Prevalence, treatment patterns, and prognosis of low estrogen receptor-positive (1% to 10%) breast cancer: a single institution’s experience in Korea

Park, Yeon Hee; Karantza, Vassiliki; Calhoun, Shawna; Park, Sehhoon; Lee, Sohee; Kim, Jiyeon; Yu, Jong Han; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Aktan, Gursel; Marsico, Mark

doi:10.1007/s10549-021-06309-1

Cited by 11 publications

(10 citation statements)

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“…Our findings are in line with other studies, which have likewise shown comparable pathological response rates and survival for Low-ER breast cancer and TNBC 18 , 23 – 26 . In our cohort, only nodal positivity and higher T stage (and not ER/PR expression group) were significantly associated with RFS and OS on multivariable analysis, consistent with previous work 24 .…”

Section: Discussionsupporting

confidence: 93%

“…Our study does have limitations, including the relatively small number of patients in the Low-ER group and lack of central testing for ER/PR. The Low-ER subgroup comprised 12.6% of our study population; this finding is consistent with previous studies which have shown that this group accounts for 8–16% of HER2-negative ER/PR-negative breast cancers, with different definitions of ER/PR negativity being utilized across studies 18 , 23 , 24 . Although lack of central ER/PR testing may be considered a limitation, utilization of local testing is representative of the real-world setting.…”

Section: Discussionsupporting

confidence: 90%

“…Patients with ER/PR expression 1–10% in our cohort were treated with adjuvant endocrine therapy at a low rate of 20%. Other studies have described similar low usage of endocrine therapy among patients with Low-ER breast cancer 23 , 24 . Notably, as opposed to other studies, all patients in our cohort were treated after the 2010 ASCO/CAP guideline update which defined the cutoff for ER positivity as 1% expression by immunohistochemistry; however, adjuvant endocrine therapy use was still modest in the Low-ER group despite being classified as “ER-positive” per the 2010 guidelines.…”

Section: Discussionmentioning

confidence: 68%

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Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

et al. 2022

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Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression <1% and absence of HER2 amplification/overexpression. HER2-negative breast cancer with low ER/PR expression (1–10%) has a gene expression profile similar to TNBC; however, real-world treatment patterns, chemotherapy response, endocrine therapy benefit, and survival outcomes for the Low-ER group are not well known. 516 patients with stage I-III HER2-negative breast cancer and ER/PR expression ≤10% who were enrolled in a multisite prospective registry between 2011 and 2019 were categorized on the basis of ER/PR expression. TNBC (ER and PR < 1%) and Low-ER (ER and/or PR 1–10%) groups comprised 87.4% (n = 451) and 12.6% (n = 65) of patients, respectively. Demographic, clinical, and treatment characteristics, including prevalence of germline BRCA1/2 mutation, racial and ethnic distribution, and chemotherapy use were not different between TNBC and Low-ER groups. No difference was observed in recurrence-free survival (RFS) and overall survival (OS) between TNBC and Low-ER groups (3-year RFS 82.5% versus 82.4%, respectively, p = 0.728; 3-year OS 88.0% versus 83.4%, respectively, p = 0.632). Among 358 patients receiving neoadjuvant chemotherapy, rates of pathologic complete response were similar for TNBC and Low-ER groups (49.2% vs 51.3%, respectively, p = 0.808). The HER2-negative Low-ER group is often excluded from TNBC clinical trials assessing novel treatments (immunotherapy and antibody-drug conjugates), thus limiting efficacy data for newer effective therapies in this group. Given that HER2-negative Low-ER disease displays clinical characteristics and outcomes similar to TNBC, inclusion of this group in TNBC clinical trials is encouraged.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 68%

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Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

et al. 2022

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“…In NeoPACT, 16% of enrolled patients had low ER−PR (1%-10%), and we noted comparable pCR rates between patients with low vs negative ER−PR. A growing body of literature indicates that HER2/ERBB2 negative, low ER−PR breast cancer displays clinical characteristics, chemotherapy response, and outcomes similar to TNBC . The low ER−PR group comprises 8% to 16% of HER2/ERBB2 negative breast cancer and is often excluded from TNBC clinical trials, thus limiting efficacy data for newer therapies in this group .…”

Section: Discussionmentioning

confidence: 99%

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer

Sharma,

Stecklein,

Yoder

et al. 2024

JAMA Oncol

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ImportanceAddition of pembrolizumab to anthracycline-based chemotherapy improves pathologic complete response (pCR) and event-free survival (EFS) in triple-negative breast cancer (TNBC). The efficacy of anthracycline-free chemoimmunotherapy in TNBC has not been assessed.ObjectiveTo assess the efficacy of the anthracycline-free neoadjuvant regimen of carboplatin and docetaxel plus pembrolizumab in TNBC.Design, Setting, and ParticipantsThis was an open-label phase 2 clinical trial including a single group of patients with stage I to III TNBC enrolled at 2 sites who received neoadjuvant carboplatin and docetaxel plus pembrolizumab every 21 days for 6 cycles. Participants were enrolled from 2018 to 2022.Intervention or ExposureCarboplatin (with an area under the free carboplatin plasma concentration vs time curve of 6) and docetaxel (75 mg/m2) plus pembrolizumab (200 mg) every 21 days for 6 cycles. Myeloid growth factor support was administered with all cycles.Main Outcomes and MeasuresPrimary end point was pathologic complete response (pCR) defined as no evidence of invasive tumor in breast and axilla. The secondary end points were residual cancer burden, EFS, toxicity, and immune biomarkers. RNA isolated from pretreatment tumor tissue was subjected to next-generation sequencing. Specimens were classified as positive or negative for the 44-gene DNA damage immune response (DDIR) signature and for the 27-gene tumor immune microenvironment (TIM; DetermaIO) signature using predefined cutoffs. Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated using standard criteria. Programmed cell death-ligand 1 (PD-L1) testing was performed using a standard immunohistochemical assay.ResultsAmong the eligible study population of 115 female patients (median [range] age, 50 [27-70] years) who enrolled from September 2018 to January 2022, 39% had node-positive disease. pCR and residual cancer burden 0 + 1 rates were 58% (95% CI, 48%-67%) and 69% (95% CI, 60%-78%), respectively. Grade 3 or higher immune-mediated adverse events were observed in 3.5% of patients. sTILs, PD-L1, DDIR, and TIM were each predictive of pCR in multivariable analyses. The areas under curve for pCR were 0.719, 0.740, 0.699, and 0.715 for sTILs, PD-L1, DDIR, and TIM, respectively. Estimated 3-year EFS was 86% in all patients; 98% in pCR group and 68% in no-pCR group.Conclusions and RelevanceThe findings of the phase 2 clinical trial indicate that neoadjuvant carboplatin and docetaxel plus pembrolizumab shows encouraging pCR and 3-year EFS. The regimen was well tolerated, and immune enrichment as identified by various biomarkers was independently predictive of pCR. These results provide data on an alternative anthracycline-free chemoimmunotherapy regimen for patients who are not eligible for anthracycline-based regimens and support further evaluation of this regimen as a chemotherapy de-escalation strategy in randomized studies for TNBC.Trial RegistrationClinicalTrials.gov Identifier: NCT03639948

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“…Recently, several studies demonstrated that patients with ER low-positive HER2-negative breast cancer have similar outcomes as compared to triple-negative breast cancer (TNBC) patients 10 – 14 . ER low-positive breast tumors have comparable progesterone receptor (PR) levels 12 , 15 , tumor grade 10 – 13 , 16 and Ki-67 expression 11 , 13 , 16 to TNBC and are usually classified as basal-like or HER2-enriched 11 , 15 , 17 . Intermediate ER expression of 10–50% is common in ~5–10% of breast tumors 18 , 19 and we hypothesize that this group might share basal-like features with TNBC similar to the ER low-positive group.…”

Section: Introductionmentioning

confidence: 99%

Immune landscape of breast tumors with low and intermediate estrogen receptor expression

et al. 2023

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Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials. Stromal tumor-infiltrating lymphocytes (sTILs) and other immune parameters are higher in TNBC compared to ER-positive breast cancer, but it is unknown whether lower ER levels are associated with more inflamed tumor microenvironments (TME). We collected a consecutive series of primary tumors from 173 HER2-negative breast cancer patients, enriched for tumors with ER expression between 1 and 99% and found levels of stromal TILs, CD8 + T cells, and PD-L1 positivity in breast tumors with ER 1–9% and ER 10–50% to be comparable to tumors with ER 0%. Expression of immune-related gene signatures in tumors with ER 1–9% and ER 10–50% was comparable to ER 0%, and higher than in tumors with ER 51–99% and ER 100%. Our results suggest that the immune landscape of ER low tumors (1–9%) and ER intermediate tumors (10–50%) mimic that of primary TNBC.

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Prevalence, treatment patterns, and prognosis of low estrogen receptor-positive (1% to 10%) breast cancer: a single institution’s experience in Korea

Cited by 11 publications

References 26 publications

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer

Immune landscape of breast tumors with low and intermediate estrogen receptor expression

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