Clinical outcomes in patients with triple negative or HER2 positive lobular breast cancer: a single institution experience

Okines, Alicia; Irfan, T.; Asare, B.A.; Mohammed, Kabir; Osin, Peter; Nerurkar, Ashutosh; Smith, Ian; Parton, Marina; Ring, Alistair; Johnston, Stephen; Turner, Nicholas C.

doi:10.1007/s10549-021-06432-z

Cited by 2 publications

(6 citation statements)

References 42 publications

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“…We are the first to show that ERBB2 ‐amplified invasive lobular carcinomas similarly to ERBB2 ‐amplified NST breast carcinomas do exhibit concomitant CDK12 / ERBB2 gene amplification. This phenomenon likely explains why ERBB2 ‐amplified ILBC behaves in a more similar clinical manner to ERBB2 ‐amplified NST carcinomas as has been already postulated in sparse previous literature sources on NST breast carcinomas [3–6,29]. However, it is of note that therapy failure is best addressed in a neoadjuvant setting, which in our series has not been the case and should be potentially addressed in future studies.…”

Section: Discussionsupporting

confidence: 72%

“…Regarding prognosis and therapy responses, sparse data are available on HER2-positive ILBCs. In 2022, Okina et al reported that HER2-positive ILBC especially in advanced stage had worse prognosis and shortened OS than HER2-positive NST carcinomas and postulated the inconsistent administration of anti-HER2 agents as a possible explanation [6]. A similar observation was reported in a recent French study, which found that only HER2-positive invasive ductal 11 of 18 ERBB2/CDK12 coamplification in invasive lobular breast carcinoma carcinomas responded to targeted anti-HER2 therapy, and this effect was not seen in HER2-positive lobular carcinoma [3].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a rare subgroup of HER2‐positive ILBC tends to be of higher histological grade, more often nodal positive and ER/PR negative [ 4 , 5 ]. These poor prognostic features have been described in association with resistance to anti‐HER2 therapy in the HER2‐positive ILBC subgroup [ 3 , 6 ]. Molecular and oncological features of luminal type ILBC have been widely studied [ 3 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features

Forster‐Sack,

Zoche,

Pestalozzi

et al. 2024

The Journal of Pathology CR

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Most invasive lobular breast carcinomas (ILBCs) are luminal‐type carcinomas with an HER2‐negative phenotype (ERBB2 or HER2 un‐amplified) and CDH1 mutations. Rare variants include ERBB2‐amplified subtypes associated with an unfavorable prognosis and less response to anti‐HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2‐amplified ILBC and compared these characteristics with ERBB2‐unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin‐embedded formalin‐fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast‐specific markers was tested by immunohistochemistry (IHC). Hybrid capture‐based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2‐amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2‐unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2‐positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2‐amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2‐amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2‐unamplified ILBC. CDK12/ERBB2 co‐amplification may explain the poor prognosis and therapy resistance of ERBB2‐amplified ILBC.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features

Forster‐Sack,

Zoche,

Pestalozzi

et al. 2024

The Journal of Pathology CR

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“…Approximately 80–90% of primary ILCs express estrogen receptor (ER), have a luminal A phenotype and can be considered classic ILC 5 , 6 . Approximately 5% of ILCs are triple negative (TN) and frequently exhibit a luminal phenotype, implying that this subtype has a different biology than the majority of TN breast cancer (TNBC) that is dominated by basal-like tumors 1 , 7 , 8 .…”

Section: Mainmentioning

confidence: 99%

“…Approximately 80-90% of primary ILCs express estrogen receptor (ER), have a luminal A phenotype and can be considered classic ILC 5,6 . Approximately 5% of ILCs are triple negative (TN) and frequently exhibit a luminal phenotype, implying that this subtype has a different biology than the majority of TN breast cancer (TNBC) that is dominated by basal-like tumors 1,7,8 . short-term platinum-based regimen was to exploit the immunological effects of carboplatin and potentially synergize with PD-L1 blockade and not to induce direct cytotoxic effects.…”

mentioning

confidence: 99%

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial

et al. 2023

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Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial (NCT03147040), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.5 mg ml–1 min–1) as immune induction for 12 weeks and atezolizumab (PD-L1 blockade; triweekly) from the third week until progression. Four of 23 evaluable patients had a partial response (17%), and 2 had stable disease, resulting in a clinical benefit rate of 26%. From these six patients, four had triple-negative ILC (TN-ILC). We observed higher CD8+ T cell infiltration, immune checkpoint expression and exhausted T cells after treatment. With this GELATO trial, we show that ILC-specific clinical trials are feasible and demonstrate promising antitumor activity of atezolizumab with carboplatin, particularly for TN-ILC, and provide insights for the design of highly needed ILC-specific trials.

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Clinical outcomes in patients with triple negative or HER2 positive lobular breast cancer: a single institution experience

Cited by 2 publications

References 42 publications

ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features

ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial

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