Medullary Carcinoma Of Breast Research Articles

Baicalin Promotes Apoptosis of Human Medullary Breast Cancer via the ERK/p38 MAPK Pathway

Objectives: The present study aims to examine the effects of baicalin on the human medullary breast carcinoma (MBC) cell line Bcap-37 and to determine whether baicalin regulates Bcap-37 cell apoptosis through the ERK/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell assay were utilized to measure the effects of baicalin on the proliferation and migration ability of Bcap-37 cells, respectively. Flow cytometer analysis was implied to detect the effects of baicalin on Bcap-37 cell apoptosis. Real-time quantitative polymerase chain reaction (RT-PCR) was conducted to observe the influence of baicalin on mRNA expressions of apoptosis-related genes. Western blot was executed to further explore the action of baicalin on apoptosis-related proteins. PD98059 (a specific inhibitor of ERK) and SB203580 (a specific inhibitor of p38 MAPK) were used to further clarify the intrinsic mechanism of baicalin regulating apoptosis in Bcap-37 cells. Results: Compared with the control group, baicalin significantly inhibits the proliferation activity of Bcap-37 cells in a concentration- and time-dependent manner, with a p-value < 0.05. The transwell assay indicated that the migration viability of cells decreased further, followed by the increased concentration of baicalin, and the p-value had a statistical difference. Besides, flow cytometry was conducted to assess the effects of baicalin on the early and late apoptosis rates of Bcap-37 cells, and results showed that baicalin highly promoted the apoptosis level both at the early and late stages with a statistical difference in a concentration-dependent manner ( p < 0.05). Results of RT-PCR presented that, compared with the control group, baicalin significantly activated the mRNA expression of Bax, p38, and p-ERK1 and abolished the mRNA expression of Bcl-2 in every dosing group in a concentration-dependent way ( p < 0.05). Western blot exhibited that, compared with the control group, baicalin promoted the protein expression of caspase-3, caspase-9, Bax, p38, P-ERK, and p53 while playing an opposite function to Bcl-2 in each dosing group ( p values have statistical differences). At last, PD98059 and SB203580 were applied to explore the potential mechanism of baicalin in apoptosis promotion. And results revealed that, compared with the group treated with baicalin alone, protein expression of Bax, p38, p-ERK, caspase-3, and caspase-9 was downregulated obviously in the group treated with both baicalin and PD98059 or SB203580 ( p < 0.05). The p53 expression inhibition showed a difference only when compared to the group adding PD98059. Compared with the blank group, a statistical difference was only observed in Bcl-2 expression in the group treated with baicalin in combination with PD98059 or SB203580 ( p < 0.05). Interestingly, a p53 expression difference was only displayed between the blank group and the group treated with baicalin and SB203580 ( p < 0.05). Conclusion: Our study observed that baicalin inhibits the proliferation and migration ability of Bcap-37 cells. In addition, baicalin induces cell apoptosis via the ERK/p38 MAPK signal pathway.

Comparison of the prognosis of medullary breast carcinoma and invasive ductal carcinoma: a SEER-based study.

Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients. A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy. There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors. MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.

A risk stratification model to predict chemotherapy benefit in medullary carcinoma of the breast: a population-based SEER database

Whether patients with medullary breast carcinoma (MBC) receive chemotherapy is controversial. Therefore, the aim of our study was to screen out patients with MBC who benefit from chemotherapy. We enrolled 618 consecutive patients with MBC from The Surveillance, Epidemiology, and End Results (SEER) database (2010–2018). Cox regression analysis was used to identify independent prognostic factors. Next, a nomogram was constructed and evaluated using calibration plots and the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Kaplan‒Meier curves were used to evaluate the overall survival (OS) benefit of chemotherapy in different risk groups. A total of 618 MBC patients were involved in our study, and an 8:2 ratio was used to randomly split them into a training cohort (n = 545) and a validation cohort (n = 136). Next, a nomogram predicting 3- and 5-year OS rates was constructed based on the five independent factors (age at diagnosis, T stage, N status, subtype and radiation). The nomogram AUCs for 3- and 5-year OS (training set: 0.793 and 0.797; validation set: 0.781 and 0.823) and calibration plots exhibited good discriminative and predictive ability. Additionally, a novel risk classification system for MBC patients demonstrated that we do not have enough evidence to support the benefit effect of chemotherapy for the high-risk group as the result is not statistically significant (total population: p = 0.180; training set: p = 0.340) but could improve OS in the low-risk group (total population: p = 0.001; training set: p = 0.001). Our results suggested that chemotherapy should be selected more carefully for high-risk groups based on a combination of factors and that the possibility of exemption from chemotherapy should be confirmed by more clinical trials in the future.

Medullary Carcinoma of the Breast: About A Case

Breast Medullary carcinoma, is a histologic form with inflammatory stroma requiring strict histological criteria for its definition. It represents less than 5% of breast tumors. The aim of this work is to analyze the epidemiological, clinical, evolutive characteristics and therapeutic results, through a retrospective study of medullary breast carcinoma histologically confirmed and treated in Aile 8, department of the university hospital of Casablanca.

Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type.

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 ( P < 0.001), no significant difference in the number of CD4 ( P = 0.154), CD8 ( P = 0.199), and a significantly higher CD8/FoxP3 ratio ( P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage ( P = 0.031), smaller tumor size ( P = 0.010), and negative lymph node status ( P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

MEDULLARY CARCINOMA OF THE BREAST-EPIDEMIOLOGY, THE PATTERN OF CARE, AND TREATMENT OUTCOME: EXPERIENCE FROM THE TERTIARY CANCER CARE CENTER

Objectives: Medullary breast carcinoma is a very rare subtype of invasive ductal carcinoma breast which accounts for about 1–7% of all breast carcinoma. The natural history of this uncommon histological subtype is unknown because of the lack of adequate reported data in the literature and the rare variety of this tumor. In our retrospective analysis, we have tried to identify demographic clinicopathological features and treatment outcomes of this rare subtype. Methods: Between January 2012 and December 2017, total of 1271 breast carcinoma cases were identified, and clinic pathological, demographic profile, and treatment received were recorded from the medical records file. American joint committee on Cancer tumor, node, and metastasis system was used for staging. Results: Out of 1271 breast carcinomas, 19 histologically confirmed medullary carcinoma cases were identified and constitute about 1.5% of the total case. About 78% of patients were with Stage II and Stage III disease at the time of diagnosis. Eleven patients were initially treated with MRM followed by adjuvant chemotherapy and radiotherapy. Eight patients received neoadjuvant chemotherapy followed by surgery and radiotherapy. In addition to cytotoxic chemotherapy, two patients received trastuzumab also. None of the patients received hormone therapy as all the patients were hormone receptor-negative. Conclusions: Out of all invasive carcinoma, approximately 1.5% of cases were medullary carcinoma. About 90% of cases were triple-negative. Triple-negative breast cancer is usually associated with poor outcomes but medullary carcinoma despite being triple-negative, patients with medullary carcinoma have a good chance of long-term survival.

Hormone Receptor Status May Impact the Survival Benefit Between Medullary Breast Carcinoma and Atypical Medullary Carcinoma of the Breast: A Population-Based Study.

BackgroundA rare subtype of breast cancer, atypical medullary carcinoma of the breast (AMCB), shows a highly adverse prognosis compared to medullary carcinoma of the breast (MBC). The current study aimed to establish a correlated nomogram for the identification of the prognostic factors of AMCB and MBC.MethodsKaplan–Meier and Cox regression analyses were applied to data acquired from the Surveillance, Epidemiology and End Results (SEER) database for 2004 to 2013 to analyse tumour characteristics and overall survival. Propensity score matching (PSM) analysis was performed to determine the overall survival (OS) among those with AMCB and MBC. A predictive nomogram was created, and the concordance index (C-index) was used to predict accuracy and discriminative ability.ResultsA total of 2,001 patients from the SEER database were diagnosed with MBC between 2004 and 2013, including 147 patients diagnosed with AMCB. The number of diagnoses gradually increased in both groups. Cox analysis of multivariate and Kaplan–Meier analysis showed that older age (HR = 3.005, 95% CI 1.906–4.739) and later stage were significantly associated with poor prognosis, while cancer-directed surgery was an independent protective factor (HR = 0.252, 95% CI 0.086–0.740). In the HR-negative stratification analysis, older age (HR = 2.476, 95% CI 1.398–4.385), later stage and histological type (HR=0.381, 95% CI 0.198-0.734) were found to be independent prognostic factors for low standard survival. The log-rank analysis demonstrated significantly worse prognostic factors for patients with AMCB than for those with MBC (P = 0.004). A nomogram (C-index for survival = 0.75; 95% CI 0.69–0.81) was established from four independent prognostic factors after complete identification.ConclusionsMBC is rare, and cancer-directed surgery, older age, and later stage are independently linked with prognosis. In the HR negative population, AMCB patients show a worse survival gain than those with MBC.

Medullary breast carcinoma: a pathogenic review and immunohistochemical study using tissue microarray.

Introduction:Medullary breast carcinomas (MBCs) are distinguished by circumscribed, high-grade morphology with dense chronic inflammation; they are associated with the basal phenotype but have a relatively good prognosis.Methods:This study aimed to review the clinicopathological features of MBCs diagnosed at the Department of Pathology, Singapore General Hospital and correlate them with immunohistochemical expression of hormonal markers and c-erbB-2, the basal markers p53, cytokeratin (CK) 14, epidermal growth factor receptor (EGFR) and 34BE12, and the follow-up outcome.Results:Using Ridolfi's criteria for histologic reviews, 62 patients previously diagnosed as having ‘typical MBC’ (n = 26), ‘atypical MBC’ (n = 32) and ‘invasive carcinoma with focal medullary-like features’ (n = 4) were re-classified as follows: ‘typical MBC’ (n = 6; 9.7%), ‘atypical MBC’ (n = 46; 74.2%), and ‘non-medullary infiltrating carcinoma’ (n = 10; 16.1%). Clinicopathological parameters, including ethnicity, age, tumour size and concurrent ductal carcinoma in situ (DCIS), showed no statistically significant correlation with review diagnoses and immunohistochemical findings. Presence of lymphovascular invasion and nodal stage were significantly correlated with recurrence and breast cancer-related deaths, respectively. ER negativity was significantly correlated with triple positivity for basal markers CK14, EGFR and 34BE12, which comprised patients who showed a significantly decreased disease-free survival rate within a 10–15-year follow-up period.Conclusions:Lymphovascular invasion and high nodal stage as well as triple negativity among typical and atypical MBCs that have basal-like phenotype represent a portion of invasive carcinomas with medullary features that may have poor outcomes in this otherwise relatively good prognostic group.

Medullary Carcinoma of Breast: A Case Report and Review of Literature

Medullary Carcinoma of Breast: A Case Report and Review of Literature

Prognosis and Survival of Medullary Carcinoma of the Breast

Medullary breast carcinoma (MBC) is a rare tumor, representing 3% to 5% of invasive breast carcinomas. The World Health Organization defines it as a well-circumscribed invasive tumor, composed of poorly differentiated cells, arranged in sheets, without gland formation and a scarce collagen stroma with the presence of a very prominent lymphoplasmacytic infiltrate.

English

Ridolfi et al. in 1977 defined medullary breast carcinoma (MBC) as one of the invasive and malignant subtypes of breast cancer.1 It is a rare breast malignancy accounting for 5 % of breast carcinomas.2 Although MBC is considered as having good prognosis, patients reported as triple-negative breast cancers are associated with aggressive clinical behaviour and poor prognosis.3 Also factors like local invasion, evidence of regional metastasis, etc. will determine the progress of this type of cancer.

Peptide specifically binding to human medullary breast carcinoma Bcap-37 cells selected by phage display in vivo and its property as well as combination effect

Objective To investigate the property and the combination effect of the peptide specifically binding to human medullary breast cancer Bcap-37 cells by using phage display in vivo and to provide molecular targeting probe for early diagnosis of breast cancer. Methods The human medullary breast carcinoma Bcap-37 cells tumor-bearing nude mice model was prepared and three rounds in vivo were performed by using Ph.D.-C7CTM phage display peptide library. The distribution of screened phages in tumors and normal tissues was detected by using immunohistochemistry. The affinity of monoclonal phage to Bcap-37 cells was identified by using enzyme linked immunosorbent assay (ELISA). The positive monoclonal phage DNA was taken and sequenced, and the sequence with high repetition rate was selected to synthesize peptide by using chemical methods. Optical molecular probe was prepared and fluorescence molecular imaging was used to test its specificity and targeting ability for breast transplantation tumor of tumor-bearing nude mice in vivo. Results The recovery rate of phage in the third round screening in vivo was 107.2 times than that in the first round. Immunohistochemical results showed that the phages binding to the tumor tissues were increased successively with the increasing screening rounds in vivo. The number of phages binding to tumor tissues was more than that binding to normal tissues (lung, skeletal muscle, liver and kidney). The absorbancy (A) value of section scanning image in the tumor tissues was higher than that in the normal tissues, and the difference was statistically significant different (P < 0.05). ELISA results showed that 22 phages (affinity≥2) among the 50 randomly selected monoclonal phage were positive. After DNA sequencing analysis of the positive monoclonal phage, 4 repeat amino acid sequences were obtained. The fluorescein isothiocyanate-labelled (FITC)-CSPLNTRFC with the highest repetition rate was synthesized for FITC-CSPLNTRFC peptide. Bcap-37 cells tumor-bearing nude mice model assay in vivo showed that FITC-CSPLNTRFC peptide could significantly enriched in the breast xenograft tissues. Conclusion CSPLNTRFC peptide specifically binding to human medullary breast cancer Bcap-37 cells can be screened out successfully by using phage display in vivo, which will be helpful to vitro studies on the early diagnosis of breast cancer. Key words: Breast neoplasms; Peptide library; Phage display; Specifically binding peptide

Competing Risk Analyses of Medullary Carcinoma of Breast in Comparison to Infiltrating Ductal Carcinoma

The aim of current study was to use competing risk model to assess whether medullary carcinoma of the breast (MCB) has a better prognosis than invasive ductal carcinomas of breast cancer (IDC), and to build a competing risk nomogram for predicting the risk of death of MCB. We involved 3,580 MCB patients and 319,566 IDC patients from Surveillance, Epidemiology, and End Results (SEER) database. IDC was found to have a worse BCSS than MCB (Hazard ratio (HR) > 1, p < 0.001). The 5-year cumulative incidences of death (CID) was higher in IDC than MCB (p < 0.001). Larger tumor size, increasing number of positive lymph nodes and unmarried status were found to worsen the BCSS of MCB (HR > 1, p < 0.001). We found no association between ER, PR, radiotherapy or chemotherapy and MCB prognosis (p > 0.05). After a penalized variable selection process, the SH model-based nomogram showed moderate accuracy of prediction by internal validation of discrimination and calibration with 1,000 bootstraps. In summary, MCB patients had a better prognosis than IDC patients. Interestingly, unmarried status in addition to expected risk factors such as larger tumor size and increasing number of positive lymph nodes were found to worsen the BCSS of MCB. We also established a competing risk nomogram as an easy-to-use tool for prognostic estimation of MCB patients.

Fine-Needle Cytological Characteristics of Carcinoma Breast with Medullary or Medullary-like Features Masquerading as Dendritic Reticulum Cell Sarcoma: An Attempt to Explore the Reasons for Erroneous Cytologic Interpretation.

Background:Infiltration of tumors by dendritic reticulum cells (DRC) reflects the host immune defense mechanism. We observed three breast carcinomas cases with dense tumor-infiltrating DRC and lymphocytes in fine-needle aspiration (FNA) smears, leading to cytodiagnosis or differential diagnosis of dendritic reticulum cell sarcoma (DRCS). An attempt was made to find out the reason behind such an erroneous interpretation.Materials and Methods:Between 2009 and 2014, two cases were diagnosed as DRCS of the female breast by FNA cytology and in one case possibility of DRCS was considered along with medullary breast carcinoma (MBC). We compare and contrast the cytomorphological features of these three cases with those of nine cytologically diagnosed MBC.Results:Cases diagnosed as DRCS or MBC showed singly dispersed tumor cells, nuclear pleomorphism, bare nuclei, prominent nucleoli, and presence of lymphocytes. There was no significant difference between the two groups for discohesive clusters, syncytial clusters, plasma cells, neutrophils, foamy histiocytes, and necrosis. However, there was significant difference for presence of cohesive clusters (0% DRCS and 100% MBC, P = 0.00485), severe degree (+++) of pleomorphism (100% DRCS vs. 11.1% MBC, P = 0.01818), +++ DRC (P = 0.04697), and DRC with ++ to +++ enlarged nuclei (P = 0.03333), and pleomorphic nuclei (P = 0.00833). Two of the three cytologically diagnosed DRCS cases proved to be MBC or MBC-like and one as invasive ductal carcinoma. Six of nine cytologically diagnosed MBC cases with histology proved to be invasive breast carcinomas.Conclusion:Criteria for cytodiagnosis MBC need a fresh look. Cases with numerous dendritic cells possibly represent MBC.

Histopathological and immunohistochemical diagnosis of advanced medullary breast carcinoma: case report

Histopathological and immunohistochemical diagnosis of advanced medullary breast carcinoma: case report

Occult medullary breast carcinoma in a male

Occult medullary breast carcinoma in a male

Medullary Breast Carcinoma, a Triple-Negative Breast Cancer Associated with BCLG Overexpression

Medullary breast carcinoma (MBC) is a rare subtype of triple-negative breast cancer with specific genomic features within the spectrum of basal-like carcinoma (BLC). In this study of 19 MBCs and 36 non-MBC BLCs, we refined the transcriptomic and genomic knowledge about this entity. Unsupervised and supervised analysis of transcriptomic profiles confirmed that MBC clearly differs from non-MBC BLC, with 92 genes overexpressed and 154 genes underexpressed in MBC compared with non-MBC BLC. Immunity-related pathways are the most differentially represented pathways in MBC compared with non-MBC BLC. The proapoptotic gene BCLG (official name BCL2L14) is by far the most intensely overexpressed gene in MBC. A quantitative RT-PCR validation study conducted in 526 breast tumors corresponding to all molecular subtypes documented the specificity of BCLG overexpression in MBC, which was confirmed at the protein level by immunohistochemistry. We also found that most MBCs belong to the immunomodulatory triple-negative breast cancer subtype. Using pan-genomic analysis, it was found that MBC harbors more losses of heterozygosity than non-MBC BLC. These observations corroborate the notion that MBC remains a distinct entity that could benefit from specific treatment strategies (such as deescalation or targeted therapy) adapted to this rare tumor type.

Cellular Composition and Contribution of Tertiary Lymphoid Structures to Tumor Immune Infiltration and Modulation by Radiation Therapy.

Immune-based anti-cancer strategies combined with radiation therapy (RT) are actively being investigated but many questions remain, such as the ideal treatment scheme and whether a potent immune response can be generated both locally and systemically. In this context, tumor-associated tertiary lymphoid structures (TLS) have become a subject of research. While TLS are present in several types of cancer with strong similarities, they are especially relevant in medullary breast carcinoma (MBC). This suggests that MBC patients are ideally suited for investigating this question and may benefit from adapted therapeutic options. As RT is a corner-stone of MBC treatment, investigating interactions between RT and TLS composition is also clinically relevant. We thus first characterized the lymphoid structures associated with MBC in a patient case report and demonstrated that they closely resemble the TLS observed in a genetical mouse model. In this model, we quantitatively and qualitatively investigated the cellular composition of the tumor-associated TLS. Finally, we investigated TLS regulation after hypo-fractionated RT and showed that RT induced their acute and transient depletion, followed by a restoration phase. This study is the first work to bring a comprehensive and timely characterization of tumor-associated TLS in basal conditions and after RT. It highlights cellular targets (i.e., Tregs) that could be selectively modulated in subsequent studies to optimize anti-tumor immune response. The study of TLS modulation is worth further investigation in the context of RT and personalized medicine.

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis

BackgroundTriple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC. MethodsA total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan–Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome. ResultsMBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC. Conclusion(s)Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments.