Lobular breast carcinoma after COVID-19: what has changed in prevalence and molecular profile?ABSTRACT
Introduction: Invasive lobular carcinoma (CLI) is a type of cancer that originates in the mammary glands. It is distinguished by presenting multiple histological and molecular patterns, with the main subtypes being luminal (A and B) and triple negative. The COVID-19 pandemic has significantly impacted health services, with the suspension of elective operations and the prioritization of care for severe cases.
Objective: To evaluate the possible changes in the prevalence and characteristics of CLI in the post-pandemic period, with emphasis on the distribution by age group, histological patterns, and molecular subtypes.
Method: The prevalence of carcinoma was identified by core biopsy and/or segmental resection of the breast, within the histological standards of lobular carcinomas, and the comparison of histological findings was based on the immunohistochemical profile of the tumors (molecular classification).
Results: The highest prevalence was between the fifth and seventh decades, peaking in the fifth (41-50 years) similar to pre-pandemic data. The classic histological pattern of the CLI was the most common in all age groups. Among the classical CLIs, luminal molecular subtype A was the most prevalent. There was no statistically significant difference between the prevalence of luminal CLI B and triple negative. Triple-negative tumors predominantly exhibited the pure histiocytoid pattern.
Conclusion: There was a higher prevalence of CLI in women in the fifth decade, with a predominance of the classic pattern and the luminal subtype A in the post-pandemic period.
KEYWORDS:
Lobular breast carcinoma; Breast neoplasms; COVID-19; Molecular characterization; Tumor biomarkers
RESUMO
Introdução: Carcinoma lobular invasivo (CLI) é um tipo de câncer que se origina nas glândulas mamárias. Se distingue por apresentar múltiplos padrões histológicos e moleculares, sendo os principais subtipos o luminal (A e B) e o triplo negativo. A pandemia de COVID-19 impactou significativamente os serviços de saúde, com a suspensão de operações eletivas e a priorização do atendimento de casos graves.
Objetivo: Avaliar as possíveis alterações na prevalência e características do CLI no período pós-pandêmico, com ênfase na distribuição por faixa etária, padrões histológicos e subtipos moleculares.
Método: A prevalência do carcinoma foi identificada por core biopsy e/ou ressecção segmentar da mama, dentro dos padrões histológicos dos carcinomas lobulares, e a comparação dos achados histológicos baseou-se no perfil imuno-histoquímico dos tumores (classificação molecular).
Resultados: A maior prevalência foi entre a quinta e sétima décadas, com pico na quinta (41-50 anos), semelhante aos dados pré-pandêmicos. O padrão histológico clássico do CLI foi o mais comum em todas as faixas etárias. Entre os CLIs clássicos, o subtipo molecular luminal A foi o mais prevalente. Não houve diferença estatisticamente significativa entre a prevalência de CLI luminal B e triplo negativo. Tumores triplo negativos exibiram predominantemente o padrão histiocitoide puro.
Conclusão: Houve maior prevalência de CLI em mulheres na quinta década com predominância do padrão clássico e do subtipo luminal A no período pós-pandêmico.
PALAVRAS-CHAVE:
Carcinoma lobular de mama; Neoplasias da mama; COVID-19; Caracterização molecular; Biomarcadores tumorais
INTRODUCTION
Invasive lobular carcinoma (CLI) is a special breast neoplasm, occupying the second place in prevalence among all breast cancers, especially in the postmenopausal age group.1 It originates in the lobules and terminal ducts of the mammary gland (terminal lobular duct unit), presenting unique biological and molecular characteristics, which are the result of the inactivation of the CDH1 gene and the consequent absence of the E-cadherin protein, providing this neoplasm with a multicenter/multifocal pattern, perhaps bilateral, in addition to infiltrative and diffuse growth, contrasting with the more cohesive pattern of highly prevalent breast neoplasms.2
Its diagnosis is based on the characteristic growth pattern and phenotype of the neoplastic cells with the respective subtypes: classical, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type.3,4 Despite the histological particularities, the treatment of CLI is mainly based on clinical staging and TNM, which depends on the size of the primary tumor, the presence of regional lymph node metastases and their number, as well as the presence of distant organ metastases.3
It is important to emphasize that there are differences in prognosis between two tumors of the same clinical stage and the same histopathological characteristics. That is why priority is given to individualized therapy, which depends on the molecular characteristics of breast cancer, individualized by genotyping, emphasizing that different molecular subtypes have varying prognosis. Standard prognostic factors depend on age, disease stage, tumor grade, histological type, status of resection margins, and presence of lymphovascular invasion.5 Predictive markers of therapeutic response are the ER and HER2 receptors, which is why determining the status of the hormone receptors ER, PR and HER2 is considered an essential factor to make additional decisions about the therapy of this cancer.6.7
It is important to recognize that the COVID-19 pandemic has significantly impacted health services around the world, with the suspension of elective operations and the prioritization of care for severe cases. In this context, it is plausible to hypothesize that the epidemiology of CLI may have undergone changes, with a possible increase in the incidence of cases diagnosed in more advanced stages due to the interruption of screening and timely treatment.8
Within this semantics, The present study aimed to analyze the prevalence and clinical-pathological characteristics of CLI cases, with emphasis on the distribution by age group, histological patterns and molecular subtypes, diagnosed in a high-complexity hospital in southern Brazil, between the years 2020 and 2024, which marks the trans and post-COVID-19 pandemic period.
METHOD
This research was approved by the Human Research Ethics Committee of the Evangelical Mackenzie Faculty of Paraná, Curitiba, PR, Brazil - CAAE no. 81810124.4.0000.0103. It was conducted in accordance with the applicable ethical principles. The anonymity of the patients and the confidentiality of the data collected were guaranteed. It was observational, analytical, and retrospective and was carried out at the Mackenzie Evangelical University Hospital, Curitiba, PR, Brazil. The prevalence of carcinoma was identified by core biopsy and/or segmental resection of the breast, within the histological standards of lobular carcinomas, and the comparison of histological findings was based on the immunohistochemical profile of the tumors (molecular classification).
All cases of CLI diagnosed at the hospital in the period from January 1, 2020 to December 31, 2024 were included.
Data were collected from medical records, including demographic information (age, gender), diagnostic data, histopathological report, and immunohistochemistry.
The histopathological slides were reviewed by a pathologist specialized in the breast to confirm the diagnosis and classify the tumors according to the histological standards (classical, alveolar, solid, trabecular, pleomorphic, histiocytoid and with signet ring cells).
Immunohistochemistry
Immunohistochemical studies were performed to determine the expression profile of the following markers: hormone receptors (estrogen and progesterone), HER2/NEU, Ki67 and E-cadherin. The results were used to classify tumors into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Triple Negative) and to analyze the expression of E-cadherin in the different histological patterns of CLI.
Statistical analysis
Descriptive statistical methods (absolute and relative frequencies, means, medians, standard deviations) were used to present the results. To compare the histological and immunohistochemical characteristics of the tumors, appropriate statistical tests were used, such as chi-square or Fisher’s test for categorical variables, and Student’s t-test or Mann-Whitney test for continuous variables. The level of statistical significance was set at 5% (p < 0.05).
RESULTS
Epidemiology of the data
There were 53 cases of CLI diagnosed between January 1, 2020 and December 31, 2024. Of these lobular carcinomas, all cases found (100%) affected the female gender with a mean age of 57.7 years.
The incidence was between the fourth (between 31-40 years) and tenth decade of life (between 90-100 years). Quantification between the age groups was heterogeneous and is shown in Table 1.
In the 4th decade (between 31-40 years), only two cases were diagnosed. Among the histological patterns found, one was classic lobular carcinoma and the other was pleomorphic lobular carcinoma and histiocytoid. Table 2 shows the characteristics of the tumors found in this age group, as well as their molecular classification.
In the 5th, 6th and 7th decades of life, the patterns were heterogeneous, both in terms of histological classification and molecular classification. Tables 3, 4 and 5 reveal the patterns for these age groups.
Interestingly, there were some tumors, especially of classical pattern, that were classified as Luminal B; however, all tumors of this molecular classification revealed the same immunohistochemical profile, i.e. estrogenic and progesterone positive, without HER2/NER overexpression.
No cases were found in the 9th decade of life. In the 10th there was only one diagnosed as lobular carcinoma in the signet ring, with molecular classification of Luminal B.
DISCUSSION
In the present study, the prevalence of lobular carcinomas and their respective molecular patterns was evaluated according to age group in the cases diagnosed during the study period.
The results found corroborate the scientific literature in pre-pandemic periods, demonstrating that lobular carcinoma of the classic variant is still the most frequent histological type among lobular carcinomas of the breast, corresponding to 58.4% of cases.9 This finding is in agreement with several studies that point to the classic variant as the most prevalent, accounting for up to 80% of lobular carcinomas in some geographic ranges of the globe, especially the United States of America.10
The analysis of the age distribution of the patients revealed a higher prevalence of lobular carcinomas in the fifth decade of life (41-50 years), with 32.07% of the cases diagnosed in this range. This period corresponds to the moment of menopausal transition, in which several hormonal changes occur that can influence the development of breast cancer.
Although the fifth decade of life stood out as the most prevalent, a significant incidence of lobular carcinomas was also observed in the sixth (51-60 years) and seventh (61-70 years) decades of life, with identical percentages of 24.53%. Despite these differences, there was no statistical significance between the fifth, sixth, and seventh decades, suggesting that advanced age and cumulative alteration of epigenetics may also be a risk factor for the development of this type of invasive lobular breast cancer.11
These results indicate that most classic lobular carcinomas (41.50%) have the luminal A pattern, characterized by the expression of hormone receptors (estrogen and progesterone) and absence of HER2 receptor expression. This molecular profile is associated with a better prognosis and greater sensitivity to hormone therapy. These results corroborate data in the literature, which sometimes shows even a higher percentage, reaching 55-70% in terms of the prevalence of these tumors among other institutions.12
The analysis of hormone receptor expression and HER2/NEU in all histological subclasses of lobular carcinomas revealed that most of them have the luminal A pattern, regardless of the histological variant. This finding suggests that luminal A molecular profile is a common factor in most lobular carcinomas, regardless of their microscopic appearance.13
In the cases in which the pleomorphic pattern was identified, it was observed that most of them (six cases between 8-75%) were associated with mixed carcinomas, i.e., tumors that present characteristics of different histological patterns. Lobular carcinomas, in which the pure pleomorphic pattern is predominant, were less common (2-8 cases - 25%).11
Regarding triple-negative carcinomas, in which there is no expression of hormone receptors and HER2, ER and PR concomitantly, it was observed that all cases (100%) exhibited a single histological pattern, which was pure histiocytoid.14 This pattern is a rare variant of CLI, characterized by the presence of tumor cells with morphology similar to histiocytes, i.e., abundant and eosinophilic cytoplasm. This histological pattern has been associated with more aggressive CLI behavior, with a higher risk of extranodal metastasis and local recurrence. This molecular profile is associated with a worse prognosis compared with other subtypes of CLI, due to the lack of specific targeted therapies and the greater aggressiveness of the tumor. Curiously, not all those who present the mixed histiocytoid profile present heterogeneity of molecular profile, ranging from Luminal A or B. However, due to the scarcity of the number of these tumor patterns, the literature fails to establish a molecular pattern establishing a global prevalent pattern, and this study is an initiator in this perspective.14.15
The results of the present study are valuable on the clinical and histopathological profile of CLI five years after the COVID-19 pandemic, contributing to a better understanding of this disease and to the development of more effective diagnostic and treatment strategies.
Limitations
It is important to note that this study has some limitations, such as the sample size and the retrospective nature of the analysis. Future studies with larger samples and a prospective design are needed to confirm our findings and deepen our knowledge about lobular carcinoma of the breast.
CONCLUSION
The identification of specific histological and molecular patterns in different age groups can contribute to a better understanding of CLI biology and optimize treatment strategies, especially in the context of possible changes resulting from the COVID-19 pandemic.
References
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Central Message
The COVID-19 pandemic has significantly impacted health services around the world, with the suspension of elective operations and the prioritization of care for severe cases. In this context, it is plausible to hypothesize that the epidemiology of invasive lobular carcinoma of the breast may have undergone changes, with a possible increase in the incidence of cases diagnosed in more advanced stages, perhaps due to the interruption of screening and timely treatment.
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Perspective
It is appropriate to evaluate possible changes in the prevalence and characteristics of invasive lobular carcinoma of the breast in the post-pandemic period, with emphasis on distribution by age group, histological patterns, and molecular subtypes. Thus, it will be possible to assess how much the pandemic may have influenced the prevalence and characteristics of this carcinoma in the post-pandemic period, with emphasis on distribution by age group, histological patterns, and molecular subtypes.
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How to cite this article
de Souza VV, Ribas CAPM, Collaço LM, Chaves LCL, Beltrame B, Rossoni C, Giovanini AF. Carcinoma lobular de mama após a COVID-19: o que mudou na prevalência e no perfil molecular? BioSCIENCE. 2026;84:e00006. https://doi.org/10.55684/2026.84.en.e00006
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Funding:
Partly by the Coordination for the Improvement of Higher Education Personnel - Brazil (CAPES) - Funding code 001
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Data availability:
Data are available from the corresponding author upon reasonable request.
Edited by
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Associate Editor:
Nerlan Tadeu Gonçalves de Carvalho https://orcid.org/0009-0009-8777-5485
Data are available from the corresponding author upon reasonable request.
