Journal of the National Cancer Institute

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1 2013 Media Kit Advertising & Sales Contacts Allan Kolstein Corporate Account Manager e: For supplements, reprints, eprints or tailored products: e: ISSN (Print) The () is internationally acclaimed as the source for the most up-to-date news and information from the rapidly changing fields of cancer research and treatment. For the past several years, the has been ranked as one of the mostcited original-research cancer journals by the Institute of Scientific Information in its annual Journal Citation Reports. The journal is read by leading oncologists, internists, surgeons, cancer researchers, epidemiologists, and policy makers. Useful Information Print Circulation: 1,300 Geographic Breakdown: North America 60% - Europe 20% - Rest of World 20% Average Monthly Page Views: 332,600 Frequency: 24 Average Monthly Uniques: 108,532 Peer Reviewed: Yes Average Available Ad Impressions: 137,848* *Combined monthly leaderboard and skyscraper positions Editor-In-Chief: Carmen J. Allegra No. of etoc Subscribers: 6,442 Impact Factor: Ranking: 6/194 Si: Oncology Journal Citation Reports (Science Citation Index, ISI) Target Audience: Oncologists

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3 ISSN (Print) ISSN (Print) American Journal of Epidemiology Vol. 176, No. 6 The Author Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of DOI: /aje/kws214 American Public Journal Health. of Epidemiology All rights reserved. For permissions, please journals.permissions@oup.com. Advance Vol. Access 176, No. publication: 6 The Author Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of DOI: /aje/kws214 July 25, 2012 DOI: /jnci/djs327 Published by Oxford University Press Public Health. All rights reserved. For permissions, please journals.permissions@oup.com. Advance Access publication on August 20, Advance Access publication: July 25, 2012 Invited Commentary Article Invited Commentary Invited Commentary: Assessing Mechanistic Interaction Between Coinfecting Pathogens for Diarrheal Disease relationship Invited Commentary: Between Assessing Mammographic Mechanistic Interaction Density Between and Breast Coinfecting cancer Pathogens Death for Diarrheal in the Disease Breast cancer Surveillance consortium Gretchen L. Gierach, Laura Ichikawa, Karla Kerlikowske, Louise A. Brinton, Ghada N. Farhat, Pamela M. Vacek, Donald L. Weaver, Catherine Schairer, Stephen H. Taplin, Mark E. Sherman Tyler J. VanderWeele* Manuscript received December 06, 2011; revised June 18, 2012; accepted June 22, Tyler* J. Correspondence VanderWeele* to Dr. Tyler J. VanderWeele, Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Correspondence 677 Huntington to: Gretchen Avenue, L. Gierach, Boston, PhD, MPH, MA Executive ( Blvd, tvanderw@hsph.harvard.edu). Ste 550, Rm 5016, Rockville, MD ( gierachg@mail.nih.gov). * Correspondence to Dr. Tyler J. VanderWeele, Departments of Epidemiology and Biostatistics, Harvard School of Public Health, 677 Huntington Initially submitted Avenue, Boston, MarchMA 1, ; ( accepted tvanderw@hsph.harvard.edu). for publication March 9, Background Women with elevated mammographic density have an increased risk of developing breast cancer. However, Initially submitted March 1, 2012; accepted for publication March 9, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent The interaction of other estimates factors. from Bhavnani et al. (Am J Epidemiol. 2012;176(5): ) are used to evaluate evidence for mechanistic interaction between coinfecting pathogens for diarrheal disease. Mechanistic interaction interaction evaluated Methods TheWe is said to estimates relationships be present from between if Bhavnani there mammographic are individuals et al. (Am Jdensity for Epidemiol. whom and the risk 2012;176(5): ) outcome of death from would breast occur cancer are if both used and of all to 2 causes exposures evaluate are evidence within present for the mechanistic but US would Breast not Cancer interaction occur Surveillance if 1between or theconsortium. other coinfecting of thewe exposures pathogens studied 9232 isfor absent. women diarrheal diagnosed In the disease. epidemiologic with Mechanistic primary literature, invasive interaction isbreast nistic said interaction carcinoma to be present during is often if there , conceived are individuals with of as a mean synergism for follow-up whomwithin theof outcome 6.6 Rothman s years. would Mammographic sufficient-cause occur if both density framework. of 2was exposures assessed Testsare for addi- mecha- present using tivebut interaction the would Breast not are Imaging occur sometimes ifreporting 1 the used other and todata assess of the System exposures such(bi-rads) synergism absent. density or mechanistic In classification. the epidemiologic interaction, Hazard ratios literature, but testing (HRs) mechanistic95% interaction additive confidence interaction is often intervals conceived only(cis) allows were of as for estimated synergism the conclusion by within Cox proportional of Rothman s mechanistic hazards sufficient-cause interaction regression; under framework. women fairly with strong Tests scattered monotonicity for addi- and for positive tive interaction fibroglandular assumptions. are sometimes densities Alternative (BI-RADS used tests to for 2) assess were mechanistic the such referent synergism interaction, group. All or which statistical mechanistic do not tests require interaction, were two-sided. monotonicity but testing assumptions, for positive have additive been interaction developed onlymore allows recently for thebut conclusion require more of mechanistic substantial interaction additive interaction under fairly to draw strong the monotonicity conclusion of the Results A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age assumptions. presencealternative of mechanistic tests for interaction. mechanistic Theinteraction, additive interaction which doreported not require by monotonicity Bhavnani et al. assumptions, is of sufficient havemagni- tude developed to provide morestrong recently evidence but require of mechanistic more substantial interaction additive between interaction rotavirustoand draw Giardia the conclusion and between of the rotavirus at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, been presence and of and Escherichia. mechanistic income), high coli/shigellae, interaction. density (BI-RADS The evenadditive 4) was withoutinteraction not related any assumptions reported to risk of about by death Bhavnani from breast monotonicity. et al. cancer is of (HR sufficient = 0.92, magnitude to CI = provide 0.71 to strong 1.19) or evidence death from ofall mechanistic causes (HR = interaction 0.83, 95% CI between = 0.68 to rotavirus 1.02). Analyses and Giardia stratified and by between stage and rotavirus other 95% and Escherichia. prognostic coinfectingfactors pathogens; coli/shigellae, yielded diarrhea; similar evenresults, without interaction; except any assumptions mechanism; for increased about synergism risk monotonicity. of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0 cm coinfecting (HR = 1.55, pathogens; 95% CI = diarrhea; 1.14 to 2.09). interaction; mechanism; synergism Conclusions Abbreviations: High mammographic CI, confidencebreast interval; density ICR, was interaction not associated contrast with ratio; risk RERI, of death relative from excess breast cancer risk due or death to interaction; from any RR, relative risk. cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast Abbreviations: CI, confidence interval; ICR, interaction contrast ratio; RERI, relative excess risk due to interaction; RR, relative risk. cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed. J Natl Cancer Inst 2012;104: In their paper, Bhavnani et al. (1) have presented strong is j. For now, for simplicity, we assume that there is no confounding for the effects of the exposures on the outcome, but evidence of interaction, of a fairly substantial magnitude, In their between paper, different Bhavnani coinfecting et al. (1) have pathogens presentedfor strong diarrhealis j. For wenow, will for return simplicity, to this assumption we assume that later. there Additive is no interaction con- with using for breast risks the effects cancers wouldof associated typically the exposures with be low assessed on density, the outcome, by (p 11 but p 00) elevated evidence mammographic disease. of interaction, Specifically, density of is they one a fairly of report the substantial strongest positiverisk additive magnitude, factors and Compared mul-foundintiplicative different breast interaction cancer coinfecting (1). mammographic between pathogens rotavirus density for (referred anddiarrheal Giardia cancers andwe arising will {(p return dense 10 p 00)+(p tobreasts this 01 assumption often p 00)}, demonstrate which later. can Additive adverse be rewritten interaction as for between non familial to disease. herein between density ) Specifically, rotavirus reflects they and the report tissue Escherichia composition positivecoli/shigellae. additive of the breast and multiplicative projected report on interaction a two-dimensional positive between additive mammographic rotavirus and multiplicative and image: Giardia higher interaction and positive lymph {(p 10 nodes, p 00)+(p lymphatic 01 or p 00)}, vascular p11which invasion, p10can p01 be and þrewritten advanced p00: as ð1þ They prognostic alsousing features, risks including wouldlarger typically size, higher be assessed histological by grade, (p 11 p 00) as relative between adipose between rotavirus content Giardia and corresponds Escherichia and E. to coli/shigellae, lower coli/shigellae. measured although density They also stage in this (4 10). Neither the reasons underlying the association of This quantity assesses whether the effect of the 2 exposures reportcase, positive neitheradditive nor and multiplicative interaction p11 p10 p01 þ p00: ð1þ because adipose tissue is radiolucent. Conversely, breasts composed is high statistically proportion Giardia significant. of fibroglandular E. In this coli/shigellae, invited tissue have commentary, higher although measured the in this evidence for its associations This quantity with more density with increased breast cancer risk nor those accounting together exceeds the sum of their effects considered separately. Ifassesses aggressive of a between higher the interaction whether tumor contrast thecharacteristics effect above of theare greater 2 exposures than 0, the density. case, high neither for mechanistic density additive related nor interaction to multiplicative breast between cancer interaction risk these factors, coinfecting such is statisticallyogens significant. a positive is evaluated family In thishistory by invited using of commentary, breast the results cancer, of and their meno- evidence analyses. tissue correspond rately. negative. Ifto the radiologically interaction Sometimes, dense contrast instead, areas above [reviewed a ratio is greater measure in (11)]. than is used 0, the to eval- completely path-together understood. additive exceeds interaction microscopic the sumis regions of said their to of be effects fibroglandular positive; considered if less than sepa- 0, then as nulliparity, pausal for hormone mechanistic therapy interaction use; yet studies between consistently these coinfecting demonstrate pathogens compared is evaluated by using the results of their analyses. however, additive several uate studies interaction additive (12 15) interaction. is said have to reported beif positive; wethat divide the ifabsolute the lessinteraction than 0, then contrast that, ASSESSING with low density, MECHANISTIC high density INTERACTION confers relative risks amount of negative. radiologically above Sometimes, bydense p00, area we instead, is obtain less predictive aaratio quantity measure of risk sometimes than is the used to referred evaluate of the additive the breast relative interaction. composed excess of If dense risk wedue tissue, divide to suggesting interaction the that (RERI) contrast (2, 3) or to as (rrs) of four- to fivefold for breast cancer, independent of these and proportion other ASSESSING factors Suppose [reviewed MECHANISTIC that in (1)]. wealthough haveinteraction 2high binary density exposures may contribute to delayed outcome detection and because that weof let radiologic pij denote masking theof probability tumors to of the the risk the associated relative with excess mammographic risk due to density. interaction (RERI) (2, 3) or and aboth binary dense above and the nondense by interaction p00, we radiological obtain contrasta components quantity ratio (ICR): sometimes may contribute referred to as by dense Suppose outcome tissue, reduced that when wemammographic have the first 2 binary exposure sensitivity exposures is i and alone the and does second anot binary exposure Although the data interaction have consistently contrast RERIratio demonstrated ¼ RR11 (ICR): RR10 that high RR01 density þ 1; explain outcome the increased and that breast wecancer let pij risk denote associated thewith probability high density of the increases risk of breast cancer, it is unclear whether breast cancer outcome when the first exposure is i and the second exposure RERI ¼ RR11 RR10 RR01 þ 1; (2). In fact, the association between density and risk persists over patients with 396high density are at increased Amrisk J of Epidemiol. death from 2012;176(6): breast extended periods and with repeated screening [reviewed in (3)]. cancer compared with those with low density, after adjusting for 396 Am J Epidemiol. 2012;176(6): Articles Vol. 104, Issue 16 August 22, 2012 Print Advertising Options & Rates Display Rates x 3x 6x 12x 18x 24x Special Position Premiums Full Page $2560 $2500 $2435 $2305 $2180 $2050 Full Page $4290 $4230 $4165 $4035 $3910 $3780 ½ Page $1600 $1560 $1520 $1440 $1360 $1280 ½ Page $3330 $3290 $3250 $3170 $3090 $3010 ¼ Page $1105 $1080 $1050 $1000 $940 $885 Cover 4-50% Cover 2-40% Cover 3-10% Facing Leading Article 10% ¼ Page $2835 $2810 $2780 $2730 $2670 $2615 Facing Contents 10% Double Page Spread = 2 x Full page rate Incentives Publisher s Discount 10% Agency Commission 15% More options and solutions in partnership with Downloaded from at OUP site access on August 30, 2012 Downloaded from at OUP site access on August 29, 2012 Downloaded from at OUP site access on August 29, 2012 Loose and Bound Inserts available Belly Band Sponsored supplements published and distributed with the journal Article reprints and eprints useful as conference handouts

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