Despite decades of laboratory, epidemiological and clinical research, breast cancer incidence continues to rise. Breast cancer remains the leading cancer-related cause of disease burden for women, ...affecting one in 20 globally and as many as one in eight in high-income countries. Reducing breast cancer incidence will likely require both a population-based approach of reducing exposure to modifiable risk factors and a precision-prevention approach of identifying women at increased risk and targeting them for specific interventions, such as risk-reducing medication. We already have the capacity to estimate an individual woman's breast cancer risk using validated risk assessment models, and the accuracy of these models is likely to continue to improve over time, particularly with inclusion of newer risk factors, such as polygenic risk and mammographic density. Evidence-based risk-reducing medications are cheap, widely available and recommended by professional health bodies; however, widespread implementation of these has proven challenging. The barriers to uptake of, and adherence to, current medications will need to be considered as we deepen our understanding of breast cancer initiation and begin developing and testing novel preventives.
Public opinion in recent years has soured on multiculturalism, due in large part to fears of radical Islam. In Multiculturalism without Culture, Anne Phillips contends that critics misrepresent ...culture as the explanation of everything individuals from minority and non-Western groups do. She puts forward a defense of multiculturalism that dispenses with notions of culture, instead placing individuals themselves at its core. Multiculturalism has been blamed for encouraging the oppression of women--forced marriages, female genital cutting, school girls wearing the hijab. Many critics opportunistically deploy gender equality to justify the retreat from multiculturalism, hijacking the equality agenda to perpetuate cultural stereotypes. Phillips informs her argument with the feminist insistence on recognizing women as agents, and defends her position using an unusually broad range of literature, including political theory, philosophy, feminist theory, law, and anthropology. She argues that critics and proponents alike exaggerate the unity, distinctness, and intractability of cultures, thereby encouraging a perception of men and women as dupes constrained by cultural dictates.
No one wants to be treated like an object, regarded as an item of property, or put up for sale. Yet many people frame personal autonomy in terms of self-ownership, representing themselves as property ...owners with the right to do as they wish with their bodies. Others do not use the language of property, but are similarly insistent on the rights of free individuals to decide for themselves whether to engage in commercial transactions for sex, reproduction, or organ sales. Drawing on analyses of rape, surrogacy, and markets in human organs,Our Bodies, Whose Property?challenges notions of freedom based on ownership of our bodies and argues against the normalization of markets in bodily services and parts. Anne Phillips explores the risks associated with metaphors of property and the reasons why the commodification of the body remains problematic.
What, she asks, is wrong with thinking of oneself as the owner of one's body? What is wrong with making our bodies available for rent or sale? What, if anything, is the difference between markets in sex, reproduction, or human body parts, and the other markets we commonly applaud? Phillips contends that body markets occupy the outer edges of a continuum that is, in some way, a feature of all labor markets. But she also emphasizes that we all have bodies, and considers the implications of this otherwise banal fact for equality. Bodies remind us of shared vulnerability, alerting us to the common experience of living as embodied beings in the same world.
Examining the complex issue of body exceptionalism,Our Bodies, Whose Property?demonstrates that treating the body as property makes human equality harder to comprehend.
IMPORTANCE: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. OBJECTIVES: To estimate age-specific risks of breast, ovarian, and ...contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. EXPOSURES: BRCA1/2 mutations, family cancer history, and mutation location. MAIN OUTCOMES AND MEASURES: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. RESULTS: Among 3886 women (median age, 38 years; interquartile range IQR, 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio HR for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). CONCLUSIONS AND RELEVANCE: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
The Oxford Handbook of Political Theory provides comprehensive and critical coverage of the lively and contested field of political theory. Long recognized as one of the main branches of political ...science, political theory has in recent years burgeoned in many different directions. In this book forty-five articles by distinguished political theorists look at the state of the field, where it has been in the recent past, and where it is likely to go in future. They examine political theory's edges as well as its core, the globalizing context of the field, and the challenges presented by social, economic, and technological changes. The Handbook is one of The Oxford Handbooks of Political Science — a ten-volume set of reference books offering authoritative and engaging critical overviews of the state of political science.
Independent validation is essential to justify use of models of breast cancer risk prediction and inform decisions about prevention options and screening. Few independent validations had been done ...using cohorts for common breast cancer risk prediction models, and those that have been done had small sample sizes and short follow-up periods, and used earlier versions of the prediction tools. We aimed to validate the relative performance of four commonly used models of breast cancer risk and assess the effect of limited data input on each one's performance.
In this validation study, we used the Breast Cancer Prospective Family Study Cohort (ProF-SC), which includes 18 856 women from Australia, Canada, and the USA who did not have breast cancer at recruitment, between March 17, 1992, and June 29, 2011. We selected women from the cohort who were 20–70 years old and had no previous history of bilateral prophylactic mastectomy or ovarian cancer, at least 2 months of follow-up data, and information available about family history of breast cancer. We used this selected cohort to calculate 10-year risk scores and compare four models of breast cancer risk prediction: the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm model (BOADICEA), BRCAPRO, the Breast Cancer Risk Assessment Tool (BCRAT), and the International Breast Cancer Intervention Study model (IBIS). We compared model calibration based on the ratio of the expected number of breast cancer cases to the observed number of breast cancer cases in the cohort, and on the basis of their discriminatory ability to separate those who will and will not have breast cancer diagnosed within 10 years as measured with the concordance statistic (C-statistic). We did subgroup analyses to compare the performance of the models at 10 years in BRCA1 or BRCA2 mutation carriers (ie, BRCA-positive women), tested non-carriers and untested participants (ie, BRCA-negative women), and participants younger than 50 years at recruitment. We also assessed the effect that limited data input (eg, restriction of the amount of family history and non-genetic information included) had on the models' performance.
After median follow-up of 11·1 years (IQR 6·0–14·4), 619 (4%) of 15 732 women selected from the ProF-SC cohort study were prospectively diagnosed with breast cancer after recruitment, of whom 519 (84%) had histologically confirmed disease. BOADICEA and IBIS were well calibrated in the overall validation cohort, whereas BRCAPRO and BCRAT underpredicted risk (ratio of expected cases to observed cases 1·05 95% CI 0·97–1·14 for BOADICEA, 1·03 0·96–1·12 for IBIS, 0·59 0·55–0·64 for BRCAPRO, and 0·79 0·73–0·85 for BRCAT). The estimated C-statistics for the complete validation cohort were 0·70 (95% CI 0·68–0·72) for BOADICEA, 0·71 (0·69–0·73) for IBIS, 0·68 (0·65–0·70) for BRCAPRO, and 0·60 (0·58–0·62) for BCRAT. In subgroup analyses by BRCA mutation status, the ratio of expected to observed cases for BRCA-negative women was 1·02 (95% CI 0·93–1·12) for BOADICEA, 1·00 (0·92–1·10) for IBIS, 0·53 (0·49–0·58) for BRCAPRO, and 0·97 (0·89–1·06) for BCRAT. For BRCA-positive participants, BOADICEA and IBIS were well calibrated, but BRCAPRO underpredicted risk (ratio of expected to observed cases 1·17 95% CI 0·99–1·38 for BOADICEA, 1·14 0·96–1·35 for IBIS, and 0·80 0·68–0·95 for BRCAPRO). We noted similar patterns of calibration for women younger than 50 years at recruitment. Finally, BOADICEA and IBIS predictive scores were not appreciably affected by limiting input data to family history for first-degree and second-degree relatives.
Our results suggest that models that include multigenerational family history, such as BOADICEA and IBIS, have better ability to predict breast cancer risk, even for women at average or below-average risk of breast cancer. Although BOADICEA and IBIS performed similarly, further improvements in the accuracy of predictions could be possible with hybrid models that incorporate the polygenic risk component of BOADICEA and the non-family-history risk factors included in IBIS.
US National Institutes of Health, National Cancer Institute, Breast Cancer Research Foundation, Australian National Health and Medical Research Council, Victorian Health Promotion Foundation, Victorian Breast Cancer Research Consortium, Cancer Australia, National Breast Cancer Foundation, Queensland Cancer Fund, Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and Cancer Foundation of Western Australia.
The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial ...or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers.
We analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history. The prospective cohort was further restricted to women without breast cancer when medication history was asked by questionnaire. Women were recruited from seven study centers in the United States, Canada, and Australia. Associations were estimated using multivariable Cox proportional hazards regression models adjusted for demographics, lifestyle factors, family history, and other medication use. Women were classified as regular or non-regular users of aspirin, COX-2 inhibitors, ibuprofen and other NSAIDs, and acetaminophen (control) based on self-report at follow-up of ever using the medication for at least twice a week for ≥1 month prior to breast cancer diagnosis. The main outcome was incident invasive breast cancer, based on self- or relative-report (81% confirmed pathologically).
From fully adjusted analyses, regular aspirin use was associated with a 39% and 37% reduced risk of breast cancer in the prospective (HR = 0.61; 95% CI = 0.33-1.14) and combined cohorts (HR = 0.63; 95% CI = 0.57-0.71), respectively. Regular use of COX-2 inhibitors was associated with a 61% and 71% reduced risk of breast cancer (prospective HR = 0.39; 95% CI = 0.15-0.97; combined HR = 0.29; 95% CI = 0.23-0.38). Other NSAIDs and acetaminophen were not associated with breast cancer risk in either cohort. Associations were not modified by familial risk, and consistent patterns were found by BRCA1 and BRCA2 carrier status, estrogen receptor status, and attained age.
Regular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk.
Women with hormone-receptor–negative breast cancer who received goserelin with adjuvant chemotherapy had less amenorrhea and better fertility at 2 years after treatment, and better rates of ...disease-free and overall survival, than did those who received chemotherapy alone.
Early ovarian failure is an important and potentially devastating long-term toxic effect of chemotherapy. Manifestations include menopausal symptoms, osteoporosis, and infertility. Concerns about fertility may influence treatment choices for young women with breast cancer
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despite the known survival benefit of adjuvant chemotherapy.
Trials of the coadministration of a gonadotropin-releasing hormone (GnRH) agonist with adjuvant chemotherapy for the purpose of protecting ovarian function have shown mixed results.
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A large randomized trial addressing this issue suggested that coadministration of a GnRH agonist with chemotherapy had an ovarian protective effect in a cohort of patients in which 86% had estrogen-receptor–positive breast cancer, . . .
People in the UK are living longer and with multi-morbidities, increasing the size, complexity and acuity of Community Nursing caseloads. Nurses visiting infrequently and inconsistently on a ...task-focused basis need an objective method by which to identify / quantify physical deterioration for early treatment avoiding crisis and hospital admission. The National Early Warning Score (NEWS), is the most recognised tool for identification of deterioration in acute settings but is not validated for community use. Using published frameworks for scoping review and evaluation, this study aims to explore the current evidence for use of NEWS in community settings. Although there is work to be done, particularly in terms of frequency of scoring and response, this study identifies benefits in communication and prioritisation of care as well as sensitivity, particularly in predicting poor outcomes. The identified barriers to use include integration into practice and perceived dissonance with clinical judgement.
Drawing on her own reading history, her devotion to nineteenth-century girls' books, overseas research opportunities, and her affinity for German texts and German culture, Julie Pfeiffer offers an ...analysis of the "Backfisch" tradition of girls' books that will have broad appeal. While Backfisch books offer conventional endings and patriarchal, heterosexual constraints, they nonetheless delineate space within female adolescence where heroines may explore beyond their familial boundaries, benefit from the protection and wisdom of female mentors, and learn habits, skills, and conventions that will enable them to succeed in their adult lives. Neither family stories nor orphan stories nor bildungsromane, Backfisch books "reveal another strand in the development of the girls' book, one in which girls are loved, protected, and expected to function independently of parents and siblings" (12). German texts name both the adolescent girl the Backfisch… and her short but crucial period of development the Backfischzeit, … calling our attention to a shared German-American generic structure in girls' fiction of the 1850s, '60s, '70s, and '80s" (43).
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