Conversely, among these women who had breast conserving surgery, there was higher use of chemotherapy. Remoteness of residence was associated in adjusted analyses with less radiotherapy and less immediate breast reconstruction. In these short term data, remoteness of residence was not associated with lower survival. Conclusion This study provides benchmarks for monitoring future variations in treatment and survival.

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Communication and planning at the end-of-life: A survey of women with advanced stage breast cancer

Journal of Communications In Healthcare ◽

10.1179/cih.2009.2.4.371 ◽

2009 ◽

Vol 2 (4) ◽

pp. 371-386 ◽

Cited By ~ 5

Author(s):

Susan Bauer-Wu ◽

Katherine Yeager ◽

Rebecca L. Norris ◽

Qin Liu ◽

Karleen R. Habin ◽

...

Keyword(s):

Breast Cancer ◽

End Of Life ◽

Advanced Stage

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Pattern of Presentation of Mammography in a Developing Country

Nepalese Journal of Radiology ◽

10.3126/njr.v10i2.35974 ◽

2020 ◽

Vol 10 (2) ◽

pp. 33-37

Author(s):

Birendra Raj Joshi

Keyword(s):

Breast Cancer ◽

Developing Country ◽

Tertiary Hospital ◽

Dense Breast ◽

Advanced Stage ◽

Cancer Death ◽

Convenience Sampling

Introduction: Breast cancer is the second commonest cancer (7.2%) in Nepal and almost 54%of patients present in the advanced stage. It is the leading cause of cancer death in females.The objective of the study was to determine the type of mammography, composition of breastdensity and BIRADS category.Methods: The study was conducted in a tertiary hospital from Jan 1st to Oct 30th of 2019according to non-probability convenience sampling. A total of 388 persons were included inthe study. The mammographic findings were assessed by categories based on the BIRADSsystem.Results: Mammography for screening was 38 percent and diagnostic was 68 percent. Commonbreast compositions were B and C. More frequent BIRADS categories were seen in 1 and 2.Conclusion: Dense breast is common in mammography. BIRADS categories 1 and 2 weremore common than other categories.

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Abstract PD6-09: Herpet study- PET imaging of HER2 expression in breast cancer using the novel Affibody tracer [18F]GE-226, a first in patient study

10.1158/1538-7445.sabcs20-pd6-09 ◽

2021 ◽

Author(s):

Laura M. Kenny ◽

Gosala S. Gopalakrishnan ◽

Tara D. Barwick ◽

Vijay Vaja ◽

S. Hope McDevitt ◽

...

Keyword(s):

Breast Cancer ◽

Pet Imaging ◽

The Novel ◽

Her2 Expression ◽

Patient Study

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Long-Term Survival Outcomes of Patients with Small (≤ 1 Centimetre) Node-Negative HER2-Positive Breast Cancer Not Treated with Adjuvant Anti-HER2-Targeted Therapy: A 10-Year Follow-Up Study

Breast Care ◽

10.1159/000520793 ◽

2021 ◽

Author(s):

Jenni S. Liikanen ◽

Marjut Leidenius ◽

Heikki Joensuu ◽

Tuomo J. Meretoja

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Disease Free Survival ◽

Survival Outcomes ◽

Her2 Expression ◽

Term Survival ◽

Node Negative ◽

Her2 Breast Cancer

Introduction Human epidermal growth factor receptor 2 (HER2) expression is considered an unfavourable prognostic factor in early breast cancer when the patients are not treated with HER2-targeted therapy. However, the long-term prognostic importance of HER2-expression in small (≤1 cm, stage pT1a-b), node-negative HER2+ breast cancer is still incompletely known. Methods A retrospective analysis was performed based on a prospectively collected database including patients with pT1 breast cancer operated at the Helsinki University Hospital, Finland, between March 2000 and April 2006. In this database, 44 patients with pT1a-bN0M0, HER2+ cancer, not treated with adjuvant anti-HER2-targeted therapy (the HER2+ group) and 291 pT1a-bN0M0, hormone receptor positive, HER2- negative cancers (the ER+/HER2- group) were identified and included in the study. Survival outcomes were analysed using the Kaplan-Meier method. Results The median follow-up time was 9.7 years after primary breast surgery. Ten-year distant disease-free survival (DDFS) was 84.0% in the HER2+ group and 98.2% in the ER+/HER2- group (p < 0.001). Ten-year overall survival was only 78.5% in the HER2+ group, but 91.7% in the ER+/HER2- group (p = 0.09). Conclusions Cancer HER2-status is strongly associated with unfavourable DDFS during the first decade of follow-up in patients with small (pT1a-bN0M0) breast cancer when adjuvant anti-HER2-targeted treatment is not administered.

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Predominance of RAD21 and ERBB2 amplification and progesterone receptor positivity in tumors of the right breast support breast cancer lateralization.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12557 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12557-e12557

Author(s):

Zachary Spigelman ◽

Jo-Ellen Murphy

Keyword(s):

Breast Cancer ◽

Progesterone Receptor ◽

Cancer Patients ◽

Breast Tumors ◽

Left Breast ◽

Breast Cancers ◽

Her2 Expression ◽

Breast Cancer Patients ◽

The Right ◽

Chi Square Analysis

e12557 Background: Biologic lateralization broadly impacts breast cancer. Malignancies originating in the left breast compared to the right breast tend to be more frequent, larger and of poorer prognosis. Left breast tumors respond differently to HER2-neu signaling and have lateralized Ki67 expression. In a prior study a right-left asymmetry in the neutrophil/lymphocyte ratio (NLR) of breast cancers was identified (ASCO 2018, e13094). As a follow-up, retrospective analysis of results from comprehensive genomic profiling (CGP) of right and left side breast cancer specimens was performed to determine a potential genomic etiology for the observed NLR lateralization. Methods: Tumors from 43 consecutive breast cancer patients underwent analysis for all classes of genomic alterations by hybrid capture-based CGP (Foundation Medicine). The CGP results from the 25 left- and 18 right-sided breast cancer samples were analyzed along with the histologic grade and status of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Results: In this cohort of advanced breast cancer patients (stage 3-4), no statistically significant differences in lateralization were identified based on patient age, tumor stage, or frequency of ER or Her2 expression (Table). A predominance of PR positivity (p=0.14 chi square analysis) and amplifications in the ERBB2 (p=0.37) and RAD21 (p=0.08) genes were detected in right side tumors. Conclusions: Together with the prior study, trends in asymmetry based on genomic, pathologic, and immunohistologic differences have been detected in breast cancers, including an increased incidence of ERBB2 and RAD21 amplification in right-side breast tumors in this cohort. The predominance of lower PR positivity in the left breast tumors may be due to preferential hypermethylation, consistent with reports that it mediates biologic lateralization changes, downregulates PR expression, and alters amplification rates. Epigenetic methylation, may contribute to asymmetric breast cancer biology and have implications for therapeutic strategy. Further study is warranted.[Table: see text]

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Breast cancer ER, PR, and HER2 expression variance by germline cancer predisposition genes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10526 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10526-10526

Author(s):

Grace Wei ◽

Marilin Rosa ◽

Maxine Chang ◽

Brian J. Czerniecki ◽

Xia Wang

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Breast Cancer Diagnosis ◽

Cancer Predisposition ◽

Tumor Evolution ◽

Breast Cancers ◽

Her2 Expression ◽

Expression Levels ◽

Genetic Test Results ◽

Predisposition Genes

10526 Background: The association between breast cancer characteristics and survival with estrogen receptor (ER) and progesterone receptor (PR) expression has been primarily studied via binomial categories, ER-positive and ER-negative. In order to better characterize germline genetic influences on these markers, we investigated their IHC expression semi-quantitatively in cancer predisposition germline pathogenic variant (PV) carriers of the following genes: BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, ATM, CHEK2, and Lynch syndrome genes. The HER2 expression was also analyzed. Methods: We conducted a retrospective chart review of patients with germline panel genetic testing for cancer predisposition genes at Moffitt Cancer Center’s GeneHome clinic. Inclusion criteria included 1) women ≥18 years old, 2) breast cancer diagnosis, 3) cancer predisposition germline panel genetic test results, 4) available ER and PR expression levels, and 5) available HER expression and/or amplification status. ER, PR, and HER2 status were compared between PV carriers and non-PV carriers via Mann-Whitney U at p>0.05. Results: A total of 847 cases were reviewed for the study. Among 658 patients with a breast cancer diagnosis and complete ER PR data, 365 cases (55.5%) were non-PV carriers and 293 cases (44.5%) carried a PV in at least one of the genes listed above. Among 635 cases with available HER2 expression/amplification status, 355 (55.9%) cases were non-PV carriers and 288 (45.4%) cases were PV-carriers. When compared with non-PV carrier controls, BRCA1 PV carriers’ breast tumors had significantly lower ER and/or PR expression. Further, BRCA2 and TP53 PV tumors also displayed moderately lower ER expression. Contrarily, CHEK2 tumors displayed higher ER and PR expression compared to controls. Further, BRCA1 and BRCA2 PV carriers were more likely to have HER2- breast cancers. Conclusions: Differences in ER, PR, HER2 expression levels were observed in germline PV carrier breast cancers, signaling differential impacts by germline PVs on the tumor evolution process. It is likely that tumor differences in PV carriers influence responses to therapies, including hormone therapy, anti-HER2 therapy, and subsequent survival.[Table: see text]

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