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Showing papers by "Nehmat Houssami published in 2018"


Journal ArticleDOI
TL;DR: The study of radiomics in BC patients is a new and emerging translational research topic and high-quality prospective and reproducible studies are needed to further potential application.
Abstract: To perform a rapid review of the recent literature on radiomics and breast cancer (BC). A rapid review, a streamlined approach to systematically identify and summarize emerging studies was done (updated 27 September 2017). Clinical studies eligible for inclusion were those that evaluated BC using a radiomics approach and provided data on BC diagnosis (detection or characterization) or BC prognosis (response to therapy, morbidity, mortality), or provided data on technical challenges (software application: open source, repeatability of results). Descriptive statistics, results, and radiomics quality score (RQS) are presented. N = 17 retrospective studies, all published after 2015, provided BC-related radiomics data on 3928 patients evaluated with a radiomics approach. Most studies were done for diagnosis and/or characterization (65%, 11/17) or to aid in prognosis (41%, 7/17). The mean number of radiomics features considered was 100. Mean RQS score was 11.88 ± 5.8 (maximum value 36). The RQS criteria related to validation, gold standard, potential clinical utility, cost analysis, and open science data had the lowest scores. The majority of studies n = 16/17 (94%) provided correlation with histological outcomes and staging variables or biomarkers. Only 4/17 (23%) studies provided evidence of correlation with genomic data. Magnetic resonance imaging (MRI) was used in most studies n = 14/17 (82%); however, ultrasound (US), mammography, or positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-d-glucose integrated with computed tomography (18F FDG PET/CT) was also used. Much heterogeneity was found for software usage. The study of radiomics in BC patients is a new and emerging translational research topic. Radiomics in BC is frequently done to potentially improve diagnosis and characterization, mostly using MRI. Substantial quality limitations were found; high-quality prospective and reproducible studies are needed to further potential application.

178 citations


Journal ArticleDOI
TL;DR: Tomosynthesis improves CDR and reduces recall; however, effects are dependent on screening setting, with greater improvement in CDR in European/Scandinavian studies (biennial screening) and reduction in recall in US studies with high baseline recall.
Abstract: Background Tomosynthesis approximates a 3D mammogram of the breast, reducing parenchymal overlap that masks cancers or creates false "lesions" on 2D mammography, and potentially enabling more accurate detection of breast cancer. We compared breast cancer screening detection and recall in asymptomatic women for tomosynthesis vs 2D mammography. Methods A systematic review and random effects meta-analysis were undertaken. Electronic databases (2009-July 2017) were searched for studies comparing tomosynthesis and 2D mammography in asymptomatic women who attended population breast cancer screening and reporting cancer detection rate (CDR) and recall rate. All statistical tests were two-sided. Results Seventeen studies (1 009 790 participants) were included from 413 citations. The pooled incremental CDR for tomosynthesis was 1.6 cancers per 1000 screens (95% confidence interval [CI] = 1.1 to 2.0, P < .001, I2 = 36.9%). Incremental CDR was statistically significantly higher for European/Scandinavian studies, all using a "paired" design where women had both tests (2.4 per 1000 screens, 95% CI = 1.9 to 2.9, P < .001, I2 = 0.0%) compared with US ("unpaired") studies (1.1 per 1000 screens, 95% CI = 0.8 to 1.5, P < .001, I2 = 0.0%; P < .001 between strata). The recall rate for tomosynthesis was statistically significantly lower than for 2D mammography (pooled absolute reduction = -2.2%, 95% CI = -3.0 to -1.4, P < .001, I2 = 98.2%). Stratified analyses showed a decrease in US studies (pooled difference in recall rate = -2.9%, 95% CI = -3.5 to -2.4, P < .001, I2 = 92.9%) but not European/Scandinavian studies (0.5% increase in recall, 95% CI = -0.1 to 1.2, P = .12, I2 = 93.5%; P < .001 between strata). Results were similar in sensitivity analyses excluding studies with overlapping cohorts. Conclusions Tomosynthesis improves CDR and reduces recall; however, effects are dependent on screening setting, with greater improvement in CDR in European/Scandinavian studies (biennial screening) and reduction in recall in US studies with high baseline recall.

159 citations


Journal ArticleDOI
TL;DR: In women with mammographically dense breasts, DBT+/−DM increased CDR significantly (versus DM) in screening and diagnosis and the effect of DBT + DM on recall rate in screening dense breasts varied between studies.
Abstract: This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%–90%) versus DM alone (69%–86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02–1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20–1.47 for retrospective studies; RR: 1.52, 95% CI 1.08–2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64–0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76–1.63). In women with mammographically dense breasts, DBT+/−DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/−DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

78 citations


Journal ArticleDOI
TL;DR: Ultrasound detected more BCs but caused more false positives than tomosynthesis, underscoring trade-offs in screening outcomes when adjunct imaging is used for screening dense breasts.

73 citations


Journal ArticleDOI
TL;DR: These findings show a modest increase of radiation dose to the breast by tomosynthesis compared to FFDM, and its use in conjunction with synthetic 2D images should not be deterred by concerns regarding radiation burden, and should draw on evidence of potential clinical benefit.
Abstract: To compare radiation dose delivered by digital mammography (FFDM) and breast tomosynthesis (DBT) for a single view. 4,780 FFDM and 4,798 DBT images from 1,208 women enrolled in a screening trial were used to ground dose comparison. Raw images were processed by an automatic software to determine volumetric breast density (VBD) and were used together with exposure data to compute the mean glandular dose (MGD) according to Dance’s model. DBT and FFDM were compared in terms of operation of the automatic exposure control (AEC) and MGD level. Statistically significant differences were found between FFDM and DBT MGDs for all views (CC: MGDFFDM=1.366 mGy, MGDDBT=1.858 mGy; p<0.0001; MLO: MGDFFDM=1.374 mGy, MGDDBT=1.877 mGy; p<0.0001). Considering the 4,768 paired views, Bland-Altman analysis showed that the average increase of DBT dose compared to FFDM is 38 %, and a range between 0 % and 75 %. Our findings show a modest increase of radiation dose to the breast by tomosynthesis compared to FFDM. Given the emerging role of DBT, its use in conjunction with synthetic 2D images should not be deterred by concerns regarding radiation burden, and should draw on evidence of potential clinical benefit. • Most studies compared tomosynthesis in combination with mammography vs. mammography alone. • There is some concern about the dose increase with tomosynthesis. • Clinical data show a small increase in radiation dose with tomosynthesis. • Synthetic 2D images from tomosynthesis at zero dose reduce potential harm. • The small dose increase should not be a barrier to use of tomosynthesis.

70 citations


Journal ArticleDOI
TL;DR: Radiomics features in patients with dense breasts and negative mammography appear to differ between cancerous and normal breast tissue, with evidence of correlation with tumor size and estrogen receptors.

43 citations


Journal ArticleDOI
TL;DR: Interval breast cancer rate amongst screening participants in the STORM trial was marginally lower (and screening sensitivity higher) than estimates amongst 2D-screened women; these findings should be interpreted with caution given the small number of interval cases and the sample size of the trial.

41 citations


Journal ArticleDOI
TL;DR: A descriptive review of the evidence on the impact of BD legislation can inform research priorities where BD legislation has been introduced and can be used to guide world-wide policy or practice decisions where BD Legislation may be under debate or contemplation.

37 citations


Journal ArticleDOI
TL;DR: Although the data provide some reassurance that DBT does not increase the proportion of screen-detected DCIS, they highlight mixed findings on comparative tumour characteristics, suggesting a potential for enhancing screening benefit and possibly also over-diagnosis from DBT screening.
Abstract: The Verona population-based breast cancer (BC) screening program provides biennial mammography to women aged 50–69 years. Based on emerging evidence of enhanced detection, the program transitioned to digital breast tomosynthesis (DBT) screening. This is a prospective pilot evaluation of DBT with synthesised 2D mammography screening implemented during April 2015–March 2017; the rate and characteristics of cancers detected at DBT screening were compared with those detected at the preceding digital mammography (DM) screening round (April 2013–March 2015) in the same screening program. Distribution of imaging and tumour characteristics were compared. Amongst 34,071 women screened in the Verona DBT pilot, 315 BCs were detected; 153 BCs were detected amongst 29,360 women in the DM screening round. Estimated CDRs were 9.2/1000 (95% CI 8.3–10.3) DBT screens versus 5.2/1000 (95% CI 4.4–6.1) DM screens, P < 0.001. Statistically significant differences were found in the distribution of whether recall by one/both screen readers (more BCs recalled by both readers at DBT than DM); whether detected on one/two views (higher proportion detected on only one view at DBT than DM); type of radiological lesions; tumour stage, pT and histological categories (lower proportion of DCIS/pTis, higher proportions of pT1a and pT1b, and higher proportion of invasive cancers of special types, at DBT than DM); and tumour grade (higher proportion of grade I at DBT than DM). There were no differences in distributions of nodal and hormone receptor (ER/PR) status. Our findings provide early insights into the extent that transitioning to DBT screening may modify the characteristics of screen-detected breast cancer to inform discussion regarding pros and cons of DBT screening; although our data provide some reassurance that DBT does not increase the proportion of screen-detected DCIS, they highlight mixed findings on comparative tumour characteristics, suggesting a potential for enhancing screening benefit and possibly also over-diagnosis from DBT screening.

32 citations


Journal ArticleDOI
TL;DR: Regulated availability of patient-level data of published clinical studies ( data-sharing) is expected and expected benefits include verification/advancement of knowledge, reduced cost/time of research, clinical improvement.
Abstract: The aims of this paper are to illustrate the trend towards data sharing, i.e. the regulated availability of the original patient-level data obtained during a study, and to discuss the expected advantages (pros) and disadvantages (cons) of data sharing in radiological research. Expected pros include the potential for verification of original results with alternative or supplementary analyses (including estimation of reproducibility), advancement of knowledge by providing new results by testing new hypotheses (not explored by the original authors) on pre-existing databases, larger scale analyses based on individual-patient data, enhanced multidisciplinary cooperation, reduced publication of false studies, improved clinical practice, and reduced cost and time for clinical research. Expected cons are outlined as the risk that the original authors could not exploit the entire potential of the data they obtained, possible failures in patients’ privacy protection, technical barriers such as the lack of standard formats, and possible data misinterpretation. Finally, open issues regarding data ownership, the role of individual patients, advocacy groups and funding institutions in decision making about sharing of data and images are discussed. • Regulated availability of patient-level data of published clinical studies (data-sharing) is expected. • Expected benefits include verification/advancement of knowledge, reduced cost/time of research, clinical improvement. • Potential drawbacks include faults in patients’ identity protection and data misinterpretation.

25 citations


Journal ArticleDOI
TL;DR: Little evidence exists regarding screening efficacy of adjunct imaging as part of routine surveillance in women with a history of breast cancer, but early detection of second BCs in these women improves their prognosis.
Abstract: This work reviews the evidence on breast imaging for screening (surveillance) in women with a history of breast cancer (BC). Early detection of second BCs in these women improves their prognosis based on studies using mammography (usually with clinical examinations) for surveillance. Cohort studies have estimated that mammography surveillance has moderate sensitivity (65.4%) and good specificity (98.3%), and have shown that these women are at a higher risk of interval BC than age- and breast density-matched women without a history of BC. Studies of adjunct imaging (ultrasound, magnetic resonance imaging) for surveillance that have reported detection and accuracy measures have generally shown that adjunct imaging detected more second BCs than mammography and added substantially to the amount of false-positive results; however, little evidence exists regarding screening efficacy of adjunct imaging as part of routine surveillance.

Journal ArticleDOI
TL;DR: The evidence on DBT for BC screening reinforces that DBT integrated with DM increases cancer detection rates compared to DM alone, although the extent of improved detection varied between studies.
Abstract: Introduction: Digital breast tomosynthesis (DBT) addresses some of the limitations of digital mammography (DM) by reducing the effect of overlapping tissue. Emerging data have shown that DBT increa...

Journal ArticleDOI
TL;DR: The real-world treatment patterns and overall survival for women surviving five or more years from initiation of trastuzumab for HER2+MBC are described to identify patients who may be able to safely discontinue HER2-targeted therapy.
Abstract: Patients treated with trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) are living longer, but there is little information on their outcomes and treatment experience beyond the median survival from clinical trials and real-world observational studies. We aim to describe the real-world treatment patterns and overall survival (OS) for women surviving five or more years from initiation of trastuzumab for HER2+MBC. This is a retrospective, whole-of-population cohort study of women initiating trastuzumab for HER2+MBC between 2001 and 2011, followed to 2016. We defined long-term survivors (LTS) as those patients surviving ≥ 5 years from trastuzumab initiation. We used dispensing claims to describe timing of cancer treatments used by LTS and to estimate time on and off HER2-targeted therapies, and OS from trastuzumab initiation for HER2+MBC. Of 4177 women initiating trastuzumab for HER2+MBC, 1082 (26%) survived ≥ 5 years. Median age for LTS was 54 years (IQR 46–63). At a median follow-up of 9.4 years, 36% of LTS died; their conditional probability of surviving an additional 5 years was 55%. Median time on trastuzumab and all HER2-targeted therapy was 58.9 months (27.6–88.1) and 69.1 months (35.6–124.5), respectively. 85% of LTS had a period off HER2 therapy, lasting a median of 30.4 months (8.2–NR). LTS generally receive HER2-targeted therapies for periods of time longer than in clinical trials, but most LTS also had breaks in treatment. More research is needed to understand the effects of long-term treatment and to identify patients who may be able to safely discontinue HER2-targeted therapy.

Journal ArticleDOI
TL;DR: Outcomes for trastuzumab in this heterogeneous real world population were reassuringly comparable to those from clinical trials, with the median OS > 3 years in Group Two and 25% of patients living 7 years or longer.

Journal ArticleDOI
TL;DR: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Journal ArticleDOI
01 Jun 2018-BMJ Open
TL;DR: Pre preventive programmes such as mammography screening are likely to have significant symbolic value once they are socially embedded and in situations where there is no consensus among experts on the value of established screening programmes, people may strongly prefer receiving information about their health and having the opportunity make their own choices.
Abstract: Objective To elicit informed views from Australian women aged 70–74 regarding the acceptability of ceasing to invite women their age to participate in government-funded mammography screening (BreastScreen). Design Two community juries held in 2017. Setting Greater Sydney, a metropolis of 4.5 million people in New South Wales, Australia. Participants 34 women aged 70–74 with no personal history of breast cancer, recruited by random digit dialling and previously randomly recruited list-based samples. Main outcomes and measures Jury verdict and rationale in response to structured questions. We transcribed audio-recorded jury proceedings and identified central reasons for the jury’s decision. Results The women’s average age was 71.5 years. Participants were of diverse sociocultural backgrounds, with the sample designed to include women of lower levels of educational attainment. Both juries concluded by majority verdict (16–2 and 10–6) that BreastScreen should continue to send invitations and promote screening to their age group. Reasons given for the majority position include: (1) sending the invitations shows that society still cares about older women, empowers them to access preventive health services and recognises increasing and varied life expectancy; (2) screening provides women with information that enables choice and (3) if experts cannot agree, the conservative approach is to maintain the status quo until the evidence is clear. Reasons for the minority position were the potential for harms through overdiagnosis and misallocation of scarce health resources. Conclusions Preventive programmes such as mammography screening are likely to have significant symbolic value once they are socially embedded. Arguments for programme de-implementation emphasising declining benefit because of limited life expectancy and the risks of overdiagnosis seem unlikely to resonate with healthy older women. In situations where there is no consensus among experts on the value of established screening programmes, people may strongly prefer receiving information about their health and having the opportunity make their own choices.

Journal ArticleDOI
TL;DR: There was variability in the magnitude of effect from integrating 3D-mammography (relative to screen-reading with acquired or synthesised 2D- mammography alone) on individual radiologist's TP and FP detection, although there was an overall pattern of increasing cancer detection and also increasing FP recall for most readers.

Journal ArticleDOI
TL;DR: Risk prediction models that evaluate the risk of cancers not detected by surveillance mammography should be developed to inform discussions of tailored surveillance.
Abstract: Purpose The aim of the current study was to characterize the risk of interval invasive second breast cancers within 5 years of primary breast cancer treatment. Methods We examined 65,084 surveillance mammograms from 18,366 women with a primary breast cancer diagnosis of unilateral ductal carcinoma in situ or stage I to III invasive breast carcinoma performed from 1996 to 2012 in the Breast Cancer Surveillance Consortium. Interval invasive breast cancer was defined as ipsilateral or contralateral cancer diagnosed within 1 year after a negative surveillance mammogram. Discrete-time survival models-adjusted for all covariates-were used to estimate the probability of interval invasive cancer, given the risk factors for each surveillance round, and aggregated across rounds to estimate the 5-year cumulative probability of interval invasive cancer. Results We observed 474 surveillance-detected cancers-334 invasive and 140 ductal carcinoma in situ-and 186 interval invasive cancers which yielded a cancer detection rate of 7.3 per 1,000 examinations (95% CI, 6.6 to 8.0) and an interval invasive cancer rate of 2.9 per 1,000 examinations (95% CI, 2.5 to 3.3). Median cumulative 5-year interval cancer risk was 1.4% (interquartile range, 0.8% to 2.3%; 10th to 90th percentile range, 0.5% to 3.7%), and 15% of women had ≥ 3% 5-year interval invasive cancer risk. Cumulative 5-year interval cancer risk was highest for women with estrogen receptor- and progesterone receptor-negative primary breast cancer (2.6%; 95% CI, 1.7% to 3.5%), interval cancer presentation at primary diagnosis (2.2%; 95% CI, 1.5% to 2.9%), and breast conservation without radiation (1.8%; 95% CI, 1.1% to 2.4%). Conclusion Risk of interval invasive second breast cancer varies across women and is influenced by characteristics that can be measured at initial diagnosis, treatment, and imaging. Risk prediction models that evaluate the risk of cancers not detected by surveillance mammography should be developed to inform discussions of tailored surveillance.

Journal ArticleDOI
TL;DR: Questions are raised about the value of the increasing detection of DCIS and aggressive treatment of these lesions, especially among older women, and support trials of de-escalated treatment, despite screening being well established and participation rates in the target age range remaining stable.

Journal ArticleDOI
TL;DR: The accuracy of tomosynthesis in measuring tumor size relative to pathology and compared with other tests is examined to improve breast cancer assessment and staging as a complementary role to its detection capability.
Abstract: Introduction Tomosynthesis is proposed to improve breast cancer assessment and staging as a complementary role to its detection capability. We examine the accuracy of tomosynthesis in measuring tumor size relative to pathology and compared with other tests. Areas covered A systematic literature search identified studies of tomosynthesis in estimating the size of newly diagnosed breast cancers. Descriptive analyses were performed due to heterogeneity in patients, technology, and methods between studies. Eight studies were eligible (678 patients). Mean differences (MDs) between measurements (tomosynthesis-pathology) were generally small; overestimation (MDs of 1-3 mm) and underestimation (-1 mm) were reported. Limits of agreement (LOA) ranged between ±10 mm and ±28 mm. MDs did not differ in high and low breast densities. Large underestimation (-11 mm) and wide LOA (±41 mm) were reported for invasive lobular carcinoma. MDs and LOA were lower for tomosynthesis than mammography, but differences between tests were small. Expert commentary Although tomosynthesis is a promising technology for assessing breast cancer size, few studies in that context had limitations (small sample sizes, heterogeneous populations, and technologies). Studies using current technology and appropriate statistical methods are required to establish the magnitude of improvement in measurement accuracy, and patients for whom the test may be of most benefit.

Journal ArticleDOI
TL;DR: Patients starting trastuzumab for MBC following (neo)adjuvant trastzumab had a median treatment duration of 1 year and OS of almost 2 years, and these data help inform clinical practice and service planning for this under-researched population.
Abstract: Patients treated with (neo)adjuvant trastuzumab who relapse and receive trastuzumab for metastatic breast cancer (MBC) are a growing population with little outcome data given their exclusion from most clinical trials. We aim to estimate survival outcomes for this trastuzumab ‘pre-treated’ population. Population-based study of Australian women receiving trastuzumab for HER2-positive MBC between 2006 and 2014, who also received (neo)adjuvant trastuzumab. We used Kaplan–Meier methods to estimate the following: overall survival (OS) from initiation of trastuzumab for MBC; duration of trastuzumab for MBC; and time from last (neo)adjuvant trastuzumab to first trastuzumab for MBC. Of 3199 patients dispensed trastuzumab for MBC, 634 (20%) had received (neo)adjuvant traztuzumab. Pre-treated patients had a median (interquartile range) OS of 21.8 months (10.9–51.6), trastuzumab duration of 12.8 months (4.7–17.5), and time from last (neo)adjuvant trastuzumab to first trastuzumab for MBC of 15.6 months (6.5–28.6). Median OS for patients initiating trastuzumab <12 months and ⩾12 months from their last (neo)adjuvant trastuzumab were 17.1 months and 24.8 months, respectively. Patients starting trastuzumab for MBC following (neo)adjuvant trastuzumab had a median treatment duration of 1 year and OS of almost 2 years. These data help inform clinical practice and service planning for this under-researched population.

Journal ArticleDOI
TL;DR: This is a protocol for a Cochrane Review (Intervention) to assess the effect of screening mammography for breast cancer on overdiagnosis in women aged 40 years and older at average risk of breast cancer.
Abstract: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effect of screening mammography for breast cancer on overdiagnosis in women aged 40 years and older at average risk of breast cancer.

Journal ArticleDOI
26 Jul 2018-PLOS ONE
TL;DR: A substantial amount of treatment did not adhere to prescribing restrictions during the relatively simpler treatment era of the study period, highlighting that the regulation and funding of HER2-targeted treatment will become more challenging.
Abstract: Background Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001-2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further sub-clusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging.

Posted ContentDOI
16 May 2018-bioRxiv
TL;DR: A substantial amount of treatment did not adhere to prescribing restrictions during the relatively simpler treatment era of this study period, highlighting that the regulation and funding of HER2-targeted treatment will become more challenging.
Abstract: Background Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Methods and findings Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating trastuzumab for HER2+MBC between 2001-2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further sub-clusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging.

Proceedings ArticleDOI
01 Aug 2018
TL;DR: The incidence of all stages of BC has increased over the past forty years, with the greatest rise seen during the established screening period for women aged 50–69 years.
Abstract: Objectives Screening mammography aims to improve breast cancer (BC) prognosis by increasing the incidence of early-stage tumours in order to decrease the incidence of late-stage cancer, but no reports have investigated these potential effects in an Australian population. Therefore, we aim to describe temporal trends in the incidence of stage-specific breast cancer in New South Wales, Australia, between 1972 and 2012. Method An observational study of all women who received a diagnosis of BC from 1972–2012 as recorded in the NSW Cancer Registry, a population-based registry with almost complete coverage and high rates of histological verification. We analysed trends in stage-specific incidence before screening and compared them to periods after screening began. Our primary group of interest was women in the target age range of 50–69 years, though trends in women outside the target age were also assessed. Results Screening was not associated with lower incidence of late-stage BC at diagnosis. Incidence for all stages remained higher than prescreening levels. In women aged 50–69 years, the incidence of carcinoma in situ (CIS), localised and regional BC has more than doubled compared to the prescreening era, with incidence rate ratios ranging from 2.0 for regional (95% CI 1.95 to 2.13) to 121.8 for CIS (95% CI 82.58 to 179.72). Before the introduction of screening there was a downward trend in distant metastatic BC incidence, and after the introduction of screening there was an increase (IRR 1.8; 95% CI 1.62 to 2.00). In women too young to screen the incidence of late-stage BC at diagnosis also increased, whereas localised disease was stable. Conclusions The incidence of all stages of BC has increased over the past forty years, with the greatest rise seen during the established screening period for women aged 50–69 years. Our findings suggest that some of the expected benefits of screening may not have been realised and are consistent with overdiagnosis.

05 Jan 2018
TL;DR: Poster: "ECR 2018 / C-0514 / Patient dose reduction combining tomosynthesis with synthetic instead of standard mammography" by G. Gennaro and N. Houssami.
Abstract: Poster: "ECR 2018 / C-0514 / Patient dose reduction combining tomosynthesis with synthetic instead of standard mammography " by: " G. Gennaro 1, D. Bernardi2, N. Houssami3; 1Padua/IT, 2Trento, TN/IT, 3Sydney/AU"


Journal ArticleDOI
TL;DR: In the rapidly progressive world of cancer research and discovery, concerns about overdetection, or overdiagnosis, whether relating to breast cancer or other types of cancer, seem remote and counterintuitive.
Abstract: In the rapidly progressive world of cancer research and discovery, concerns about overdetection, or overdiagnosis, whether relating to breast cancer or other types of cancer, seem remote and counterintuitive.