23P Clinical, pathological and gene expression features of HER2-low breast cancer

Schettini, Francesco; Chic, Núria; Brasó-Maristany, Fara; Paré, Laia; Pascual, Tomás; Conte, Benedetta; Martínez-Sáez, Olga; Adamo, Bárbara; Vidal, María; Fernández-Martínez, Aranzazu; González-Farré, Blanca; Sanfeliu, Esther; Perrone, Giuseppe; Villagrasa, Patricia; Gregori, Joaquín Gavilá; Barrios, Carlos H.; Lluch, Ana; Jiménez, M. Martín; Placido, Sabino De; Prat, Aleix

doi:10.1016/j.annonc.2020.03.159

Cited by 8 publications

(10 citation statements)

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“…According to previous studies, between 40% and 50% of patients with breast cancer have tumors with low HER2 expression [15][16][17]. Here we observed a slightly higher proportion of HER-low cases (64% of all breast cancers).…”

Section: Discussionsupporting

confidence: 66%

“…However, their study did not further stratify the patients based on HR status, which is an important parameter in the clinic. Francesco et al were the rst to compare the prognosis of HER2-low and HER2-0 by HR status, and found no statistically signi cant differences these two groups, regardless of HR status [16]. We suggest that it is more important to determine whether HER2-low or HER2-0 status is associated with a poorer prognosis in luminal or triple negative breast cancer.…”

Section: Discussionmentioning

confidence: 58%

“…If, for example, HER2-low status was associated with a poorer prognosis than HER2-positive status, this would prompt a re-evaluation of the utility of anti-HER2 therapies in HER2-low patients. Although there is one report in which the prognoses of HER2-low and HER2-0 breast cancer were compared [16], further studies are required. We therefore carried out a retrospective analysis of HER2-low versus HER2-negative patients.…”

Section: Introductionmentioning

confidence: 99%

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The Frequency of Low HER2 Expression in Breast Cancer and A Comparison of Prognosis Between Patients With HER2-Low and HER2-Negative Breast Cancer By HR Status

Horisawa

Adachi

Takatsuka

et al. 2021

Preprint

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PurposeThe DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2-low patients with that of HER2-negative patients. MethodsWe retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quantified the overall frequency of breast cancer patients with a new HER2-low subtype that was defined by an immunohistochemistry score of IHC1+ or IHC2+/ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 amplification (HER2-0). ResultsLow HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309(6.3%) were HR-negative. Among HER2-0 patients, 681(13.9%) were HR-positive and 157(3.2%) were HR-negative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically significant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group.ConclusionHER2-low patients did not have a significantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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The Frequency of Low HER2 Expression in Breast Cancer and A Comparison of Prognosis Between Patients With HER2-Low and HER2-Negative Breast Cancer By HR Status

Horisawa

Adachi

Takatsuka

et al. 2021

Preprint

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“…This is major, considering that inter-pathologists agreement on HER2 scoring has been demonstrated to be potentially suboptimal, especially for 1+ and 2+ immunohistochemical score. 43 Additionally, interpretation of in situ hybridization results has changed through time 25 , 26 ; however, the possibility to homogeneously retrospectively reassess all samples for HER2 status according to the latest ASCO/CAP guidelines was not feasible. 25 Another issue is that patients pertained to different databases and thus were not necessarily consecutively enrolled.…”

Section: Discussionmentioning

confidence: 99%

T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study

Schettini

Conte

Buono³

et al. 2021

ESMO Open

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Background The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant. Results Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival ( P = 0.095). Conclusions Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials.

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“…Patients with HER2-low BC spam a heterogeneous group, immunohistochemically comprised of a majority of hormone receptor (HR) positive tumors (65–83%), while the rest has HR-negative tumors [ 17 , 18 ]. As such, HR-positive, HER2-low BC has a distinct molecular profile than HR-negative, HER2-low BC: while the first is enriched with luminal subtypes, the latter demonstrates a predominance of the basal-like subtype, underlining major genetic, clinicopathological, and prognostic differences within the group [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

The Exciting New Field of HER2-Low Breast Cancer Treatment

Eiger

Agostinetto

Saúde-Conde

et al. 2021

Cancers

108

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Since human epidermal growth factor receptor-2 (HER2) characterization, going through clinical research and regulatory approval of HER2-targeted therapies, much has elapsed and is still unfolding. Hitherto, only breast cancer (BC) patients with HER2 immunohistochemistry 3+ or with HER2 gene fluorescence in-situ hybridization (FISH) amplification (a.k.a., HER2-positive BC) have benefited from anti-HER2 agents. In recent years, however, much of the research effort has been expanded, with positive outcomes being reached for formerly known HER2-negative BC that yet express HER2 to some degree (HER2 immunohistochemistry 1+ or 2+, but FISH negative) and are currently being classified as HER2-low BC for the purpose of trial enrollment. In this sense, our aim is to review the body of evidence of HER2-low BC that led to the study of first-generation anti-HER2 agents, like trastuzumab, and how they have failed to achieve any clinical applicability in this setting. In addition, we review new data that is leading to the growing success of the new generation of drugs, especially the promising HER2-directed antibody–drug conjugates. A narrative review is also performed regarding the rationale behind the consolidated and ongoing clinical trials studying anti-HER2 agents in combination with unrelated agents, such as immunotherapy, endocrine therapy, and CDK4/6 inhibitors. Hopefully, all this ongoing research effort will be able to extend the survival benefits seen with anti-HER2 agents in HER2-positive disease, at least to some degree, to the greater proportion of patients with HER2-low BC.

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23P Clinical, pathological and gene expression features of HER2-low breast cancer

Cited by 8 publications

References 0 publications

The Frequency of Low HER2 Expression in Breast Cancer and A Comparison of Prognosis Between Patients With HER2-Low and HER2-Negative Breast Cancer By HR Status

The Frequency of Low HER2 Expression in Breast Cancer and A Comparison of Prognosis Between Patients With HER2-Low and HER2-Negative Breast Cancer By HR Status

T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study

The Exciting New Field of HER2-Low Breast Cancer Treatment

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