Distinct breast cancer phenotypes in BRCA 1/2 carriers based on ER status

Rosenberg, Shai; Devir, Michal; Kaduri, Luna; Grinshpun, Albert; Miner, Vardiella; Hamburger, Tamar; Granit, Avital; Nissan, Aviram; Maymon, Ofra; Peretz, Tamar

doi:10.1007/s10549-022-06851-6

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…A recent study showed that ERBB2 is a key pathway regulator in germline BRCA-associated tumors, both in HER2-positive and HER2-negative cases. 25 Whether this was related to unidentified epigenetic mechanisms and/or a potential influence of HER2-low tumors remains unclear. These data suggest that BRCA2 may be involved in the regulation of ERBB2 expression, or, alternatively, that DNA alterations resulting from deficient BRCA2 protein may indirectly affect ERBB2 gene transcription.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we report for the first time a higher prevalence of HER2‐low tumors in patients with BRCA2 PVs. A recent study showed that ERBB2 is a key pathway regulator in germline BRCA ‐associated tumors, both in HER2‐positive and HER2‐negative cases 25 . Whether this was related to unidentified epigenetic mechanisms and/or a potential influence of HER2‐low tumors remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Schettini,

Blondeaux,

Molinelli

et al. 2024

Cancer

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BackgroundBreast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset.MethodsWomen aged ≤40 years with newly diagnosed early‐stage HER2‐negative BC (HER2‐0 and HER2‐low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test and Student t‐test were used to describe variable distribution between HER2‐0 and HER2‐low. Associations with HER2‐low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease‐free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05.ResultsOf 3547 included patients, 32.3% had HER2‐low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple‐negative (TN) tumors. HER2‐low vs. HER2‐0 BC were more often of grade 1/2 (p < .001), hormone receptor–positive (p < .001), and node‐positive (p = .003). BRCA2 PVs were more often associated with HER2‐low than BRCA1 PVs (p < .001). HER2‐low versus HER2‐0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2‐low (p = .014) and TN and luminal A‐like in HER2‐0 (p = .019) showed the worst DFS.ConclusionsIn young patients with HER2‐negative BC and germline BRCA1/2 PVs, HER2‐low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal‐like disease. HER2‐low status was associated with a modestly improved prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Schettini,

Blondeaux,

Molinelli

et al. 2024

Cancer

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Tumor analysis of BRCA carriers reveals genomic similarities although separated by time

Falick Michaeli,

Granit Mizrahi,

Azria

et al. 2024

Discov Onc

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Among the dominant pathogenic genes (PG) in breast cancer are BRCA1/2 . Knowing whether a patient carry one of these alterations is meaningful as it affects management. A substantial question is to what extent are the genomic profile of a tumor and its characteristics affected by the germline profile of BRCA1/2 and what is the possible contribution of other environmental factors. Here, we compared the molecular characteristics of two subsequent primary breast cancers in three women (6 primary breast cancers) BRCA PG carriers, and in two of them also a primary lung cancer. Comparing two different tumors in the same patient neutralizes the contribution of other germline changes, and may demonstrate possible effects of other external insults occurring between the first and second tumor. Nonetheless, epigenetic changes resulting from early life events will be present in all tumors that the patient has developed. Our analysis suggests that tumors arising from the same tissue in the same patient share similar molecular characteristics, albeit occurring in different times, as the patient is exposed to a variety of external stimuli. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-024-01577-x.

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Distinct breast cancer phenotypes in BRCA 1/2 carriers based on ER status

Cited by 2 publications

References 26 publications

Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Tumor analysis of BRCA carriers reveals genomic similarities although separated by time

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