Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Statistical methods in cancer research

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies.

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Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

Purpose: To compare the clinical features, natural history, and outcomes for women with “triple-negative” breast cancer with women with other types of breast cancer. Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women9s College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. Results: The median follow-up time of the 1,601 women was 8.1 years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P P Conclusions: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.

https://clincancerres.aacrjournals.org/content/clincanres/13/15/4429.full.pdf

Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence

Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1001389

Triple-negative breast cancer.


 Background: The EuroQol- 5 Dimension (EQ-5D) is a generic patient-reported outcome measure widely used to capture meaningful change in health-related quality of life between treatments to inform drug and health technology reimbursement decision making. The EQ-5D-5L (5 level) consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analogue scale (VAS). Each dimension has 5 levels, ranging from 1 “no problems” to 5 “extreme problems”, generating 3125 distinct health states (HS). The VAS score ranges from 0 (worst health imaginable) to 100 (best health imaginable). We used Canadian Index values to calculate community-weighted utility scores for 5 pre-defined breast cancer (BC) disease states.Methods: This cross-sectional study included adult women diagnosed with stage I to IV BC, who completed EQ-5D-5L, during outpatient clinic visits at two academic cancer centres in Toronto. Participants were classified into 5 disease states, considered relevant both to clinical practice and economic modeling, ranging from primary breast cancer to metastatic disease. EQ-5D-5L scores were described for each disease state, and mean utility scores and VAS scores were calculated.Results: 549 women were included; the mean age was 57 (SD 12) years; 72% had a Charlson Comorbidity Index of 0. A majority reported “Slight” to “Moderate” problems for the “Pain/Discomfort” (60%) and “Anxiety/Depression” (55%) dimensions of EQ-5D-5L; in all other dimensions, most patients reported “No problems”. As expected, patients with metastatic BC had the highest proportion of reported problems. The mean EQ-5D-5L index score was 0.83 (SD 0.13; range 0.36 to 0.95), with a distribution skewed towards full health and a ceiling effect of 20% (n=110; Table 1). Only 126 different self-reported health states were observed in our patient population. Mean VAS was 75 (SD 17.5; range 10 to 100). For early BC, mean index scores were: 0.87 (n=49; SD 0.07) for patients on chemotherapy (+/-targeted therapy); 0.85 (n=212; SD 0.12) for patients on endocrine treatment (+/-targeted therapy); 0.79 (n=16; SD 16) for patients on targeted therapy; and 0.84 (n=129; SD 0.14) for patients not receiving systemic therapy. For metastatic BC, mean index scores were: 0.79 (n=36, SD 14) for patients on chemotherapy (+/-targeted therapy); 0.80 (n=79, SD 0.14) for patients on endocrine treatment (+/-targeted therapy); 0.69 (n=8; SD 0.19) for patients on targeted therapy; and 0.77 (n=20; SD 0.14) for patients not receiving systemic therapy.Conclusions: BC had an impact mainly in the “Pain/Discomfort” and “Anxiety/Depression” dimensions of EQ-5D-5L. A high ceiling effect was observed in this patient population, despite using the 5L version of EQ-5D. EQ-5D-5L health utilities were significantly lower for metastatic BC, but no significant differences were found among various early-stage BC states.
 Table 1.- Mean EQ-5D-5L Index and VAS scoresEQ-5D-5LIndex ScoresVASDisease StateN (%)Mean (SD)Min-MaxMean (SD)Min-Max1st year after primary BC146 (27)0.85 (0.12)*0.23-0.9576.5(16.6)10-1001st year after recurrence or primary BC13 (2)0.78 (0.21)0.13-0.9568.9(23.3)20-1002nd-5th year after a primary BC or recurrence treated with curative intent185 (34)0.84 (0.11)*0.21-0.9578.3(14.7)36-1006th and following years after a primary BC or recurrence treated with curative intent62 (11)0.86 (0.14)*0.36-0.9581.0(15.6)20-100Metastatic BC143 (26)0.78 (0.14)0.29-0.9567.3(19.2)21-100Total549 (100)0.83 (0.13)0.13-0.9575.0(17.5)10-100*significant difference was found between these disease states and metastatic diseases (P < 0.05).
 Citation Format: Sofia Torres, Ahmed Bayoumi, Maureen Trudeau, Ana Beatriz Kinupe Abrahao, Nicholas Mitsakakis, Murray Krahn, Geoffrey Liu. Eq-5d-5l utility scores for patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-11.

Abstract P4-12-11: Eq-5d-5l utility scores for patients with breast cancer

SUMMARY Background: Lung cancer (LC) is a leading cause of morbidity and mortality and there is limited information on the type, quantity and cost of home care services (HCS) for LC. Aim: The objectives of this study include: identifying a stage IV LC cohort; determining the utilization and costs of HCS for the stage IV LC cohort; and comparing HCS utilization and costs by phase of disease. Methods: New cases of stage IV LC were extracted from a provincial cancer registry and linked to administrative datasets. HCS utilization and costs (2009 Canadian dollars [CAD]) for stage IV cases were determined from a public payer perspective and by disease phase. Results: There are 4616 stage IV LC patients who used HCS.. The mean number of HCS visits per 30 days was 7.7 and the mean cost per 30 days was CAD$798 for terminal-phase patients. Conclusion: HCS costs for stage IV patients are less expensive than other health resources.

Home care utilization and costs in stage IV lung cancer: a Canadian public payer experience

Purpose: Premenopausal women with breast cancer often enter a premature menopause during initial treatment of their malignancy, with resulting loss of childbearing capacity, onset of menopausal symptoms, and subsequent prolonged exposure to long-term risks of menopause. Adjuvant therapy is believed to contribute to this early menopause. Patients and Methods: One hundred eighty-three premenopausal women with locoregional breast cancer (tumor-node-metastasis staging system classification, T1-3 N0-1 M0) who had undergone surgical treatment and provided information on menopausal status at diagnosis and 1 year later were enrolled. Systemic adjuvant therapy was recorded. Univariate and multivariate predictors of menopause were examined. Results: Age, weight gain, tumor stage, nodal stage, and systemic adjuvant therapy (chemotherapy, tamoxifen) were all significant univariate correlates of menopause. In multivariate analysis, age, chemotherapy, and hormone therapy (tamoxifen) made significant independent contributions to the onset of menopause. Conclusion: Age and systemic chemotherapy are the strongest predictors of menopause in women with locoregional breast cancer. They independently contributetomenopause.Agraphicrepresentationofourmultivariate model allows an estimation of risk of menopause according to patient age and planned adjuvant treatment, and it may facilitate clinical decision-making. J Clin Oncol 17:2365-2370. r 1999 by American Society of Clinical Oncology.

Risk o f M enopause D uring t he F irst Y ear A fter B reast Cancer D iagnosis


 Background: The EuroQol- 5 Dimension (EQ-5D) is a generic patient-reported outcome measure widely used to capture meaningful change in health-related quality of life between treatments to inform drug and health technology reimbursement decision making. We investigated the construct validity of EQ-5D-5L in women with breast cancer.
 Methods: This study included adult women diagnosed with stage I to IV breast cancer, who completed the EQ-5D-5L and the Edmonton Symptom Assessment System (ESAS) during outpatient clinic visits at two academic cancer centres in Toronto. We evaluated construct validity through assessing known-group validity and convergent/divergent validity. For known-group validity, the primary analysis tested the hypothesis that EQ-5D-5L could adequately discriminate between patients with metastatic disease and early-stage disease; secondary analyses addressed utility values between women in breast-cancer associated health states. A suggested minimally important difference (MID) for the Canadian scoring of the EQ-5D-5L is 0.037; we evaluated whether the lower bound of the 95% confidence interval (95%CI) exceeded this value. In terms of convergent/divergent validity, the primary analysis tested the hypothesis that EQ-5D-5L mean utility values for each health state (HS) would be at least moderately correlated with ESAS total symptom distress score (SDS) (|r|>0.30) using Wilcoxon rank-sum tests and Spearman’s correlation tests. Construct validity was considered as acceptable if the hypotheses of the primary analysis are satisfied.
 Results: We recruited 549 women, 406 (74%) with early-stage disease and 143 (26%) with metastatic disease (HS5), with a mean age of 57 (SD 12); 412 (75%) had been diagnosed with breast cancer in the 7 years prior to recruitment and were receiving active treatment for their cancer. The mean utility value for early-stage breast cancer was 0.84 (95% CI 0.83-0.86) and for metastatic breast cancer (0.78, 95% CI 0.76-0.81). This difference was 0.060 (95% CI 0.036 to 0.085, p< 0.001) with the lower bound of the confidence interval slightly less than the prespecified MID (0.037). There was no significant difference between the mean utility value for women in the first year after primary breast cancer diagnosis (HS1), and women in their second to fifth year after a primary breast cancer treated with curative intent (HS3) or between women in HS1 and women in their sixth and following years after a primary breast cancer treated with curative intent (HS4). EQ-5D-5L also did not discriminate between women in HS3 and HS4. For convergent/divergent validity, there was a negative correlation between utility values and ESAS physical, emotional and total SDSs. EQ-5D-5L and ESAS total SDSs correlation coefficients were higher than 0.30 for all health states.
 Conclusion: EQ-5D-5L met criteria for convergent/divergent validity in women with breast cancer. The tests for discriminant validity were equivocal, suggesting more research is needed for assessing construct validity with a larger sample size.
 Table 1. EQ-5D-5L Utility Values. N= number; Std Dev= standard deviation; IQR= interquartile range; CI= confidence interval
 Citation Format: Sofia Torres, Maureen Trudeau, Geoffrey Liu, Nicholas Mitsakakis, Ahmed Bayoumi. Validity of EQ-5D-5L for women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-43.

Abstract P6-05-43: Validity of EQ-5D-5L for women with breast cancer

Le traitement du cancer du sein souleve des preoccupations precises qui sont uniques aux besoins des patientes plus âgees. Bien que le traitement du cancer du sein au stade precoce de la maladie ne varie que tres peu avec l’âge, la prise en charge optimale des patientes plus âgees atteintes de cette maladie exige souvent des soins de soutien interdisciplinaires complexes en raison des multiples comorbidites. Le present article fait le point sur la conduite therapeutique optimale pour le cancer du sein chez les femmes de 65 ans et plus dans une perspective interdisciplinaire. Une recension des ecrits concernant la prise en charge des patientes plus âgees atteintes d’un cancer du sein a ete effectuee dans les bases de donnees MEDLINE et EMBASE. Le point de vue de plusieurs specialites a ete retenu : geriatrie, radio-oncologie, oncologie medicale, oncologie chirurgicale, psycho-oncologie, soins palliatifs, soins infirmiers et travail social. Ce groupe de patientes necessite une collaboration interprofessionnelle des le diagnostic puis pour toute la duree du traitement, jusqu’a la periode de retablissement. Par consequent, nous recommandons un programme interdisciplinaire specifique au traitement des patientes plus âgees atteintes d’un cancer du sein pour l’optimisation de leurs soins de sante. Mots-cles : cancer du sein; femmes plus âgees; multidisciplinaire; traitement du cancer du sein

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Maureen E. Trudeau

Papers

Abstract P4-12-11: Eq-5d-5l utility scores for patients with breast cancer

Home care utilization and costs in stage IV lung cancer: a Canadian public payer experience

Risk o f M enopause D uring t he F irst Y ear A fter B reast Cancer D iagnosis

Abstract P6-05-43: Validity of EQ-5D-5L for women with breast cancer

Vers une approche multidisciplinaire optimale du traitement du cancer du sein chez les patientes plus âgées