scholarly journals Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3695
Author(s):  
Matthias Christgen ◽  
Gábor Cserni ◽  
Giuseppe Floris ◽  
Caterina Marchio ◽  
Lounes Djerroudi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Special Treatment ◽  
Molecular Characteristics ◽  
Lobular Breast Cancer ◽  
Her2 Positive ◽  
Comprehensive Overview ◽  
Invasive Lobular Breast Cancer

Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.

Trends in breast cancer mortality according to molecular subtypes: A population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola
Keyword(s):  
Breast Cancer ◽  
Cancer Mortality ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Mortality ◽  
Treatment Strategies ◽  
Luminal A ◽  
Her2 Positive ◽  
Mortality Trends ◽  
Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

scholarly journals Bayesian Networks established functional differences between breast cancer subtypes

2018 ◽  
Author(s):  
Lucía Trilla-Fuertes ◽  
Andrea Zapater-Moros ◽  
Angelo Gámez-Pozo ◽  
Jorge M Arevalillo ◽  
Guillermo Prado-Vázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Bayesian Networks ◽  
Triple Negative ◽  
Breast Cancer Subtypes ◽  
Molecular Profile ◽  
Molecular Characteristics ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Hormonal Receptor

AbstractBreast cancer is a heterogeneous disease. In clinical practice, tumors are classified as hormonal receptor positive, Her2 positive and triple negative tumors. In previous works, our group defined a new hormonal receptor positive subgroup, the TN-like subtype, which has a prognosis and a molecular profile more similar to triple negative tumors. In this study, proteomics and Bayesian networks were used to characterize protein relationships in 106 breast tumor samples. Components obtained by these methods had a clear functional structure. The analysis of these components suggested differences in processes such as metastasis or proliferation between breast cancer subtypes, including our new subtype TN-like. In addition, one of the components, mainly related with metastasis, had prognostic value in this cohort. Functional approaches allow to build hypotheses about regulatory mechanisms and to establish new relationships among proteins in the breast cancer context.Author SummaryBreast cancer classification in the clinical practice is defined by three biomarkers (estrogen receptor, progesterone receptor and HER2) into hormone receptor positive, HER2+ and triple negative breast cancer (TNBC). Our group recently described a new ER+ subtype with molecular characteristics and prognosis similar to TNBC. In this study we propose a mathematical method, the Bayesian networks, as a useful tool to study protein interactions and differential biological processes in breast cancer subtypes, characterizing differences in relevant processes such as proliferation or metastasis and associated them with patient prognosis.

scholarly journals HER2 Positive and HER2 Negative Classical Type Invasive Lobular Carcinomas: Comparison of Clinicopathologic Features

2021 ◽  
Vol 28 (3) ◽  
pp. 1608-1617
Author(s):  
Lin He ◽  
Ellen Araj ◽  
Yan Peng
Keyword(s):  
Breast Cancer ◽  
Lobular Carcinoma ◽  
Tumor Biology ◽  
Case Series ◽  
Classical Type ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Clinicopathologic Features ◽  
Her2 Positive ◽  
Her2 Breast Cancer

Human epidermal growth factor receptor 2 (HER2) positive (+) classical type invasive lobular carcinoma (cILC) of the breast is extremely rare and its clinicopathologic features have not been well characterized. We compared features of HER2(+) and HER2 negative (−) cILCs. A total of 29 cases were identified from the clinical database at our institution from 2011-2019; 9 were HER2(+) cILC tumors and 20 were HER2(−) cILC tumors. The results reveal that HER2(+) cILC group had significantly increased Ki-67 expression and reduced estrogen receptor (ER) expression compared to HER2(−) cILC group (both p < 0.05). In addition, HER2(+) cILCs tended to be diagnosed at a younger age and more common in the left breast, and appeared to have a higher frequency of nodal or distant metastases. These clinicopathologic features suggest HER2(+) cILC tumors may have more aggressive behavior than their HER2(−) counterpart although both groups of tumors showed similar morphologic features. Future directions of the study: (1) To conduct a multi-institutional study with a larger case series of HER2(+) cILC to further characterize its clinicopathologic features; (2) to compare molecular profiles by next generation sequencing (NGS) assay between HER2(+) cILC and HER2(−) cILC cases to better understand tumor biology of this rare subset of HER2(+) breast cancer; and (3) to compare molecular characteristics of HER2(+) cILC and HER2(+) high grade breast cancer in conjunction with status of tumor response to anti-HER2 therapy to provide insight to management of this special type of low grade breast cancer to avoid unnecessary treatment and related toxicity

Exploring New Targets and Publication Tendency of Triple Negative Breast Cancer: A 20-Year Bibliometric Analysis

2021 ◽  
Author(s):  
Xiaonan Sheng ◽  
Huijuan Dai ◽  
Yonggang Song ◽  
Xueyun Ma
Keyword(s):  
Breast Cancer ◽  
Bibliometric Analysis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Research Focus ◽  
The Past ◽  
The Usa

Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it lacks an efficient target treatment. Here, we aimed to gain knowledge on the development of TNBC research and explore potential treatment strategies.Methods: We analyzed 14,389 publications on TNBC from the Web of Science (WOS) over the past 20 years, from 2000 to 2020, using bibliometric methods. We evaluated the publication tendency of TNBC and the contributions of different countries. Institutions and journals with the highest number of TNBC publications were screened. Finally, the research focus of the TNBC publications were also analyzed.Results: TNBC publications have significantly increased in the past 20 years, with elevated relative research interest (RRI). The USA has the most TNBC-related publications with high quality, and China is the country with the most rapid growth tendency in TNBC publications. The University of Texas System is the institution with the most TNBC publications. Breast Cancer Research and Treatment is the journal that published the most TNBC-related publications. The top 30 publications with high citations are also listed. The researches focusing on TNBC in the past 20 years were separated into four main clusters: tumor biology, TNBC therapies, treatment sensitivity, and gene mutations. The research focus in TNBC ranked by appearing years reflects the development of TNBC treatment strategy, showing that targeting tumor immunity is now the main focus in TNBC research. Conclusions: Using bibliometric analysis, we initially revealed the increasing interest in TNBC research and summarized the publication tendency of TNBC. We also reported focused topics screened from publications in the past 20 years, indicating the main problems and research objectives of TNBC for the first time. Immune-related topics are becoming the focus of TNBC research.

The impact of screening mammography in women age 40-49 as a function of tumor biology.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 113-113
Author(s):  
John C. Ruckdeschel ◽  
William V. Rees ◽  
Brett T Parkinson ◽  
Thomas Belnap ◽  
Braden D. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Tumor Biology ◽  
Screening Mammography ◽  
Her2 Status ◽  
Screening Mammogram ◽  
Interval Cancers ◽  
Her2 Positive ◽  
The Impact

113 Background: Mammographic screening for women 40-49 years of age remains controversial based on results from earlier large scale, controlled mammography trials. Methods: From 2002-2006, 871 women aged 40-49 were diagnosed with breast cancer at Intermountain. The charts of all patients without a record of a screening mammogram at Intermountain (n= 436) were reviewed to confirm that they had not had a screening mammogram in the prior two years at any facility (Interval Cancers) and their survival was compared to 435 women who had their cancer diagnosed on a screening exam (Screen Detected). All patients were followed for at least 5 years via the tumor registry. Results: Stage distribution for Screen Detected/Interval cancers was 25.3/6.4% stage 0, 36.8/24.8% stage I, 24.6/35.6% stage II, 6.9/20.4% stage III and 0.5/3.4% stage IV. Overall, 67 patients (7.7%) did not have complete staging data. Overall survival was significantly better (p<.0001) for 40-49 year old women with Screen Detected compared to those with Interval cancers. 702 (79.6%) had ER/PR status recorded (83.5% ER/PR positive). Women with DCIS or LCIS did not have tissue sent for markers. 679 patients (76.9%) had HER2 status recorded (78.8% HER2 neg). Of the patients with both HER2 and ER/PR status recorded 10.4% were “triple negative.” Survival following screening mammography was significantly enhanced for women who were ER/PR positive (p<0.0001), HER2 negative (p=0.0065), or HER2 positive (p=0.0013). Survival was not improved by screening mammography for women who were ER/PR negative (p=0.3818) or for women who were triple negative (p=0.416). Conclusions: A minority of women age 40-49 who develop breast cancer (13%) have biologic features suggestive of aggressive disease and, after 5 years of follow up, they are not benefitted by screening mammography. The remaining 87% are clearly benefitted by screening mammography. Our results suggest that the discrepancies noted in the screening mammography trials in 40-49 year old women may have resulted from population variations in the proportion of women with unfavorable biology. Based in part on these results, we continue to recommend regular screening in the 40-49 year old cohort.

Prognosis of pT1a,bN0 breast cancer: Perception from the French oncology community—Results from the EURISTIC survey.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11607-e11607
Author(s):  
Marc Spielmann ◽  
David Azria ◽  
Jean Marc Classe ◽  
Florence Dalenc ◽  
Clarisse Dromain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Perceived Risk ◽  
Triple Negative ◽  
Early Stage ◽  
Tumour Size ◽  
Tumor Biology ◽  
Her2 Positive ◽  
Triple Negative Tumor ◽  
Negative Tumor

e11607 Background: Although most early-stage breast tumors have a favourable outcome, some subgroups carry a higher recurrence risk. The objective of the EURISTIC Survey was to evaluate the perception French physicians have of the prognostic risk associated with the biopathological characteristics of tumors in pT1a,b N0 breast cancer. Methods: This 38 item postal survey was developed by an expert panel. 2,000 physicians involved in breast cancer treatment were contacted. Specialities involved were medical and radiation oncologists, surgeons, radiologists and pathologists. Results: The survey was conducted between September and December 2012. A total of 663 physicians responded (response rate = 33%). They stated treating an average of 50 breast cancer patients per month. 58% of physicians reported that tumour size was not considered a major parameter in this clinical setting. In the absence of an adjuvant treatment, the prognosis of T1a,bN0 carcinoma was perceived better if HR-positive rather than HER2-positive or triple-negative with a "positive" prognosis perception rated by 83%, 21% and 8% of physicians respectively. For pT1a,bN0 tumors, the criteria with the highest perceived prognostic risk were ranked as follows: HER2+ (29%), HR- (20%) elevated tumor grade (20%) and triple negative tumor (14%). The average size threshold for a "negative" prognostic rated tumor was 18 mm. This threshold was scaled up for HR-positive carcinoma (22 mm) and scaled down for HER2-positive (10mm) or triple negative carcinoma (7mm). Between 4 and 17 mm, there was a linear correlation between tumor size and perceived risk of recurrence with HER2-positive tumors always carrying a worse prognostic than HR-positive tumor (Table). Conclusions: French physicians have the perception that HER2-positivity and triple negative tumor biology strongly impact the prognosis of pT1a,b N0 carcinoma, independent of tumor size. [Table: see text]

The Effect of Biology in the Treatment of Small Breast Tumors

2013 ◽  
pp. 25-31
Author(s):  
Jose Perez-Garcia ◽  
Eva Muñoz-Couselo ◽  
Javier Cortes
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Tumors ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Negative ◽  
Screening Programs ◽  
Small Breast ◽  
Number Of Patients

Although the outcome of small (T1a/b) node-negative breast tumors is generally excellent, in the absence of prospective clinical trials, we are limited to data derived from retrospective analyses. Overall, the 10-year overall mortality rate is approximately 20%, while the 10-year breast cancer-specific mortality is in the range of 4% to 8% among this population in the absence of systemic therapy. This clearly reflects that many patients die of causes not related to breast cancer. Due in large part to breast cancer screening programs, the incidence of small tumors is increasing. There is consequently a growing interest in identifying factors that negatively affect the prognosis of these patients. Several studies have shown that patients with triple-negative and HER2+ tumors have a worse prognosis compared with hormone-receptor–positive, HER2- small breast cancers. However, the recent explosion of knowledge of the molecular characteristics of tumors is opening a new way to address cancer. Different genomic assays are currently available to help better predict the outcome of breast cancer patients. However, none of these techniques have been specifically evaluated in patients with small (T1a/b) node-negative tumors, and only a small number of patients with these tumors were included in those studies. In addition, very limited data are available about the role of these assays in patients with triple-negative or HER2-positive cancers. Although a chemotherapy-based strategy might be useful for triple-negative or HER2-positive T1b tumors, more information is urgently needed in order to optimize the treatment of our patients.

Association between tumor biology and occult lymph node metastases before and after primary neoadjuvant therapy (NAT) for patients with early breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 518-518
Author(s):  
Hans-Christian Kolberg ◽  
Cornelia Kolberg-Liedtke ◽  
Maja Krajewska ◽  
Ingo Bauerfeind ◽  
Tanja N. Fehm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Early Breast Cancer ◽  
Lymph Node Metastases ◽  
Axillary Dissection ◽  
Triple Negative ◽  
Tumor Biology ◽  
Her2 Positive ◽  
Before And After ◽  
Node Metastases

518 Background: Scientific efforts aim at a reduction of axillary morbidity through reduced axillary intervention among patients with early breast cancer. However, it is still unclear if this approach is feasible in all subtypes based on their risk of axillary involvement. We analyzed the association of tumor biology and occult axillary involvement with data from arms A and B of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were included if they presented with a clinically negative axilla before NAT (arms A and B) and stratified according to tumor biology. All patients received SLNB before NAT, in cases of negative SLNB without further axillary surgery (Arm A) and in cases of positive SLNB (Arm B) with SLNB and axillary dissection after NAT. Logistic and linear regression analyses were carried out to evaluate the association between tumor biology and axillary involvement before and after NAT. Results: Of the 1022 patients in arms A and B of the SENTINA trial 926 were evaluable for this analysis. Of these, 27.9% had triple negative (TN), 16.3% hormone receptor (HR) and HER2 positive (triple positive = TP), 47.6% HR positive and HER2 negative (luminal) and 8.2% HR negative and HER2 positive (HER2) tumors. 39.7% of the luminal, 28.9% of the HER2, 19% of the TN and 47% of the TP tumors had involved SLN before NAT. Subgroup comparisons showed a significant difference between luminal and TN (p < 0.0001), whereas the differences between luminal and TP (p = 0.115) and HER2 (p = 0.077) were not statistically significant. The 317 patients with involved SLN prior to NAT received SLNB and axillary dissection after completion of NAT. The analysis after NAT showed trends for lower rates of involved lymph nodes for the high-risk groups (TN 20% / TP 14.3% / HER2 8.7%) compared to luminal tumors (27.6%) without reaching statistical significance. Conclusions: Our analysis demonstrates that among patients enrolled in the SENTINA trial, patients with triple negative disease have the lowest risk for occult lymph node metastases at initial presentation. Our results do not justify more intense local intervention among patients with triple negative breast cancer.

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