Breast cancer-The catalyst of contemporary trials design.

Surgical trials in breast cancer have catalyzed contemporary trial design for solid organ cancers and are a prime example of surgeons taking the lead in clinical trial design. Surgeons have lead trials that have improved patient outcomes and quality of life without sacrificing oncologic safety. We have evolved from radical mastectomy to breast conservation and sentinel node biopsy. Contemporary trial design in breast cancer now focus on personalizing care based on tumor genomics.

Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992-2016.

BACKGROUND: Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making. METHODS: We examined CBC risk among 419,818 women (age 30-84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004-2015, follow-up through 2016). RESULTS: Over a median follow-up of 8 years (range 1-25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17-2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90-1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61-2.21%) in younger women with a first ER-negative tumor. CONCLUSION: Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

The development of breast radiology: the Acta Radiologica perspective.

The encouraging results of modern breast cancer care builds on tremendous improvements in diagnostics and therapy during the 20th century. Scandinavian countries have made important footprints in the development of breast diagnostics regarding technical development of imaging, cell and tissue sampling methods and, not least, population screening with mammography. The multimodality approach in combination with multidisciplinary clinical work in breast cancer serve as a role model for the management of many cancer types worldwide. The development of breast radiology is well represented in the research published in this journal and this historical review will describe the most important steps.

Historical trends in breast Cancer among women in China from age-period-cohort modeling of the 1990-2015 breast Cancer mortality data.

BACKGROUND: Evidence on historical trends extracted embedded in recent data can advance our understanding of the epidemiology of breast cancer for Chinese women. China is a country with significant political, socioeconomic, and cultural events since the 1900s; however, no such studies are reported in the literature. METHODS: Age-specific mortality rates of breast cancer during 1990-2015 in China were analyzed using APC modeling (age-period-cohort modeling) method. Net effect from birth cohort was derived to measure cancer mortality risk during 1906-1990 when no mortality data were collected, and net effect from time period was derived to measure cancer mortality risk during 1990-2015 when data were collected. Model parameters were estimated using intrinsic estimator, a novel method to handle collinearity. The estimated effects were numerical differentiated to enhance presentations of time/age trend. RESULTS: Breast cancer mortality rate per 100,000 women increased from 6.83 in 1990 to 12.07 in 2015. After controlling for age and period, the risk of breast cancer mortality declined from 0.626 in 1906-10 to - 1.752 in 1991-95 (RR = 0.09). The decline consisted of 3 phases, a gradual phase during 1906-1940, a moderate phase with some fluctuations during 1941-1970, and a rapid phase with large fluctuations during 1971-1995. After controlling for age and cohort, the risk of breast cancer mortality increased from - 0.141 in 1990 to 0.258 in 2015 (RR = 1.49) with an acceleration after 2005. The time trends revealed by both the cohort effect and the period effect were in consistency with the significant political and socioeconomic events in China since the 1900s. CONCLUSIONS: With recent mortality data in 1990-2015, we detected the risk of breast cancer mortality for Chinese women over a long period from 1906 to 2015. The risk declined more than 90% from the highest level in 1906-10 to the lowest in 1990-95, followed by an increase of 49% from 1990 to 2015. Findings of this study connected historical evidence with recent data, supporting further research to exam the relationship between development and risk of breast cancer for medical and health decision-making at the population level and prevention and treatment at the individual level.

Cancer and the emotions in 18th-century literature.

This essay argues that the emotional rhetoric of today's breast cancer discourse-with its emphasis on stoicism and 'positive thinking' in the cancer patient, and its use of sympathetic feeling to encourage charitable giving-has its roots in the long 18th century. While cancer had long been connected with the emotions, 18th-century literature saw it associated with both 'positive' and 'negative' feelings, and metaphors describing jealousy, love and other sentiments as 'like a cancer' were used to highlight the danger of allowing feelings-even benevolent or pleasurable feelings-to flourish unchecked. As the century wore on, breast cancer in particular became an important literary device for exploring the dangers of feeling in women, with writers of both moralising treatises and sentimental novels connecting the growth or development of cancer with the indulgence of feeling, and portraying emotional self-control as the only possible form of resistance against the disease. If, as Barbara Ehrenreich suggests, today's discourse of 'positive thinking' has been mobilised to make patients with breast cancer more accepting of their diagnosis and more cooperative with punitive treatment regimens, then 18th-century fictional exhortations to stay cheerful served similarly conservative political and economic purposes, encouraging continued female submission to male prerogatives inside and outside the household.

[A historical view of breast implants: Controversy on silicones and breast implant associated -anaplastic large cell lymphoma]. / Seins à dessein. Une histoire d' implants mammaires : controverses autour de la silicone et du lymphome anaplasique a grandes cellules-associe implants mammaires.

Since the dawn of breast implantation back in the sixties, five generations of breast implants have tried to provide the most natural-looking results while striving to eliminate the risk of unpleasant ruptures or capsular contractures. National Health regulators (i.e. the FDA in USA and ANSM in France) have had an "after the facts" reaction, which led to a so-called "dirty war" among producers in the form of a 1992 Silicone's Moratorium (after suspicions of associated cancer or immune-related disorders) all this under the rigid oversight of a FDA director, who seemed more sensible to media scandal than scientific data. After more than a decade of consistent scientific evidence, the interdiction was finally ended in France in 2001 and in the USA in 2006, however the scandals resurfaced again in 2011 after a proven fraud on the "PIP - affair" and most recently with "breast implant associated - anaplastic large cell lymphoma", an extremely serious and rare pathology, treated only by surgical means, until further research. We describe also a chronology on the way the FDA finally recognized this dramatic complication.

Chemotherapy Costs and 21-Gene Recurrence Score Genomic Testing Among Medicare Beneficiaries With Early-Stage Breast Cancer, 2005 to 2011.

BACKGROUND: This study examined whether associations between 21-gene recurrence score (RS) genomic testing and lower costs among patients with early-stage, estrogen receptor-positive breast cancer are observable in real-world data from the Medicare population. METHODS: A retrospective cohort study was conducted using SEER-Medicare data for a nationally representative sample of Medicare beneficiaries diagnosed from 2005 through 2011. The main outcomes were associations between RS testing and overall and chemotherapy-specific costs. The primary analysis was restricted to patients aged 66 to 75 years. RESULTS: The primary analysis comprised 30,058 patients. Mean costs 1 year after diagnosis were $35,940 [SD, $28,894] overall, $51,127 [33,386] for clinically high-risk disease, $33,225 [$27,711] for intermediate-risk disease, and $26,695 [$19,532] for low-risk disease. Chemotherapy-specific costs followed similar trends. In multivariable analyses, RS testing was associated with significantly lower costs among high-risk patients in terms of both relative costs (cost ratio, 0.88; 99% CI, 0.82-0.94) and absolute costs ($6,606; 99% CI, $39,223-$9,290). Higher costs among low-risk and intermediate-risk patients were mainly caused by higher noncancer costs. In sensitivity analyses that included all patients aged ≥66 years (N=64,996), associations between RS testing and costs among high-risk patients were similar but less pronounced because of lower overall use of chemotherapy. CONCLUSIONS: RS testing was associated with lower overall and chemotherapy-related costs in patients with high-risk disease, consistent with lower chemotherapy use among these patients. Higher overall costs for patients with intermediate-risk and low-risk disease were driven largely by non-treatment-related costs.

Differences in breast cancer incidence among young women aged 20-49 years by stage and tumor characteristics, age, race, and ethnicity, 2004-2013.

PURPOSE: Younger women diagnosed with breast cancer have poorer prognoses and higher mortality compared to older women. Young black women have higher incidence rates of breast cancer and more aggressive subtypes than women of other races/ethnicities. In this study, we examined recent trends and variations in breast cancer incidence among young women in the United States. METHODS: Using 2004-2013 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program data, we calculated breast cancer incidence rates and trends and examined variations in stage, grade, and tumor subtype by age and race/ethnicity among young women aged 20-49 years. RESULTS: The majority of breast cancer cases occurred in women aged 40-44 and 45-49 years (77.3%). Among women aged < 45 years, breast cancer incidence was highest among black women. Incidence trends increased from 2004 to 2013 for Asian or Pacific Islander (API) women and white women aged 20-34 years. Black, American Indian or Alaska Native, and Hispanic women had higher proportions of cases diagnosed at later stages than white and API women. Black women had a higher proportion of grade III-IV tumors than other racial/ethnic groups. Across all age groups, incidence rates for triple-negative breast cancer were significantly higher in black women than women of other races/ethnicities, and this disparity increased with age. CONCLUSIONS: Breast cancer among young women is a highly heterogeneous disease. Differences in tumor characteristics by age and race/ethnicity suggest opportunities for further research into personal and cultural factors that may influence breast cancer risk among younger women.

Association between physician characteristics and the use of 21-gene recurrence score genomic testing among Medicare beneficiaries with early-stage breast cancer, 2008-2011.

PURPOSE: We sought to determine whether physician-level characteristics were associated with 21-gene recurrence score (RS) genomic testing to evaluate recurrence risk and benefit of adjuvant chemotherapy in patients with estrogen receptor-positive, node-negative breast cancer. METHODS: Retrospective cohort study of a nationally representative sample of Medicare beneficiaries using Surveillance, Epidemiology, and End Results program-Medicare data linked with the American Medical Association physician master file. The main outcome was receipt of genomic testing within 1 year of diagnosis as a function of physician-level factors. RESULTS: A total of 24,463 patients met the study criteria; they received care from 3172 surgeons and 2475 medical oncologists. Of 4124 tests ordered, 70% were ordered by a medical oncologist and 16% by a surgeon. In multivariable regression models, multiple variables were associated with receipt of testing, including having a medical oncologist (odds ratio [OR] 2.77; 95% CI 2.00-3.82), a surgeon specializing in surgical oncology (OR 1.20; 95% CI 1.09-1.31), and a female medical oncologist (OR 1.10; 95% CI 1.02-1.20). Having a medical oncologist with 5 or more years in practice was associated with lower odds of testing (OR 0.83; 95% CI 0.76-0.92). Surgical procedures performed at academic centers were associated with higher odds of testing (OR 1.11; 95% CI 1.02-1.20). CONCLUSIONS: Although most RS testing was ordered by medical oncologists, physicians in other specialties ordered roughly one-third of the tests. Physician characteristics, including gender and time in practice, were associated with receiving testing, creating opportunities for targeting interventions to help patients receive optimal care.

Breast Reconstruction: A Century of Controversies and Progress.

Breast cancer treatment has dramatically changed over the past century. Since Halsted's first description of radical mastectomy in 1882, breast reconstruction has evolved slowly from being considered as a useless or even dangerous procedure by surgeons to the possibility nowadays of reconstructing almost any kind of defect. In this review on the development of breast reconstruction, we outline the historical milestone innovations that led to the current management of the mastectomy defect in an attempt to understand the economic, social and psychological factors, which contributed to slow down its acceptance for several decades.

The Radicalization of Breast Cancer Surgery: Joseph Colt Bloodgood's Role in William Stewart Halsted's Legacy.

Johns Hopkins's surgeon William Stewart Halsted is renowned for popularizing the radical mastectomy, a disfiguring procedure that was overutilized during the 1900s. Cancer historians have questioned why Halsted, a meticulous surgical investigator, became more aggressive in his approach to breast cancer surgery when his own data failed to show prolonged patient survival. Joseph Colt Bloodgood, one of Halsted's early surgical residents, Hopkins's head of surgical pathology, and Halsted's primary outcome data analyst, played previously unrecognized roles. Bloodgood was an aggressive surgeon with a "lynch law" approach to breast lesions. As a surgical pathologist, Bloodgood was irrationally opposed to intraoperative frozen section diagnosis. Bloodgood's and Halsted's unwavering trust in each other created an environment where shared beliefs trumped surgical reality. However, after Halsted's death, Bloodgood recognized that they had been wrong and spent the rest of his life trying to reverse the progression while simultaneously "rewriting" details of his own involvement.

[History of breast cancer reconstruction treatment]. / Historique du traitement du cancer du sein.

The authors summarize in those six pages of drawings the history of breast cancer reconstruction treatment. The focus is on the variety of techniques available for breast reconstruction and on the debates around different indications.

Smoking and risk of breast cancer in the Generations Study cohort.

BACKGROUND: Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent. METHODS: We used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake. RESULTS: Among 102,927 women recruited 2003-2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03-1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08-1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07-1.41; P = 0.004) for starting smoking 1-4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12-1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96-1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001). CONCLUSIONS: Smoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease.

Three Newly-Discovered Copies of the Manuscript Mayaku Ko, Written by Shutei Nakagawa, with Special Reference to their Appearance and Genealogy.

Seishu Hanaoka's greatest achievement was the anesthetic Mafutsusan. He developed it and then used it successfully for various operations, primarily breast cancer tumor excisions. The developmental process can be traced in Mayaku Ko, a memorandum written and edited in 1796 by Hanaoka's close friend Shutei Nakagawa. Contained in this document is a list of fourteen prescriptions for earlier attempts by other doctors to create-a general anesthetic. These prescriptions, which Nakagawa had passed along to Hanaoka, were the foundation for the scientific breakthrough. The preface suggests that Hanaoka had nearly perfected Mafutsusan by 1796. Nakagawa's original manuscript has been lost, but copies of it are extant. Until recently, we knew of four, all of them in Japan. I have discovered three more: one in the University of Tokyo Library (Gakken Collection), another in the Keio University Shinanomachi Media Center, and the third in the Asahikawa Medical University Library (Sekiba-Samejima Collection). After carefully examiiing the new ones, I put the seven known copies of Mayaku Ko into four groups, A to D, according to the order in which they were likely transcribed. One of the copies in Group A, which is from the Matsuki Collection, appears to have been the first.

A Consideration on the Origin of Seishu Hanaoka's Nyugan-jun and Nyugan-jun Furoku.

Nyugan-jun is a manual that was used at Hanaoka's school, Shunrinken, describing two oral medicines and three ointments routinely administered after breast cancer surgery. Nyugan-jun Furoku is also a manual that was used at the school, depicting a variety of diseases of the breast, and oral concoctions to be administered. The earliest manuscript of both manuals was transcribed in February 1812. A manuscript of Ben-nyugansho narabini Chiho Soko, written by Ryozo Chiba in 1811, includes descriptions of an oral medicine and four ointments routinely given after breast cancer surgery. Although Choeito was only a common oral concoction in Nyugan-jun and Chiba's manuscript, the latter bears an original trace of Nyugan-jun. This indicates that Nyugan-jun and Nyugan-jun Furoku were completed by the end of February 1812, and their completion dates were not before August 1811.

The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations.

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913-1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations.

Impact of deprivation on breast cancer survival among women eligible for mammographic screening in the West Midlands (UK) and New South Wales (Australia): Women diagnosed 1997-2006.

Women diagnosed with breast cancer in the UK display marked differences in survival between categories defined by socio-economic deprivation. Timeliness of diagnosis is one of the possible explanations for these patterns. Women whose cancer is screen-detected are more likely to be diagnosed at an earlier stage. We examined deprivation and screening-specific survival in order to evaluate the role of early diagnosis upon deprivation-specific survival differences in the West Midlands (UK) and New South Wales (Australia). We estimated net survival for women aged 50-65 years at diagnosis and whom had been continuously eligible for screening from the age of 50. Records for 5,628 women in West Midlands (98.5% of those eligible, mean age at diagnosis 53.7 years) and 6,396 women in New South Wales (99.9% of those eligible, mean age at diagnosis 53.8 years). In New South Wales, survival was similar amongst affluent and deprived women, regardless of whether their cancer was screen-detected or not. In the West Midlands, there were large and persistent differences in survival between affluent and deprived women. Deprivation differences were similar between the screen-detected and non-screen detected groups. These differences are unlikely to be solely explained by artefact, or by patient or tumour factors. Further investigations into the timeliness and appropriateness of the treatments received by women with breast cancer across the social spectrum in the UK are warranted.

Are international differences in breast cancer survival between Australia and the UK present amongst both screen-detected women and non-screen-detected women? survival estimates for women diagnosed in West Midlands and New South Wales 1997-2006.

We examined survival in screened-detected and non-screen-detected women diagnosed in the West Midlands (UK) and New South Wales (Australia) in order to evaluate whether international differences in survival are related to early diagnosis, or to other factors relating to the healthcare women receive. Data for women aged 50 - 65 years who had been eligible for screening from 50 years were examined. Data for 5,628 women in West Midlands and 6,396 women in New South Wales were linked to screening service records (mean age at diagnosis 53.7 years). We estimated net survival and modelled the excess hazard ratio of breast cancer death by screening status. Survival was lower for women in the West Midlands than in New South Wales (5-year net survival 90.9% [95% CI 89.9%-91.7%] compared with 93.4% [95% CI 92.6%-94.1%], respectively). The difference was greater between the two populations of non-screen-detected women (4.9%) compared to between screen-detected women, (1.8% after adjustment for lead-time and over-diagnosis). The adjusted excess hazard ratio of breast cancer death for West Midlands compared with New South Wales was greater in the non-screen-detected group (EHR 2.00, 95% CI 1.70 - 2.31) but not significantly different to that for women whose cancer had been screen-detected (EHR 1.72, 95% CI 0.87 - 2.56). In this study more than one in three breast cancer deaths in the West Midlands would have been avoided if survival had been the same as in New South Wales. The possibility that women in the UK receive poorer treatment is an important potential explanation which should be examined with care.

Understanding and effectively addressing breast cancer in African American women: Unpacking the social context.

Black women have a higher incidence of breast cancer before the age of 40 years, more severe disease at all ages, and an elevated mortality risk in comparison with white women. There is limited understanding of the contribution of social factors to these patterns. Elucidating the role of the social determinants of health in breast cancer disparities requires greater attention to how risk factors for breast cancer unfold over the lifecourse and to the complex ways in which socioeconomic status and racism shape exposure to psychosocial, physical, chemical, and other individual and community-level assaults that increase the risk of breast cancer. Research that takes seriously the social context in which black women live is also needed to maximize the opportunities to prevent breast cancer in this underserved group. Cancer 2016;122:2138-49. © 2016 American Cancer Society.