Abstract:The development of novel anti-HER2 drugs opens new treatment options for women with breast cancers, including lower expression of HER2. The epidemiology and clinical outcome of metastatic HER2-low breast cancer remain not well described. We designed a retrospective cohort study of the 2010–2017 National Cancer Database (NCDB) was designed to compare the overall survival of HER2-low and HER2-zero de novo metastatic breast cancer with systemic therapy. Multivariable Cox regression models were performed to estima… Show more
“…A 2022 retrospective analysis of 391 breast cancer patients concluded HER2‐low cancers correlated with lower‐grade cancers and longer OS than HER2‐negative patients 17 . Similarly, a 2022 study analyzing metastatic breast cancer patients in the NCDB database found HER2‐negative status was associated with higher survival in both hormone receptor negative and positive groups 18 …”
Section: Discussionmentioning
confidence: 99%
“…17 Similarly, a 2022 study analyzing metastatic breast cancer patients in the NCDB database found HER2-negative status was associated with higher survival in both hormone receptor negative and positive groups. 18 A 2021 analysis of the PRAEGNANT prospective registry of advanced breast cancers found no significant difference in survival between HER2-low vs HER2-negative advanced triple-negative breast cancers or in advanced hormone receptor-positive breast cancers. 19 We suspect this discrepancy may arise from the larger power of our study (n = 2033 vs. our 24,636).Our analysis found patient race was a significant variable impacting survival.…”
IntroductionWe explored characteristics and clinical outcomes of HER2‐negative and HER2‐low metastatic breast cancers using real‐world data.MethodsWe queried the National Cancer Database to identify MBC patients that were HER2‐low or HER2‐negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity‐match analysis were performed to identify correlates of survival.ResultsExcluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2‐negative and 72.1% were HER2‐low. There were no relevant demographic differences between the groups. HER2‐low tumors were half as likely to have concomitant hormone receptor‐positive status (p < 0.01). The 3‐year survival rate among hormone receptor‐negative patients was 33.8% for HER2‐low and 32.2% for HER2‐negative (p < 0.05), and 60.9% and 55.6% in HER2‐low and HER2‐negative cases among hormone receptor‐positive patients (p < 0.05), respectively. HER2‐low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91–0.99) and remained superior with propensity‐matching (HR = 0.92, 95% CI 0.89–0.96). In a subset analysis isolated to hormone receptor‐positive cases, HER2‐low remained correlated with improved survival (HR = 0.93, 95% CI 0.89–0.98) with propensity‐matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02–1.02) and Black race (HR = 1.26, 95% CI 1.20–1.32) [all p < 0.01].ConclusionsIn the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2‐low tumors compared to HER2‐negative tumors in MBC.
“…A 2022 retrospective analysis of 391 breast cancer patients concluded HER2‐low cancers correlated with lower‐grade cancers and longer OS than HER2‐negative patients 17 . Similarly, a 2022 study analyzing metastatic breast cancer patients in the NCDB database found HER2‐negative status was associated with higher survival in both hormone receptor negative and positive groups 18 …”
Section: Discussionmentioning
confidence: 99%
“…17 Similarly, a 2022 study analyzing metastatic breast cancer patients in the NCDB database found HER2-negative status was associated with higher survival in both hormone receptor negative and positive groups. 18 A 2021 analysis of the PRAEGNANT prospective registry of advanced breast cancers found no significant difference in survival between HER2-low vs HER2-negative advanced triple-negative breast cancers or in advanced hormone receptor-positive breast cancers. 19 We suspect this discrepancy may arise from the larger power of our study (n = 2033 vs. our 24,636).Our analysis found patient race was a significant variable impacting survival.…”
IntroductionWe explored characteristics and clinical outcomes of HER2‐negative and HER2‐low metastatic breast cancers using real‐world data.MethodsWe queried the National Cancer Database to identify MBC patients that were HER2‐low or HER2‐negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity‐match analysis were performed to identify correlates of survival.ResultsExcluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2‐negative and 72.1% were HER2‐low. There were no relevant demographic differences between the groups. HER2‐low tumors were half as likely to have concomitant hormone receptor‐positive status (p < 0.01). The 3‐year survival rate among hormone receptor‐negative patients was 33.8% for HER2‐low and 32.2% for HER2‐negative (p < 0.05), and 60.9% and 55.6% in HER2‐low and HER2‐negative cases among hormone receptor‐positive patients (p < 0.05), respectively. HER2‐low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91–0.99) and remained superior with propensity‐matching (HR = 0.92, 95% CI 0.89–0.96). In a subset analysis isolated to hormone receptor‐positive cases, HER2‐low remained correlated with improved survival (HR = 0.93, 95% CI 0.89–0.98) with propensity‐matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02–1.02) and Black race (HR = 1.26, 95% CI 1.20–1.32) [all p < 0.01].ConclusionsIn the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2‐low tumors compared to HER2‐negative tumors in MBC.
“…12 Several studies reported that HER2-low tumors have a lower pathological complete response and better prognosis. 10,13,14 HER2-low disease is more frequently seen in HR-positive BC (luminal biology) than in TNBC (60%-66% vs. 33%-37%), and most of the HER2-low tumors are HR-positive (88%). 10,15 After correction for HR expression, there are only marginal differences in clinicopathological characteristics and prognosis for HER-2 low compared with HER2-zero BC.…”
Section: What Is Her2-low Bc?mentioning
confidence: 99%
“…It is reported that the gene expression analysis of stage I‐III TNBC suggests that drivers of resistance to neoadjuvant treatment differ between HER2‐zero and HER2‐low tumors 12 . Several studies reported that HER2‐low tumors have a lower pathological complete response and better prognosis 10,13,14 . HER2‐low disease is more frequently seen in HR‐positive BC (luminal biology) than in TNBC (60%–66% vs. 33%–37%), and most of the HER2‐low tumors are HR‐positive (88%) 10,15 …”
The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)‐status to HER2‐low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2‐low expression has emerged as a targetable biomarker, and anti‐HER2 antibody‐drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2‐low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor–positive and triple‐negative BC needs to be reconsidered, as approximately half of these BCs are HER2‐low. Although there are different therapeutic agents for hormone receptor–positive and hormone receptor–negative HER2‐low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2‐low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.
“… 4 Approximately 60% of HER2− breast cancers [including hormone receptor (HR)+ and HR− disease] may be classified as HER2-low. 7 , 8 , 9 , 10 Figure 1 Evolution of HER2 classification and current categories . HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization.…”
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