Bronchoalveolar carcinoma as an unsuspected cause for worsening shortness of breath in a patient with metastatic breast cancer

A 70-year-old woman with lung metastases from a breast cancer presented with worsening cough and dyspnoea. She recently had a pleurodesis for a malignant pleural effusion. Chest CT scans demonstrated various radiological changes leading to diagnostic challenges. Differential diagnoses included empyema, pleural disease progression, pulmonary oedema, pneumonitis, lymphangitis and atypical infections. She deteriorated despite a multimodality treatment strategy. Postmortem examination confirmed that lung changes were consistent with a bronchoalveolar carcinoma unrelated to the known metastatic breast cancer. The eventual knowledge of this diagnosis was reassuring to the treating medical team and a comfort to the relatives who witnessed the lack of response to standard treatment.

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Effect of additional administration of pertuzumab for the post-treatment in patients with HER2-positive locally advanced/metastatic breast cancer who were previously treated with pertuzumab.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12500 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12500-e12500

Author(s):

Shinichiro Kubo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Anticancer Agents ◽

Clinical Benefit ◽

Standard Treatment ◽

Locally Advanced ◽

Metastatic Breast ◽

Her2 Positive ◽

Intervention Treatment ◽

Previously Treated

e12500 Background: Currently, there are no data related to re-administering trastuzumab (T) + pertuzumab (P) beyond the second-line therapy to patients with human epidermal growth factor receptor 2-positive advanced/metastatic breast cancer (HER2-MBC) who had previously received P. The present study targeted patients with HER2-MBC who were previously treated with P and aimed to evaluate the efficacy and safety of additional administration (top-up intervention) of P post-disease progression (PD) after standard treatment with T plus chemotherapy vinorerbine(VNR) or eribulin (ERI). Methods: SBP-08 was a multicenter, collaborative, single-arm phase II study of HER2-MBC patients who had previously received P. After standard treatment with T and chemotherapy, P was additionally administered (top-up intervention) post-PD. Results: Eleven HER2-MBC patients, recruited between June 2016 and June 2018, who had previously received P participated in this study. Their mean age was 63.5 years, and 45% were estrogen receptor (ER)-negative, while 55% were ER-positive. The mean chemotherapy history was 3.6 regimens, with a median of four regimens. Previous treatment regimens with P had been effective in all patients. All patients had organ metastasis and treatment histories with TDM-1. Initially, during the two-year case collection period, registration of 30 patients was planned. However, the study was terminated because the interim analysis did not demonstrative effectiveness, and it was decided that there were no potential benefits to the patients. The overall response rate (ORR) of the standard treatment was 0%, stable disease (SD) was 36%, PD was 55%, and the clinical benefit rate (CBR) was 0%. The following combination anticancer agents were used: VNR (10 patients) and ERI (one patient). The intervention treatment (top-up with P) achieved the following: ORR 0%, SD 22%, PD 78%, and CBR 0%. PFS for the standard treatment was 1.6 months, whereas PFS for the intervention treatment was 1.3 months. In the standard treatment, febrile neutropenia was observed in two patients. No increases in adverse events were observed with the intervention treatment. Conclusions: No clinical benefit was demonstrated with the intervention treatment in the present study. Top-up with P after standard treatment with T and chemotherapy post-PD was deemed ineffective. Clinical trial information: UMIN000020837.

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Site-specific expression of amine oxidases in breast cancer metastases

Tumor Biology ◽

10.1177/1010428318776822 ◽

2018 ◽

Vol 40 (5) ◽

pp. 101042831877682 ◽

Cited By ~ 3

Author(s):

Yoon Jin Cha ◽

Woo Hee Jung ◽

Ja Seung Koo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Monoamine Oxidase ◽

Diamine Oxidase ◽

Amine Oxidase ◽

Lung Metastases ◽

Lysyl Oxidase ◽

Metastatic Breast ◽

Monoamine Oxidase B ◽

Related Proteins

We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0.001), tumoral diamine oxidase ( p = 0.003), stromal diamine oxidase ( p = 0.047), and stromal monoamine oxidase B ( p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity ( p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity ( p = 0.003) and the luminal A subtype ( p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity ( p = 0.008), especially in lung metastases ( p = 0.025), and stromal monoamine oxidase B positivity ( p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649–10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.

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A phase II study of docetaxel-carboplatin as first line therapy in the patients with visceral metastatic breast cancer: A Bangladesh experience

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10792 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10792-10792

Author(s):

M. S. Reza ◽

Q. Chowdhury ◽

M. A. Hai ◽

M. A. Rahman

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Phase Ii Study ◽

Lung Metastases ◽

Performance Status ◽

Hepatic Metastases ◽

Metastatic Breast ◽

Breast Cancer Patients

10792 Background: Metastatic breast cancer is heterogeneous and treatment decisions are influenced by multiple factors. Docetaxel remains as the standard chemotherapy agent in the management of metastatic breast cancer. We conducted a phase II study to examine the efficacy and tolerability of docetaxel with carboplatin in the treatment of visceral metastatic breast cancer patients. Methods: From July 2000 to December 2004, 32 patients with; histologically/cytologically proven, bidimensionally measurable visceral (pulmonary & hepatic) metastatic breast cancer, age 18–75 years with ECOG performance status 0–3, no prior chemotherapy, life expectancy > 3 months, adequate bone marrow, renal, hepatic and hematological values were enrolled. It was an open-labeled, non-randomized, single-centered and prospective study. The patients received docetaxel (75 mg/m2) and carboplatin AUC 5 on day 1 at an interval of 3 weeks. Outcome measures were response rates and tolerability was measured by adverse events and laboratory blood values. Results: This study consisted of 30 female and only 2 male patients. Median age was 55 years. 18 patients (56.25%) were presented with pulmonary metastases, where as there were 12 patients (66.67%) with single lung and the remaining 6 patients (33.34%) with bilateral lung metastases.14 patients (43.75%) had hepatic metastases. In total, 168 cycles chemotherapy were administered with a median of 5.25 cycles per patient, and 29/32 patients were evaluable for responses. The overall response was 62.07% with 8 complete responses and 10 partial responses. 6 patients (20.69%) had stable disease and only 5 patients (17.24%) had progressive disease. Grade 3 hematological toxicities were observed as follows: neutropenia (24%) and anemia (15.6%). Some non-hematological toxicities (including nausea, vomiting, fluid retention and peripheral neuropathy) in 15 patients (51.72%) were observed. No severe febrile neutropenia and no fatal events were observed. Conclusions: This phase II study supports the use of docetaxel-carboplatin combination in chemo naïve visceral metastatic breast cancer patients due to its very promising effects with well tolerated toxicities in Bangladeshi population. No significant financial relationships to disclose.

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DETECT III: A multicenter, randomized, phase III study to compare standard therapy alone versus standard therapy plus lapatinib in patients (pts) with initially HER2-negative metastatic breast cancer but with HER2-positive circulating tumor cells (CTC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.tps1146 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. TPS1146-TPS1146

Author(s):

Carsten Hagenbeck ◽

Carola Anna Melcher ◽

Johann Wolfgang Janni ◽

Andreas Schneeweiss ◽

Peter A. Fasching ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Targeted Therapy ◽

Clinical Benefit ◽

Standard Treatment ◽

Metastatic Breast ◽

Phase Iii ◽

Her2 Status ◽

Her2 Positive ◽

Phase Iii Study

TPS1146 Background: HER2 status may change over the course of disease in breast cancer pts. Approx. 20-30% of pts with initially HER2-negative breast cancer have HER2-positive metastasis (Zidan et al. 2005; Tewes et al. 2009). Determining HER2 status on CTC is one option to re-evaluate HER2 status at the time metastasis is diagnosed. Currently it is unclear if HER2-targeted therapy based on the assessment of HER2 status of CTC reveals a clinical benefit. Methods: This is a randomized, open-label, two arm phase III study to investigate the clinical efficacy of lapatinib, as a HER2-targeted therapy in initially HER2-negative metastatic breast cancer pts with HER2-positive CTC at the time of distant disease. As only half of the pts with HER2-negative metastatic breast cancer show CTC-positivity and of those approx. 32% will exhibit HER2-positive CTC (Fehm et al. 2010), screening of about 1420 pts is required to enroll 228 pts. Main inclusion criteria: metastatic breast cancer with HER2-negative primary tumor tissue and/or biopsies from metastatic sites or locoregional recurrences, evidence of ≥1 HER2-positive CTC and ≥1 measurable metastatic lesion according to RECIST. Eligible pts will be randomized 1:1 to receive standard treatment vs. standard treatment plus lapatinib. Standard chemo- or endocrine therapy must be approved in combination with lapatinib or been investigated in prior clinical trials. Primary endpoint is progression free survival. Secondary endpoints include overall response rate, clinical benefit rate, overall survival and dynamic of CTC. The DETECT III trial is one of the first trials where treatment is based on phenotypic characteristics of CTC. If this trial succeeds in proving efficacy of lapatinib in pts with initially HER2-negative metastatic breast cancer but HER2-positive CTC, this will establish a new strategy in the treatment of metastatic breast cancer.

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Evaluation of oral S-1 as a first-line chemotherapy for metastatic HER2-negative breast cancer: An analysis of two randomized phase III studies (SELECT BC-CONFIRM and SELECT BC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1083 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1083-1083

Author(s):

Reiki Nishimura ◽

Hirofumi Mukai ◽

Yukari Uemura ◽

Hiromitsu Akabane ◽

Youngjin Park ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Group ◽

Adverse Events ◽

Standard Treatment ◽

Metastatic Breast ◽

Phase Iii ◽

First Line ◽

Standard Treatment Group ◽

Line Chemotherapy

1083 Background: Anthracycline regimens and taxane have been first line chemotherapeutic options for HER2 negative metastatic breast cancer. In a previous phase III trial (SELECT BC), non-inferiority of S-1 was demonstrated in terms of overall survival (OS). The SELECT BC-CONFIRM study was designed to confirm the results of the SELECT BC study and to combine the two randomized studies. Methods: Patients (n = 618) in the first trial were randomly assigned (1:1) to the S-1 group or the taxane group. Patients (n = 230) in the second trial (SELECT BC-CONFIRM) were randomly assigned to the anthracycline group or the S-1 group. Treatment continued until tumor progression, unacceptable toxic effects, or completion of six courses in the standard regimen group and four courses in the S-1 group. The primary endpoint was OS and secondary endpoints were progression-free survival (PFS), time to treatment failure, adverse events, HRQOL and cost-effectiveness. A pooled analysis of the two studies was predefined to confirm the results of the SELECT BC study. Results: 1. The HR for the anthracycline group was 1.09 [95%CI 0.80-1.48] in SELECT BC-CONFIRM, and the estimated predictive posterior probability that the HR does not exceed the threshold 1.333 was 90.27%. 2. Median OS was 32.7 months (S-1 group) and 36.3 months (standard treatment group). S-1 was not inferior to standard treatment in terms of OS (p non-inferiority = 0.0062). Median PFS was 11.2 months (S-1 group) and 11.2 months (standard treatment group). 3. Treatment was discontinued due to adverse events (i.e., neutropenia, febrile neutropenia, fatigue and edema) in 5.7% in the S-1 group and 6.6% in the standard treatment group 4. The EORTC QLQ-C30 questionnaire (global health status) revealed that there was no difference between the S-1 and anthracycline groups (p = 0.257), but there was a significant difference between the S-1 and taxane groups (p = 0.0039). Conclusions: S-1 is not inferior to taxane or anthracycline with respect to OS as a first-line treatment for MBC. S-1 should be considered a new option as a first-line chemotherapy for HER2-negative metastatic breast cancer patients. Clinical trial information: UMIN000005449.

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TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

Journal of Oncology ◽

10.1155/2018/4793498 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Marwa H. Elnagdy ◽

Omar Farouk ◽

Amal K. Seleem ◽

Hoda A. Nada

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Cancer Metastasis ◽

Lung Metastases ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Significant Difference ◽

High Level

Introduction. Breast cancer metastasis occurs when tumor cells dissociate from the primary tumor and migrate to distant organs through the peripheral bloodstream or lymphatic drainage. Circulating tumor cells (CTCs) originate from primary sites or metastases and circulate in the patients’ bloodstream. Molecular assays for the detection and molecular characterization of CTCs can serve as a liquid biopsy and can represent an alternative to invasive biopsies as a source of tumor tissue in the metastatic patients.Patients and Methods. We analyzed the presence of CTCs in the peripheral blood of 50 breast cancer patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) to detecttrefoil factor family(TFF)1and3genes.Results. We found significant difference in the level of bothTFF1andTFF3mRNA in the blood of nonmetastatic versus metastatic breast cancer patients (p=0.001 and p= 0.038, respectively).TFF1mRNA was detected at higher levels in 34.6% of metastatic breast cancer patients as compared to 0% of nonmetastatic (p= 0.002). As regardsTFF3mRNA, it was detected at higher levels in 46.2% of metastatic breast cancer patients as compared to 4% of nonmetastatic (p= 0.026). Moreover, we found that the high level of bothTFF1andTFF3mRNA was related to estrogen status of the patients. The detection of high level ofTFF1mRNA in CTCs was associated with bone metastases (77.8%), while that ofTFF3was related to lymph node involvement (75%) and lung metastases (68.8%).Conclusion. The combined measurement of bothTFF1andTFF3mRNA level for differentiation of metastatic from nonmetastatic breast cancer gave 57.69% sensitivity and 83.3% specificity.

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Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin, gemcitabine, or capecitabine

Breast Cancer Research and Treatment ◽

10.1007/s10549-020-05867-0 ◽

2020 ◽

Vol 184 (2) ◽

pp. 559-565

Author(s):

Shayma Kazmi ◽

Debanjana Chatterjee ◽

Dheeraj Raju ◽

Rob Hauser ◽

Peter A. Kaufman

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Liver Metastases ◽

Real World ◽

Lung Metastases ◽

Metastatic Breast ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line

Abstract Purpose The purpose of this study was to estimate the overall survival (OS) in real-world clinical practice in patients with metastatic breast cancer (MBC) and visceral metastases (liver or lung) treated in the third-line setting with eribulin, gemcitabine or capecitabine overall and in the major clinical categories of MBC (TNBC, HR+/HER2−, and HER2+). Methods A retrospective, observational study was conducted with de-identified patient electronic health records from the Cancer Treatment Centers of America (CTCA). Patients with a diagnosis of metastatic breast with lung or liver metastases, and treated with eribulin, gemcitabine, or capecitabine as third-line therapy were included in the analysis. Landmark survival was calculated as percentage of patients alive at 6, 12, 24, and 36 months. Overall survival was compared between treatment arms within TNBC and HR+/HER2− using log-rank analysis. Cox regression analyses was performed to estimate hazard ratios for comparison of treatments within TNBC and HR+/HER2− subtype. Results 443 patients with liver or lung metastases received third-line therapy with eribulin (n = 229), gemcitabine (n = 134), or capecitabine (n = 80). Eribulin patients had a higher percentage of patients alive at all landmark timepoints vs. gemcitabine, and a higher percentage of patients alive until 36 months vs. capecitabine. Median survival times showed that overall, and within the TNBC and HR+/HER2− subtype, patients receiving eribulin had a numerically higher median overall survival. Conclusions This real-world evidence study is consistent with randomized clinical trial data and demonstrates consistency of eribulin effectiveness in MBC patients with lung or liver metastases overall and in TNBC and HR+/HER2− disease.

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Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

Acta Pharmaceutica ◽

10.1515/acph-2015-0002 ◽

2015 ◽

Vol 65 (1) ◽

pp. 53-63 ◽

Cited By ~ 5

Author(s):

Lulzime Ballazhi ◽

Emil Popovski ◽

Ahmed Jashari ◽

Faik Imeri ◽

Ibrahim Ibrahimi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cell Lines ◽

Anticancer Agents ◽

Lung Metastases ◽

Metastatic Breast ◽

Antiproliferative Effect ◽

Breast Cancer Cell Lines ◽

Thiazole Ring ◽

Diphenyltetrazolium Bromide

Abstract The study highlights the current progress in the development of coumarin scaffolds for drug discovery as novel anticancer agents in metastatic breast cancer. Eight compounds, combining the coumarin core and five membered heterocycles (isoxazoles and thiazoles) in hydrazinyldiene- -chroman-2,4-diones, were characterized in terms of a potential antiproliferative effect on bone (SCP1833) and lung (SCP4175) metastatic breast cancer cell lines using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell viability was evaluated after 48 and 72 h of treatment and the 50 % inhibitory concentrations were determined. The results demonstrated dose- and time-dependent activity, with the most potent molecules having a thiazole moiety, without or with additional methyl group(s) attached to the carbon(s) at position(s) 5 and/or 4 in the thiazole ring. These molecules possessed significantly higher potency against both test cell lines compared to 4-hydroxycoumarin

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Prognostic factors and survival outcomes according to tumor subtype in patients with breast cancer lung metastases

PeerJ ◽

10.7717/peerj.8298 ◽

2019 ◽

Vol 7 ◽

pp. e8298

Author(s):

Siying Chen ◽

Jin Yang ◽

Yang Liu ◽

Haisheng You ◽

Yalin Dong ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Cox Regression ◽

Lung Metastases ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Metastatic Sites

Background Reports on the incidence and prognoses of lung metastases when diagnosing breast cancer patients with different subtypes are limited. Our study investigated the effect of molecular sub-typing stratification on the prognoses of lung metastatic breast caner patients. Methods Patients with breast cancer and lung metastases were identified from Surveillance, Epidemiology and End Results population-based data between 2010 and 2015. Univariate and multivariate Cox regression analyses were performed to identify risk factors and prognoses, overall survival (OS) and breast cancer-specific survival for patients with breast cancer lung metastases. Results We identified 6,516 patients with lung metastatic breast cancer, representing 1.7% of the entire cohort and 30.4% of the subset with metastatic disease. This included 2,940 hormone receptor (HR)+/HER2− patients, 852 HR+/HER2+ patients, 547 HR−/HER2+ patients and 983 triple-negative patients. The median OS for all lung metastatic patients was 13 months. Multivariate analysis revealed that those lung metastatic breast cancer patients of older age (>80), black race, with poorly differentiated tumors, carcinoma histology, triple-negative subtype, more metastatic sites and no surgery, and no chemotherapy showed significantly poor survival, both overall and breast cancer-specific. Conclusions Our findings show that molecular sub-type and more metastatic sites might have significant influence on the incidence and prognosis of breast cancer lung metastases. We also identified several prognostic factors that could guide therapy selection in the treatment of lung metastatic patients.

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Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population

BMC Cancer ◽

10.1186/s12885-021-09038-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shaoyan Lin ◽

Hongnan Mo ◽

Yiqun Li ◽

Xiuwen Guan ◽

Yimeng Chen ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Triple Negative ◽

Lung Metastases ◽

Metastatic Breast ◽

Clinicopathological Characteristics ◽

Initial Diagnosis ◽

Survival Outcomes ◽

Han Population ◽

Triple Negative Subtype

Abstract Background We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population. Methods We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses. Results Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients. Conclusions Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.

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