Nomograms to predict the long-term prognosis for non-metastatic invasive lobular breast carcinoma: a population-based study
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ABSTRACT:
SUBMITTER: Guan Y
PROVIDER: S-EPMC11341842 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Invasive lobular carcinoma (ILC) is a common breast cancer subtype that is often diagnosed at advanced stages and causes significant morbidity. Late-onset secondary tumor recurrence affects up to 30% of ILC patients, posing a therapeutic challenge if resistance to systemic therapy develops. Nonetheless, there is a lack of preclinical models for ILC, and the current models do not accurately reproduce the complete range of the disease. We created clinically relevant metastatic xenografts to address this gap by grafting the triple-negative IPH-926 cell line into mouse milk ducts. The resulting intraductal xenografts accurately recapitulate lobular carcinoma in situ (LCIS), invasive lobular carcinoma, and metastatic ILC in relevant organs. Using a panel of 15 clinical markers, we characterized the intratumoral heterogeneity of primary and metastatic lesions. Interestingly, intraductal IPH-926 xenografts express low but actionable HER2 and are not dependent on supplementation with the ovarian hormone estradiol for their growth. This model provides a valuable tool to test the efficiency of potential new ILC therapeutics, and it may help detect vulnerabilities within ILC that can be exploited for therapeutic targeting.
| S-EPMC10340059 | biostudies-literature
Project description:BackgroundLimited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.MethodsWe retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.FindingsILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05).InterpretationEvaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.FundingLynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.
| S-EPMC9637866 | biostudies-literature
Project description:PurposeThe purpose of this study was to investigate the expression of PD-L1 in invasive lobular carcinoma (ILC) and to determine its implications.MethodsTissue microarrays were constructed for 101 cases of ILC, and immunohistochemical staining for PD-L1 (using 22C3, SP142, and SP263 antibodies) was performed to examine the correlation between staining results and clinicopathologic parameters.ResultsThe positive cut-off values were defined as tumor cell (TC)≥1%, immune cell (IC)>0%, and IC≥1%. The range of PD-L1 TC positivity was 0.0-2.0%, with PD-L1 SP263 TC showing the highest positivity of 2.0%. The range of PD-L1 IC positivity was 0-21.8% for IC ≥ 1%, with PD-L1 22C3 IC showing the highest positivity. When PD-L1 IC was positive (IC≥1%), the highest antibody agreement was observed between SP263 and SP142 (OA = 93.1%), while the lowest agreement was observed between 22C3 and SP263 (OA = 73.3%, κ = 0.040). PD-L1 22C3 IC positivity (≥1%) was associated with high nuclear grade (p = 0.002), HER-2 positivity (p = 0.019), and pleomorphic type (p = 0.002).ConclusionPD-L1 expression in ILC shows a low TC positivity rate (0-2%) with various antibody clones and a variable IC positivity rate (0-21.8%). Pleomorphic type ILC exhibits higher PD-L1 IC positivity.
| S-EPMC11466385 | biostudies-literature
Project description:Secondary bladder tumors are relatively rare among all bladder tumors, while bladder metastases from breast cancer have been rarely reported. Furthermore, signet-ring differentiation may appear in the metastases from a breast invasive lobular carcinoma regardless of whether the primary breast tumor had signet-ring cells, which may cause diagnostic uncertainty. We report a case of a 55-year-old female patient with diffuse bladder thickening as the chief complaint and no specific clinical manifestations. While the cystoscopy showed multiple scattered red protuberances, the biopsy suggested signet-ring-cell carcinoma. The gastroscopy results suggested poorly differentiated adenocarcinoma with signet-ring cells. Considering the patient's history of invasive lobular carcinoma of the breast, chronic myeloid leukemia, and metastatic endometrial carcinoma from the breast, we performed an immunohistochemical analysis and the results indicated that signet-ring-cell carcinomas of the stomach and bladder originated from the invasive lobular carcinoma of the breast. We performed positron emission tomography/computed tomography and the results showed that there were multiple bone metastases already present. This was the first English case report of invasive lobular carcinoma of the breast metastasizing to the uterus, stomach, bladder, and bones with multiple signet-ring-cell variations. This study shares our reasons for misdiagnosing and opinions on diagnosing and treating for this kind of cases.
| S-EPMC8888881 | biostudies-literature
Project description:Metastatic cancer to the female genital organs is a very rare clinical presentation. The myometrium is more frequently affected than the endometrium. Prolonged use of tamoxifen has been found to be associated with endometrial hyperplasia, endometrial polyp formation, and the development of endometrial adenocarcinoma in some cases. A 55-year-old lady with a history of invasive lobular carcinoma of the breast that had been operated upon with left mastectomy 7 years previously & who had also been treated with tamoxifen for 5 years presented with irregular vaginal bleeding and lower abdominal pain. The patient had a three cm uterine fibroid with an endometrial polyp. She had anemia with hemoglobin level 8 mg/dl. Laparoscopic hysterectomy with bilateral oophorectomy was performed for a polyp in the endometrium which proved to be a metastasis from her lobular carcinoma of the breast. Patients with breast cancer who present with abnormal vaginal bleeding should alert the physicians about the possibility of metastatic breast cancer to the uterus regardless the use of the hormonal therapy such as tamoxifen. The pathologists also should be aware of this possibility and they should examine the polyps very carefully to detect any metastatic foci especially if the patient has been treated with tamoxifen.
| S-EPMC7015833 | biostudies-literature
Project description:Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.
| S-EPMC7407940 | biostudies-literature
Project description:To investigate the usefulness of imaging features for differentiating between small lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC). It included 52 female with LCISs (median 45 years, range 32-67 years) and 180 female with ILCs (median 49 years, range 36-75 years), with the longest diameter of ≤ 2 cm, who were evaluated between January 2012 and December 2016. All the female underwent mammography and ultrasonography. Twenty female with LCIS and 150 female with ILC underwent MRI. The clinical and imaging features were compared, and multivariate analysis was performed to identify the independent predictors of LCIS. Female with LCIS were also subgrouped by lesion size and compared with the female with ILC. Multivariate analysis showed that younger age [odds ratio (OR) = 1.100], smaller lesion size (OR = 1.103), oval or round shape (OR = 4.098), parallel orientation (OR = 5.464), and isoechotexture (OR = 3.360) were significant independent factors predictive of LCIS. The area under the receiver operating characteristic curve for distinguishing LCIS from ILC was 0.904 (95% confidence interval, 0.857-0.951). Subgroup analysis showed that benign features were more prevalent in female with smaller LCISs (≤ 1 cm) than in those with ILC. Small LCISs tend to demonstrate more benign features than small ILCs. Several imaging features are independently predictive of LCIS.
| S-EPMC9432355 | biostudies-literature
Project description:ObjectivesThe present study aimed to develop and validate nomograms to predict the survival of patients with breast invasive micropapillary carcinoma (IMPC) to aid objective decision-making.DesignPrognostic factors were identified using Cox proportional hazards regression analyses and used to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) at 3 and 5 years. Kaplan-Meier analysis, calibration curves, the area under the curve (AUC) and the concordance index (C-index) evaluated the nomograms' performance. Decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system.SettingPatient data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. This database holds data related to the incidence of cancer acquired from 18 population-based cancer registries in the US.ParticipantsWe ruled out 1893 patients and allowed the incorporation of 1340 patients into the present study.ResultsThe C-index of the AJCC8 stage was lower than that of the OS nomogram (0.670 vs 0.766) and the OS nomograms had higher AUCs than the AJCC8 stage (3 years: 0.839 vs 0.735, 5 years: 0.787 vs 0.658). On calibration plots, the predicted and actual outcomes agreed well, and DCA revealed that the nomograms had better clinical utility compared with the conventional prognosis tool. In the training cohort, the NRI for OS was 0.227, and for BCSS was 0.182, while the IDI for OS was 0.070, and for BCSS was 0.078 (both p<0.001), confirming its accuracy. The Kaplan-Meier curves for nomogram-based risk stratification showed significant differences (p<0.001).ConclusionsThe nomograms showed excellent discrimination and clinical utility to predict OS and BCSS at 3 and 5 years, and could identify high-risk patients, thus providing IMPC patients with personalised treatment strategies.
| S-EPMC9944677 | biostudies-literature
Project description:BackgroundInvasive pleomorphic lobular carcinoma (PLC) of the breast is a subtype of invasive lobular cancer which compromises approximately 1% of all epithelial breast malignancies and is characterized by higher nuclear pleomorphism and poorer prognosis than classic invasive lobular cancer (ILC). Since PLC is more aggressive than classical ILC, we examined the underlying molecular alterations in this subtype of breast cancer to understand the possible benefit from targeted therapies.MethodsIn this study, we investigate the clinical characteristics and molecular alterations in 16 PLC from our institution. Additionally, we examined the clinical and genomic features in 31 PLC from the Cancer Genome Atlas (TCGA).ResultsOverall, our analysis of PLC found that 28% had activating ERBB2 mutations, 21% had ERBB2 amplification, and 49% activating PIK3CA mutations. Among cases from our institution, we found 19% with activating ERBB2 mutations, 25% had ERBB2 amplification, and 38% with activating PIK3CA mutations. In data from TCGA, 32% had activating ERBB2 mutations, 19% had ERBB2 amplification, and 55% had activating PIK3CA mutations. While classic ILC in TCGA had similar percentages of PIK3CA alterations compared to PLC, activating ERBB2 alterations were exceedingly rare, with no activating ERBB2 mutations and only one case with ERBB2 amplification. Interestingly, in further examining TCGA data which included FGFR1 and PTEN, 94% of PLC had alterations in ERBB2, FGFR1, or the PI3K pathway.ConclusionsOur results show a high frequency of ERBB2 and PIK3CA alterations in PLC and suggest all PLC should be tested for potential therapeutic targeting.
| S-EPMC7805167 | biostudies-literature
Project description:PurposeNomogram for predicting more than a 5-year survival for non-metastatic nasopharyngeal carcinoma (NPC) was lacking. This study aimed to develop the new nomograms to predict long-term survival in these patients.ResultsThe median follow-up time for training set and test set was 95.2 months and 133.3 months, respectively. The significant predictors for death were age, gender, body mass index (BMI), T stage, N stage, lactate dehydrogenase (LDH), and radiotherapy techniques. For predicting recurrence, age, gender, T stage, LDH, and radiotherapy techniques were significant predictors, whereas age, gender, BMI, T stage, N stage and LDH were significant predictors for distant metastasis. The calibration curves showed the good agreements between nomogram-predicted and actual survival. The c-indices for predicting death, recurrence, and distant metastases between nomograms and the TNM staging system were 0.767 VS.0.686 (P<0.001), 0.655 VS.0.585 (P<0.001), and 0.881 VS.0.754 (P<0.001), respectively. These results were further confirmed in the test set.MethodsOn the basis of a retrospective study of 1593 patients (training set) who received radiotherapy alone or concurrent chemoradiotherapy from 2000 to 2004, significant predictors were identified and incorporated to build the nomograms. The calibration curves of nomogram-predicted survival versus the actual survival were plotted and reviewed. Bootstrap validation was performed to calculate the concordance index (c-index). These models were further validated in an independent prospective trial (test set, n=400).ConclusionThe established nomograms suggest more-accurate long-term prediction for patients with non-metastatic NPC.
| S-EPMC5045427 | biostudies-literature