| 1. |
- Jurrius, Patriek, et al.
(författare)
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Invasive breast cancer over four decades reveals persisting poor metastatic outcomes in treatment resistant subgroup - the "ATRESS" phenomenon
- 2020
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Ingår i: Breast. - : CHURCHILL LIVINGSTONE. - 0960-9776 .- 1532-3080. ; 50, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Background: Major advances in breast cancer treatment have led to a reducuction in mortality. However, there are still women who are not cured. We hypothesize there is a sub-group of women with treatment-resistant cancers causing early death.Methods: Between 1975 and 2006, 5392 women with invasive breast cancer underwent surgery at Guy's Hospital, London. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, secondary metastasis, and death were prospectively recorded. We considered four time periods (1975-1982, 1983-1990, 1991-1998, 1999-2006). Risks and time to event analysis were performed with Cox proportional hazards model and Kaplan-Meier estimation.Results: Unadjusted hazard ratios for developing metastasis and overall mortality relative to the 1975-1982 cohort decreased steadily to 0.23 and 0.63, respectively in 1999-2006. However, metastasis-free interval shortened, with the proportion of women developing metastasis <= 5 years increasing from 73.9% to 83.0%. Furthermore, median post-metastatic survival decreased from 1.49 years to 0.94 years. Applying our risk criteria identified the presence of +/- 200 patients in each cohort who developed metastasis early and died within a much shorter time frame.Conclusions: Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter metastasis-free and post-metastatic survival who are unresponsive to available treatment remains. This may be due to the ATRESS phenomenon (adjuvant therapy-related shortening of survival) secondary to preselection inherent in adjuvant therapy, successful treatment of less malignant tumour cells and treatment-induced resistance in the remaining tumour clones.
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| 2. |
- Lambert, Paul C, et al.
(författare)
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Quantifying differences in breast cancer survival between England and Norway
- 2011
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 35:6, s. 526-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Survival from breast cancer is lower in the UK than in some other European countries. We compared survival in England and Norway by age and time from diagnosis. METHODS: We included 303,648 English and 24,919 Norwegian cases of breast cancer diagnosed 1996-2004 using flexible parametric relative survival models, enabling improved quantification of differences in survival. Crude probabilities were estimated to partition the probability of death due to all causes into that due to cancer and other causes and to estimate the number of "avoidable" deaths. RESULTS: England had lower relative survival for all ages with the difference increasing with age. Much of the difference was due to higher excess mortality in England in the first few months after diagnosis. Older patients had a higher proportion of deaths due to other causes. At 5 years post diagnosis, a woman aged 85 in England had probabilities of 0.35 of dying of cancer and 0.32 of dying of other causes, whilst in Norway they were 0.26 and 0.35. By eight years the number of "avoidable" all-cause deaths in England was 1020 with the number of "avoidable" breast cancer related deaths 1488. CONCLUSION: Lower breast cancer survival in England is mainly due to higher mortality in the first year after diagnosis. Crude probabilities aid our understanding of the impact of disease on individual patients and help assess different treatment options.
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| 3. |
- Lawler, Katherine, et al.
(författare)
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Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread : a case control study
- 2017
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Ingår i: Breast Cancer Research. - : BIOMED CENTRAL LTD. - 1465-5411 .- 1465-542X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated.Results: Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort.Conclusion: This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.
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| 4. |
- Melvin, Jennifer C., et al.
(författare)
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Family history of breast cancer and its association with disease severity and mortality
- 2016
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 5:5, s. 942-949
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Tidskriftsartikel (refereegranskat)abstract
- A family history (FH) of breast cancer (BC) is known to increase an individual's risk of disease onset. However, its role in disease severity and mortality is less clear. We aimed to ascertain associations between FH of BC, severity and BC-specific mortality in a hospital-based cohort of 5354 women with prospective information on FH. We included women diagnosed at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2012 (n = 5354). BC severity was defined and categorized as good, moderate, and poor prognosis. Data on BC-specific mortality was obtained from the National Cancer Registry and medical records. Associations between FH and disease severity or BC-specific mortality were evaluated using proportional odds models and Cox proportional hazard regression models, respectively. Available data allowed adjustment for potential confounders (e.g., treatment, socioeconomic status, and ethnicity). FH of any degree was not associated with disease severity at time of diagnosis (adjusted proportional OR: 1.00 [95% CI: 0.85 to 1.17]), which remained true also after stratification by period of diagnosis. FH of BC was not associated with BC-mortality HR: 0.99 (95% CI: 0.93 to 1.05). We did not find evidence to support an association between FH of BC and severity and BC-specific mortality. Our results indicate that clinical management should not differ between women with and without FH, when the underlying mutation is unknown.
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| 5. |
- Melvin, Jennifer C., et al.
(författare)
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Progression of breast cancer following locoregional ipsilateral recurrence : importance of interval time
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 114:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy's and St Thomas' NHS Foundation Trust. Methods: Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression. Results: Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5-1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71-11.99), when compared with women who did not experience LR. Conclusions: It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.
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| 6. |
- Moller, Henrik, et al.
(författare)
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Recent childbirth is an adverse prognostic factor in breast cancer and melanoma, but not in Hodgkin lymphoma
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:17, s. 3686-3693
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between gestation, childbirth and cancer prognosis is unknown for most cancers (e. g. Hodgkin lymphoma), whereas a body of evidence exists for melanoma and breast cancer. Methods: The national cancer registration and hospital discharge data for women in England (1998-2007) were linked, and the records for Hodgkin lymphoma, melanoma and breast cancer were indexed as to whether women had delivered a child in separate time periods prior to their cancer diagnosis. Survival analyses were conducted in order to characterise prognosis in relation to childbirth, with statistical adjustment for age and (where possible) stage. Findings: For melanoma and breast cancer, survival was strongly reduced in women who gave birth in the year prior to cancer diagnosis. The age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were 2.06 (1.42-3.01) for melanoma and 1.84 (1.64-2.06) for breast cancer. The associations were only slightly attenuated by further adjustment for tumour stage. For breast cancer, the excess death rate in women with a recent childbirth peaked at 2 years and remained elevated for 6 to 8 years. Previous childbirth had no overall effect on the outcome of Hodgkin lymphoma. Interpretation: Melanoma and breast cancer prognosis are adversely affected by recent gestation and childbirth in a way that is not due to stage of the cancer, but rather to inherent biological properties of the tumours. Possible biological mechanisms include immunosuppression (melanoma), the hormonal milieu in gestation and a tumour promoting microenvironment post-partum (breast cancer).
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| 7. |
- Möller, Henrik, et al.
(författare)
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Breast cancer survival in England, Norway and Sweden : a population-based comparison
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:11, s. 2630-2638
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Tidskriftsartikel (refereegranskat)abstract
- Several international studies have found that survival from breast cancer is lower in the United Kingdom than in some other European countries. We have compared breast cancer survival between the national populations of England, Norway and Sweden, with a view to identifying subsets of patients with particularly good or adverse survival outcomes. We extracted cases of breast cancer in women diagnosed 1996-2004 from the national cancer registries of the 3 countries. The study comprised 303,657 English cases, 24,919 Norwegian cases and 57,512 cases from Sweden. Follow-up was in 2001-2004. The main outcome measures were 5-year cumulative relative survival and excess death rates, stratified by age and period of follow-up. In comparison with Norway and Sweden, the excess mortality in England was particularly pronounced in the first month and in the first year after diagnosis, and generally more marked in the oldest age groups. Compared with Norwegian patients, 81% of the excess deaths in the English patients occurred in the first 2 years after diagnosis. Our findings emphasise the importance of awareness of symptoms and early detection as the main strategy to improve breast cancer survival in the United Kingdom.
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| 8. |
- Møller, Henrik, et al.
(författare)
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High lung cancer surgical procedure volume is associated with shorter length of stay and lower risks of re-admission and death : National cohort analysis in England.
- 2016
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 64, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- It is debated whether treating cancer patients in high-volume surgical centres can lead to improvement in outcomes, such as shorter length of hospital stay, decreased frequency and severity of post-operative complications, decreased re-admission, and decreased mortality. The dataset for this analysis was based on cancer registration and hospital discharge data and comprised information on 15,738 non-small-cell lung cancer patients resident and diagnosed in England in 2006-2010 and treated by surgical resection. The number of lung cancer resections was computed for each hospital in each calendar year, and patients were assigned to a hospital volume quintile on the basis of the volume of their hospital. Hospitals with large lung cancer surgical resection volumes were less restrictive in their selection of patients for surgical management and provided a higher resection rate to their geographical population. Higher volume hospitals had shorter length of stay and the odds of re-admission were 15% lower in the highest hospital volume quintile compared with the lowest quintile. Mortality risks were 1% after 30 d and 3% after 90 d. Patients from hospitals in the highest volume quintile had about half the odds of death within 30 d than patients from the lowest quintile. Variations in outcomes were generally small, but in the same direction, with consistently better outcomes in the larger hospitals. This gives support to the ongoing trend towards centralisation of clinical services, but service re-organisation needs to take account of not only the size of hospitals but also referral routes and patient access.
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| 9. |
- Sullivan, Richard, et al.
(författare)
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Delivering affordable cancer care in high-income countries
- 2011
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Ingår i: The Lancet Oncology. - London : Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:10, s. 933-980
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Tidskriftsartikel (refereegranskat)abstract
- The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
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| 10. |
- Sullivan, Richard, et al.
(författare)
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Global cancer surgery: delivering safe, affordable, and timely cancer surgery
- 2015
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Ingår i: The Lancet Oncology. - 1474-5488. ; 16:11, s. 1193-1224
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Tidskriftsartikel (refereegranskat)abstract
- Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, aff ordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and fi nancing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US$ 6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery-eg, pathology and imaging-are also inadequate. Our analysis identifi ed substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, aff ordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.
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