HER2-positive invasive lobular carcinoma: a rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study

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

“…We are the first to show that ERBB2amplified 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][4][5][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.…”

“…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 carcinomas responded to targeted anti‐HER2 therapy, and this effect was not seen in HER2‐positive lobular carcinoma [3]. Da Ros on the contrary did not find differences in recurrence rate between HER2‐positive ILBC and NST carcinomas, but showed a broader variation in mutational landscape in ILBC than in NST, postulating the more frequent molecular alterations as the leading cause for worse prognosis [8].…”

“…ILBCs are usually clinically poorly defined or diffuse tumors and due to lack of associated calcifications often pose diagnostic imaging difficulties and underestimation of tumor stage [ 1 , 2 ]. Although luminal‐type lobular carcinomas have potentially favorable features such as an ER/PR positive, HER2‐negative phenotype with low proliferative activity, there is still a controversy whether luminal‐type ILBCs do differ in outcome from stage‐matched invasive ductal carcinomas of no special type (NST) [ 1 , 2 , 3 ]. 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 ].…”

“…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 ].…”

“…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 ]. However, no data are available on molecular gene alterations and on the immunohistochemical protein expression profile in the HER2‐positive lobular subtype.…”