72 research outputs found

    Tobacco and the Escalating Global Cancer Burden

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    The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world

    Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality?

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    Radiotherapy is an integral component of loco-regional therapy for breast cancer. Randomized controlled trials indicate that increasing the extent of extirpative surgery primarily reduces the risk of local recurrences, while the addition of radiotherapy to surgery can also reduce the risk of distant recurrences, thereby lowering breast cancer-specific mortality. This may suggest an “abscopal” effect beyond the immediate zone of loco-regional irradiation that favorably perturbs the natural history of distant micrometastases. Immunological phenomena such as “immunogenic cell death” provide a plausible mechanistic link between the local and systemic effects of radiation. Radiotherapy treatment can stimulate both pro-immunogenic and immunosuppressive pathways with a potential net beneficial effect on anti-tumor immune activity. Upregulation of programmed cell death ligand (PD-L1) by radiotherapy is an immunosuppressive pathway that could be approached with anti-PD-L1 therapy with potential further improvement in survival. The world overview of randomized trials indicates that the breast cancer mortality reduction from adjuvant radiotherapy is delayed relative to that of adjuvant systemic treatments, and similar delays in the separation of survival curves are evident in the majority of randomized immunotherapy trials demonstrating treatment efficacy. In this article, we hypothesize that an abscopal effect may explain the benefit of radiotherapy in reducing breast cancer mortality, and that It might be possible to harness and augment this effect with systemic agents to reduce the risk of late recurrences

    Highlights of the San Antonio Breast Cancer Symposium 2019 Part 2: the challenges of tumor heterogeneity

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    The 42nd annual San Antonio Breast Cancer Symposium (SABCS) was convened in San Antonio Texas on December 10 – 14, 2019. More than 7000 clinicians and scientists from around the world participated in the symposium that featured presentations and keynote talks pertaining to epidemiology and biology, screening/prevention, loco-regional treatment together with systemic therapies for early and late stage disease. This two-part report highlights a selection of important studies presented at this premier breast cancer event with the first part focusing on stromal-epithelial interactions, long term outcomes of hormone replacement therapy, androgen receptor targeting, high risk MRI screening and whether breast surgery can be safely omitted in exceptional responders after neoadjuvant chemotherapy

    Breast cancer trends among black and white women in the United States

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    A B S T R A C T Purpose Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors. Patients and Methods Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression. Results For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks. Conclusion The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends

    Extended endocrine therapy in early breast cancer: how long and who for?

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    Endocrine therapy for early stage breast cancer is currently in a state of flux with much uncertainty about choice of agents and duration of therapy. The standard treatment span of 5 years usually incorporates an aromatase inhibitor in the majority of postmenopausal patients. Hormonal therapy has a cytostatic action that provides a biological rationale for continuing treatment for more prolonged periods to reduce risk of late recurrence in estrogen receptor-positive disease. Several trials of extended endocrine therapy for periods varying from 7.5 to 10 years have shown mixed results for gains in disease-free survival. The challenge is to assimilate available data and apply clinical judgment to tailor therapies taking account of intrinsic risk of disease recurrence, patient preference, tolerability to date, and co-morbidities

    Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis

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    Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 50 end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development
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