Variability in hospital treatment costs: a time-driven activity-based costing approach for early-stage invasive breast cancer patients

ObjectivesUsing a standardised diagnostic and generic treatment path for breast cancer, and the molecular subtype perspective, we aim to measure the impact of several patient and disease characteristics on the overall treatment cost for patients. Additionally, we aim to generate insights into the drivers of cost variability within one medical domain.Design, setting and participantsWe conducted a retrospective study at a breast clinic in Belgium. We used 14 anonymous patient files for conducting our analysis.ResultsSignificant cost variations within each molecular subtype and across molecular subtypes were found. For the luminal A classification, the cost differential amounts to roughly 166%, with the greatest treatment cost amounting to US$29 780 relative to US$11 208 for a patient requiring fewer medical activities. The major driver for these cost variations relates to disease characteristics. For the luminal B classification, a cost difference of roughly 242% exists due to both disease-related and patient-related factors. The average treatment cost for triple negative patients amounted to US$26 923, this is considered to be a more aggressive type of cancer. The overall cost for HER2-enriched is driven by the inclusion of Herceptin, thus this subtype is impacted by disease characteristics. Cost variability across molecular classifications is impacted by the severity of the disease, thus disease-related factors are the major drivers of cost.ConclusionsGiven the cost challenge in healthcare, the need for greater cost transparency has become imperative. Through our analysis, we generate initial insights into the drivers of cost variability for breast cancer. We found evidence that disease characteristics such as severity and more aggressive cancer forms such as HER2-enriched and triple negative have a significant impact on treatment cost across the different subtypes. Similarly, patient factors such as age and presence of gene mutation contribute to differences in treatment cost variability within molecular subtypes.

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Breast cancer in Angola, molecular subtypes: The first preliminary study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13075 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13075-e13075

Author(s):

Lúcio Lara Santos ◽

Fernando Miguel ◽

Lygia Vieira Lopes ◽

Julio Oliveira ◽

Eduardo Ferreira ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Locally Advanced ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Therapeutic Decisions ◽

Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

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Activation of epithelial-mesenchymal transition process during breast cancer progression – the impact of molecular subtype and stromal composition

Acta Biochimica Polonica ◽

10.18388/abp.2020_5719 ◽

2021 ◽

Author(s):

Aleksandra Markiewicz ◽

Justyna Topa ◽

Marta Popęda ◽

Jolanta Szade ◽

Jarosław Skokowski ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Ki 67 ◽

Mesenchymal Transition ◽

Metastatic Colonization ◽

The Impact

Breast cancer (BC) is a heterogeneous disease with different molecular subtypes, which can be defined by oestrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors’ status as luminal, HER2+ and triple negative (TNBC). Molecular subtypes also differ in their epithelial-mesenchymal phenotype, which might be related to their aggressiveness, as activation of the epithelial-mesenchymal transition (EMT) is linked with increased ability of cancer cells to survive and metastasize. Nevertheless, the reverse process of mesenchymal-epithelial transition was shown to be required to sustain metastatic colonization. In this study we aimed to analyse activation of the EMT process in primary tumours (PT), which have (N+) or have not (N–) colonized the lymph nodes, as well as the lymph nodes metastases (LNM) themselves in 88 BC patients. We showed that luminal N– PT have the lowest activation of the EMT process (27%), in comparison to N+ PT (48%, p=0.06). On the other hand, TNBC do not show statistically significant EMT activation at the stage before lymph colonization (N–, 83%) and after colonization of the lymph nodes (N+, 63%, p=0.58). TNBC are also the least plastic (unable to change the EMT phenotype) in terms of turning EMT on or off between matched PT and LNM (0% EMT plasticity in TNBC vs 36% plasticity in luminal tumours). Moreover, in TNBC activation of EMT was correlated with increased cell division rate of the PT– in mesenchymal TNBC PT median Ki-67 was 45% in comparison to 10% in epithelial TNBC PT (p=0.002), whereas in PT of luminal subtypes Ki-67 did not differ between epithelial and mesenchymal phenotypes. Profiling of immunotranscriptome of epithelial and mesenchymal luminal BC with Nanostring technology revealed that N– PT with epithelial phenotype were enriched in inflammatory response signatures, whereas N+ mesenchymal cancers showed elevated MHC class II antigen presentation. Overall, activation of EMT changes during cancer progression and metastatic colonization of the lymph nodes depending on the PT molecular subtype and is related to differences in stromal signatures. Activation of EMT is associated with colonizing phenotype in luminal PT and proliferative phenotype of TNBC.

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Molecular profiling of breast carcinoma with IHC surrogates in a tertiary care centre in South India

Biomedicine ◽

10.51248/.v41i1.537 ◽

2021 ◽

Vol 41 (1) ◽

pp. 75-81

Author(s):

N. Priyathersini ◽

J. Thanka ◽

B Jayashree

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Triple Negative ◽

Ductal Carcinoma ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Tertiary Care ◽

P Value ◽

Her2 Receptor ◽

Luminal A

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years. Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status. Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors. Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.

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Association between body mass index and pathologic complete response in different breast cancer molecular subtypes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12624 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12624-e12624

Author(s):

Bryan Vaca-Cartagena ◽

Andrea Becerril Gaitan ◽

Ana Sofia Ferrigno ◽

Alejandro Aranda-Gutierrez ◽

Fabio A. Gonzalez-Mondellini ◽

...

Keyword(s):

Public Health ◽

Breast Cancer ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Pathologic Complete Response ◽

Significant Proportion ◽

Complete Response ◽

Public Health Care ◽

Obese Patients ◽

The Impact

e12624 Background: Obesity (BMI ≥30 kg/m2) and breast cancer (BC) are two major public health concerns worldwide. Obesity has been linked with aggressive clinicopathological features and inferior survival rates in patients with BC, regardless of molecular subtype. In addition, obesity has been associated with decreased pathological complete response (pCR) rates in some BC cohorts. However, the impact of obesity on pCR rates in different BC molecular subtypes is still a subject of debate. This study aims to explore the impact of obesity on pCR rates in women with different BC subtypes in a public health-care center. Methods: Medical records of women diagnosed with primary BC between 2009 and 2020 in a center in Monterrey, Mexico were reviewed. Patients with stage II or III at diagnosis treated with neoadjuvant chemotherapy (NAC) were considered eligible. Associations between variables were examined using Fisher's exact test of independence, employing logistic regression to calculate odds ratios (OR) when appropriate. Results: A total of 559 patients with a median age at diagnosis of 48 years (range 25-85) were included. Patients were diagnosed with stages II (37%) and III (63%). The most common molecular subtype was HR+/HER2- (49%), followed by TNBC (25%), HR-/HER2+ (15%), and HR+/HER2+ (11%). Regarding BMI, a significant proportion of patients was either overweight (34%) or obese (47%). In this cohort, a total of 134 (24%) patients achieved pCR following NAC with anthracycline- and/or taxane-containing regimens. pCR rates by subtype were as follows: HR-/HER2+ (41%), TNBC (34%), HR+/HER2+ (31%), and HR+/HER2- (13%). A significant association between pCR rates and molecular subtype was found (p<0.001). Overall, obesity was not significantly associated with pCR rates. However, on a stratified analysis, obese patients with HR+/HER2+ tumors had significantly decreased pCR rates compared to their non-obese counterparts (OR=0.21; 95%CI 0.05-0.93; p=0.040). pCR rates according to molecular subtype and obesity status are shown in the table below. Conclusions: Obesity has an adverse influence on pCR rates in patients with HR+/HER2+ tumors. Given the endemic nature of obesity in several low- and middle-income countries, effective programs that focus on prevention, weight reduction strategies, and health promotion are warranted. Furthermore, women should be encouraged to improve their diet and engage in regular physical activity. Efforts to elucidate potential factors that underlie lower pCR rates in obese patients with certain BC subtypes are required. [Table: see text]

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Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer

Breast Disease ◽

10.3233/bd-219004 ◽

2021 ◽

pp. 1-5

Author(s):

M. Husni Cangara ◽

Upik A. Miskad ◽

Rina Masadah ◽

Berti J. Nelwan ◽

Syarifuddin Wahid

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Receptor Expression ◽

Luminal A ◽

Ki 67 ◽

Her 2 ◽

Hormone Receptor Expression

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

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Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology)

Breast Care ◽

10.1159/000448186 ◽

2016 ◽

Vol 11 (4) ◽

pp. 248-252 ◽

Cited By ~ 8

Author(s):

Muhammet A. Kaplan ◽

Ulku Y. Arslan ◽

Abdurrahman Işıkdogan ◽

Faysal Dane ◽

Berna Oksuzoglu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Breast Cancer Patients ◽

Luminal A ◽

Curative Surgery ◽

Luminal B ◽

Distant Relapse

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. Methods: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. Results: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.

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Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer

10.21203/rs.2.22855/v1 ◽

2020 ◽

Author(s):

Lee Cheng Phua ◽

Soo Chin Lee ◽

Kwong Ng ◽

Mohamed Ismail Abdul Aziz

Keyword(s):

Breast Cancer ◽

Cost Effectiveness ◽

Combination Therapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cost Effective ◽

System Perspective ◽

Scenario Analyses ◽

The Cost ◽

The Impact

Abstract Background The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective. Methods A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties. Results Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at $67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the combination therapy was unlikely to be cost-effective even under extremely favourable assumptions. Conclusions Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent a cost-effective use of healthcare resources for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.

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Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer

10.21203/rs.2.22855/v2 ◽

2020 ◽

Author(s):

Lee Cheng Phua ◽

Soo Chin Lee ◽

Kwong Ng ◽

Mohamed Ismail Abdul Aziz

Keyword(s):

Breast Cancer ◽

Cost Effectiveness ◽

Combination Therapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cost Effective ◽

System Perspective ◽

Scenario Analyses ◽

The Cost ◽

The Impact

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Unraveling Triple-Negative Breast Cancer Tumor Microenvironment Heterogeneity: Towards an Optimized Treatment Approach

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz208 ◽

2019 ◽

Vol 112 (7) ◽

pp. 708-719 ◽

Cited By ~ 9

Author(s):

Yacine Bareche ◽

Laurence Buisseret ◽

Tina Gruosso ◽

Edwina Girard ◽

David Venet ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Tumor Microenvironment ◽

Spatial Pattern ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Statistical Tests ◽

Copy Number Loss

Abstract Background Recent efforts of gene expression profiling analyses recognized at least four different triple-negative breast cancer (TNBC) molecular subtypes. However, little is known regarding their tumor microenvironment (TME) heterogeneity. Methods Here, we investigated TME heterogeneity within each TNBC molecular subtype, including immune infiltrate localization and composition together with expression of targetable immune pathways, using publicly available transcriptomic and genomic datasets from a large TNBC series totaling 1512 samples. Associations between molecular subtypes and specific features were assessed using logistic regression models. All statistical tests were two-sided. Results We demonstrated that each TNBC molecular subtype exhibits distinct TME profiles associated with specific immune, vascularization, stroma, and metabolism biological processes together with specific immune composition and localization. The immunomodulatory subtype was associated with the highest expression of adaptive immune-related gene signatures and a fully inflamed spatial pattern appearing to be the optimal candidate for immune check point inhibitors. In contrast, most mesenchymal stem-like and luminal androgen receptor tumors showed an immunosuppressive phenotype as witnessed by high expression levels of stromal signatures. Basal-like, luminal androgen receptor, and mesenchymal subtypes exhibited an immune cold phenotype associated with stromal and metabolism TME signatures and enriched in margin-restricted spatial pattern. Tumors with high chromosomal instability and copy number loss in the chromosome 5q and 15q regions, including genomic loss of major histocompatibility complex related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism. Conclusions Our results demonstrate that each TNBC subtype is associated with specific TME profiles, setting the ground for a rationale tailoring of immunotherapy in TNBC patients.

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Predicting the Incidence and Prognosis of Bone Metastatic Breast Cancer: A SEER-Based Observational Study

BioMed Research International ◽

10.1155/2020/1068202 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Dongning Shi ◽

Junwen Bai ◽

Yibo Chen ◽

Xia Wang ◽

Yafeng Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Large Population ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

The Impact

Background. To determinate the association relationship of breast cancer bone metastasis and cancer characteristics and molecular subtype. Furthermore, to evaluate the impact of molecular subtype on prevalence and prognosis of bone metastasis from the breast cancer base on a large population real-word program, the Surveillance, Epidemiology, and End Results (SEER) database. Methods. We collected and analyzed the data obtained from SEER, which showed molecular subtype information for each patient. The prevalence and outcome of bone metastasis in breast cancer were estimated as per the different molecular subtypes. Results. Occurrence of bone metastasis in conformity with four different molecular subtypes in all 42684 breast cancer patients was 6.2, 9.4, 7.9, and 6.4%, respectively. The most unfavorable subtype was the triple-negative breast cancer (TNBC), followed by the luminal A, luminal B, and HER2 subtypes (hazard ratio [HR] of luminal A compared with TNBC, 0.533, 95% confidence interval, 0.444–0.641; HR of luminal B, 0.482, 95% CI 0.419–0.555; HR of HER2 subtype, 0.542, 95% CI 0.484–0.608). Brain metastasis impacts overall survival (OS) ( p < 0.001 ) fundamentally, and visceral metastases also significantly decreased OS ( p < 0.001 ). Conclusion. Bone metastasis patients present a more favorable oncological survival consequence than other metastases, and the TNBC subtype with bone metastasis showed the poorest tumor outcome compared with the other three molecular subtypes.

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