text:
Randy 'Duke' Cunningham
Imprisoned Cunningham outlines depths of corruption to FBI
8:53 p.m. July 17, 2007
WASHINGTON – In two days of prison interviews with federal agents this year, disgraced former Rep. Randy "Duke" Cunningham described a level of corruption on his part more extensive than previously known and dealt a potentially devastating blow to the defense being waged by one of the defense contractors alleged to have bribed him.
The interviews were conducted in February at the federal prison near Tucson, where the longtime Republican congressman is serving an eight-year and four-month sentence after admitting to accepting more than $2.4 million in bribes. He pleaded guilty to conspiracy and tax evasion.
Cunningham's answers are bad news for Brent Wilkes, president of Poway-based ADCS Inc., who is fighting bribery charges against him. They set the stage for what could be a dramatic courtroom showdown between the former North County congressman and his longtime benefactor.
Wilkes faces 30 counts in two separate indictments, including charges that he gave Cunningham $600,000 in gifts and cash in exchange for Cunningham's help in getting more than $80 million in defense contracts. Wilkes' two trials are expected to occur this fall. The government has not said if it will bring Cunningham back to San Diego to testify.
Cunningham was able to promote defense contracts for favored companies through the use of legislative "earmarks," provisions lawmakers could slip anonymously into spending bills without debate, discussion or disclosure that benefit interests in their districts or their political supporters Wilkes has said a $100,000 payment he made to Cunningham in 2000, was not a bribe, but instead was to purchase Cunningham's river yacht, the Kelly C.
"Cunningham said that there was never a sale," said the FBI report. "Cunningham stated that he and Wilkes created the cover story of a boat sale to explain, if anyone ever found out and asked, his receipt of $100,000 from Wilkes." Cunningham told investigators that Wilkes fully understood that there would be "no actual change in ownership" of the yacht. The two men agreed to divide the $100,000 into two checks because both "felt that the smaller checks might be less noticeable."
The documents show that Cunningham had first asked Wilkes for $550,000.
"Wilkes said no to the $550,000 but then countered with an offer of $100,000 if Cunningham would ensure that the support and earmarks would continue to happen. Cunningham promised Wilkes that he would 'fight like hell' for Wilkes/ADCS."
The FBI report made the point that Cunningham was clear about the quid pro quo:
"Cunningham stated that, by 2000, he had already been receiving numerous benefits from Wilkes that included such things as vacation trips, liquor, cash/maintenance money . According to Cunningham, in return for these benefits, he had been helping Wilkes/ADCS in their efforts to secure government contracts."
Phone messages left at Wilkes' attorneys' offices Tuesday night were not returned.
His admissions are very much at odds with the image that Cunningham tried to create after his downfall. In a letter made public and in private statements to friends, he portrayed himself as someone unable to withstand the blandishments of corrupt contractors and someone who merely accepted "gifts" but never sold his office.
His admissions to the investigators – who were from the FBI, the Internal Revenue Service, the U.S. attorneys' office and the Defense Criminal Investigative Service – also shed light on the actions of others implicated in the scandal.
They include Mitchell Wade, president of MZM, Inc. in Washington, who pleaded guilty in the case but has not yet been sentenced, and Thomas Kontogiannis, a New York developer accused of laundering the bribe money.
Kontogiannis pleaded guilty to providing $1.1 million in mortgages to Cunningham for a Rancho Santa Fe mansion, even though he knew the house was purchased with proceeds from illegal activity. The plea was made in February but was not made public until last month.
According to the FBI summary, Cunningham admits to being provided with prostitutes, misleading congressional ethics officials, making others buy gifts for his daughters, personally devising the schemes to launder his bribes, lying to his staff, and putting unrelenting pressure on government officials who thought the defense contracts he pushed with congressional earmarks were wasteful.
Cunningham was well placed steer military intelligence contracts toWilkes and Wade because he was on the House defense appropriations subcommitteeand the House Permanent Select Committee on Intelligence.
He also told investigators he demanded regular cash payments – he called them "maintenance money" – once even summoning one of his bribers to his office at the U.S. Capitol to give him $3,000 in cash.
In addition to the FBI summary of the prison interviews with Cunningham, Copley News Service obtained a 75-page affidavit filed by the FBI in support of a search warrant in the case. It provides glimpses of what investigators found as they built their case against Cunningham and those the suspected of conspiring with him.
The FBI stated that:
More than $1 million in bribes were laundered by being sent to Kontogiannis instead of going directly to Cunningham. Investigators identified at least 70 separate bank accounts maintained by Kontogiannis at only one bank.
Despite all his many businesses, Kontogiannis has not filed a tax return since 2001.
For the first time, investigators shed light on what Kontogiannis expected to get from Cunningham – help on a potential sale of fighter jets to his native Greece.
The Rolls Royce that drew so much attention early in the investigation was not the only car that Cunningham made the contractors buy for him. In only two days in early 2002, the congressman bought a $43,000 Thunderbird and a $41,000 BMW from Bob Baker Ford in San Diego with $63,000 of his payment coming from bribes. That was three months before Wade gave him $10,000 toward the used Rolls Royce.
In mid-2004 when Cunningham needed to make repairs to his boat, he called Wade and demanded $6,500 cash. Wade took the money out of his petty cash, stuffed the cash into a bulging envelope and rushed it over to a Cunningham fundraiser at a Washington restaurant, giving it to a Cunningham staffer.
In his prison interviews with investigators, as summarized by the FBI, the former congressman is reported to have:
Insisted there were no prostitutes at Wilkes' Washington poker games, but said Wilkes hired prostitutes for him during a Hawaii vacation. Cunningham was miffed that Wilkes got the "younger and cuter" prostitute and said he was "somewhat embarrassed on this occasion because he had some difficulty in completing intercourse." On the next night, Cunningham again had a prostitute but said he "did not have sex" with her "because he felt guilty about his behavior."
Said that among the many weapons Wade bought him was a Glock handgun, which he kept in a box on his boat – in apparently violation of D.C. laws.
Said he tried to make peace between Wade and Wilkes when the two former friends fought over contracts.
Openly "recalled exerting pressure on government officials" to reward his bribers.
Said Wilkes told him he was "hiding money in a bank account in Panama" to pay him bribes.
The FBI document also said Cunningham admitted to investigators he: Oversaw attempts to hide his bribe-taking in case he was ever caught.
Made Wilkes buy Cunningham's daughter a computer when she went to college and then pay for its later repair.
Made either Wilkes or Wade pay his way to the 2003 Super Bowl, Jimmy Buffet concerts in Chula Vista, and several Washington Wizards and Redskins games.
Had to find ways to get around objections from Sen. Richard Shelby, R-Ala., and Rep. Duncan Hunter, R-El Cajon, both of whom tried to block Cunningham's spending projects for Wade and Wilkes as wasteful and unneeded.


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Frankel: 'I had what counted the most. I had you.'UPDATED 10:50 PM EST Nov 06, 2012
Lois Frankel thanks her family, supporters and opponent Adam Hasner in her victory speech after winning a seat in Congress.
More Video
CommentsThe views expressed are not those of this site, this station or its affiliated companies. By posting your comments you agree to accept our terms of use.blog comments powered by Disqus

subset: commoncrawl


text: 1 Review 1 Ratings French Onion Dip Most Helpful Newest Highest Rating This really was an excelent dip!!I had my sister and her 2 daughters here and they ate every DROP!! Very Good !!! 5 people found this helpful. Was it helpful to you? [Yes] [No] Theresa P March 28, 2003 Show More Reviews Back To Top French Onion Dip


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Separate names with a comma.
Thanks for the quick response everyone, my phone came with 444 installed. Got it new from amazon, I will go ahead and update.
Thanks again.
Hi everyone, I just got my moto x and want to know if I should update it. l seen a few bad post about lolly pop causeing problems with this...
htc 1
Not enough change to get me excited.
Who cares anymore!!
Way to much hype and drama for what it is:blink: Samsung jumped the shark
Thanks timmy worked perfect:hail:
No luck same result, do i need to unroot and then reroot and start all over??
my safestrap seams to have gone south on me, today i could not toggle to safe mode. first problem as it has been great. any way to fix?
I install safestrap as directed on my bionic but when i reboot i press menu and it just reboots
droid will not go past logo , also tryed from keyboard and can not get into recovery. Please help.
advanced task killer is your problem, get rid of it!!!!!
OP how do you get an upgrade so soon??
Looks like the apple deal is about rapped up for Jan as well.
Thanks everyone for the help:)
My wife's droid went nuts on her, stuff keeps droping off her sd card, even files that were backed up now install as if it was a clean install and...
That was itdancedroidreboot
I went in there and changed text to white but it remains black. I changed item time and item text?:icon_eek:
How do you change the clock time to white??


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Custom Character
One question in bacta where you create your character and when you purchase all characters why isn't sowing Emperor's torso Vader's torso Scouttrooper helmet and Stormtrooper torso also why vader isn't breathing like in the Story play :lightning
Because once again, LA did a half arsed job and didnt add everything in...
Oh come on you have to be kiding me right?
yes i noticed this its just the creators travlers tales got lazy on that or they might have just rushed to finish this game
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Victoria Crime Stoppers: Searching for wanted person
Oct. 22, 2012 at 5:22 a.m.
Oct. 22, 2012 at 5:22 a.m.
Crime Stoppers pays: 361-572-4200
Wanted Person: Marcel Ernest Poirrier III has an outstanding warrant for his arrest. The warrant is for violation of probation on the original charge of possession of controlled substance Penalty Group 2. Poirrier is 45-year-old man who is 5 feet 9 inches tall.
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News Archive
Podcast: April 2010 exhibitions
In a monthly series Finn Grey '10 speaks with PNCA students, faculty and alumni exhibiting in Portland and beyond. This month, Grey interviews Lydia Rosenberg '10, whose work will be in the BFA Gallery through the month of April.
Finn Grey '10 Interviews Lydia Rosenberg '10
Download audio (5 MB, MP3)
Podcast | PDXplore: Crossing the Columbia River
The Architecture Foundation of Oregon (AFO) and designers from PDXplore present Crossing the Columbia River: What Does it Mean for Our Region?, a two-phase forum in February and March 2010 at PNCA. Featuring exhibitions and public programs, the forum drew attention to the current status of the Columbia River Crossing, increasing citizens' recognition of the project's profound scope and impact, and inspiring broad discussion about its potential for excellence. For more information about the forum, visit the "Architectural Foundation of Oregon":http://www.af-oregon.org/ or the "PDXplore web site":http://www.pdxplore.org
Columbia River Crossing: An evening with members of the CRC Project Team
Representatives from the Columbia River Crossing and the cities of Portland and Vancouver detailed progress made thus far on the project and discussed next steps. The panel spoke about the efforts being made to improve safety, extend light rail, add bicycle/pedestrian paths and support smart community growth. CRC staff also reported how community input has thus far informed bridge, transit and interchange designs.
International Panel: Fresh Design Perspectives
Moderator Ethan Seltzer led a provocative discussion about the Columbia River Crossing with international experts in the fields of design, culture and urban planning. Panelists included: Boston Globe architecture critic Robert Campbell, artist Ed Carpenter, outgoing National Endowment for the Arts Director of Design Maurice Cox, and Toronto architect and urban design consultant Ken Greenberg.
Photos by Ingrid Hain '13.
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Registration continues for fall semester credit courses at East Central College.
Cookie Hays, vice president of student development, encourages everyone who is considering enrollment to contact the college as soon as possible to start the registration process.
You must login to view the full content on this page.
Or, use your linked account:


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Yale University — New Asia College (YUNA) Exchange
The YUNA Exchange matches eight students from Yale University with eight students from New Asia College at The Chinese University of Hong Kong for a unique six-month, themed, academic and cultural exchange program. Yale participants plan a two-week visit in New Haven, travel to Hong Kong over Yale's spring break, and conduct research on the theme. Many students cite YUNA as one of the most important experiences of their time at Yale, both for the personal growth it allows and for the friendships that are formed through the program.
*Photography by Wong Yam Ling and Annie Lin
Applications for 2016-2017 YUNA Exchange available in September
The theme for the 2015-2016 YUNA Exchange was National Identity and Citizenship.
This January, the Hong Kong students arrived to New Haven, bundled in new ski coats. YUNA commenced with a seasonal turkey dinner, and proceeded to open lectures and symposiums across Yale. The delegation traveled NYC and Boston to study urban history and monuments of immigration. Come March, the New Haven students flew to Hong Kong sporting T-shirts. The trip highlighted munching street snacks and widely exploring the metropolitan hubbub of the multilingual islands. The final symposium took place overlooking the glass waters of the Chinese University of Hong Kong. The delegation will be in charge of nominating the theme of next year's exchange trip.
Yale-China will begin accepting applications for the 2016-2017 YUNA Exchange in fall 2016. Check back for updates! more>
Info sessions will be held in September; check back here for times and locations. You can also view our Virtual Info Session.
Program Legacy
YUNA is one of the programs that best embody the six decade long partnership between the Yale-China Association and New Asia College. For more than twenty years, the program has brought some of the brightest and most curious students from Yale and from New Asia together to explore shared issues in very different cultures. Recent themes have included Sovereignty and Society; Migration and Cultural Integration; Innovation, Creativity, and Social Change; Capitalism and Society; and Social Justice.
From the Field
"Participating in the YUNA program has been one of the most formative experiences of my Yale career. When I first heard about the program, I likened it to the other spring break opportunities circulating Yale's campus—exciting and well-intentioned, but ultimately nothing more than a glorified tourist trip. From the get-go, YUNA defied my pre-conceived notions, allowing me the opportunity to holistically engage with cultural customs beyond my comfort zone. YUNA's unique reciprocity—having the HK-ers come to Yale and then us to Hong Kong—made the program much more substantial than a simple voluntourism trip." – Christofer Rodelo, YUNA 2014 more >


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Mantle cell lymphoma with aberrant expression of CD10
Version of Record online: 28 JUN 2008
DOI: 10.1111/j.1365-2559.2008.03060.x
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Limited
Volume 53, Issue 1, pages 20–29, July 2008
Additional Information
How to Cite
Zanetto, U., Dong, H., Huang, Y., Zhang, K., Narbaitz, M., Sapia, S., Kostopoulos, I., Liu, H., Du, M.-Q. and Bacon, C. M. (2008), Mantle cell lymphoma with aberrant expression of CD10. Histopathology, 53: 20–29. doi: 10.1111/j.1365-2559.2008.03060.x
Publication History
- Issue online: 28 JUN 2008
- Version of Record online: 28 JUN 2008
- Date of submission 13 December 2007 Accepted for publication 25 January 2008
- Abstract
- Article
- References
- Cited By
- Bcl-6;
- genetics;
- immunohistochemistry;
- mantle cell lymphoma
Aims: Morphological, immunophenotypic and genetic heterogeneity amongst mantle cell lymphomas (MCLs) can lead to difficulties in diagnosis and management. The aim was to describe the clinical and pathological features of MCLs with aberrant expression of CD10.
Methods and results: Of 17 specimens from 13 patients, 14 expressed CD10 and three (presenting before or after a CD10+ specimen) did not. All expressed cyclin D1 and carried the t(11;14)(q13;q32)/CCND1-IGH translocation. Similar to non-selected MCL patients, most patients had disseminated disease and an adverse clinical course. Five specimens showed pleomorphic blastoid morphology and blastoid transformation was associated with a change in phenotype, including gain or loss of CD10. Additional phenotypic variations likely to cause diagnostic difficulty were present in eight specimens: five were CD5− and five (all CD10+) expressed Bcl-6. One Bcl-6+ case carried a BCL-6 translocation and three others had extra copies of the BCL-6 gene. Sequence analysis of the immunoglobulin heavy chain variable region in five cases showed only one to have low-level somatic mutation, indicating that they did not arise from germinal centre B cells.
Conclusions: Expression of CD10 by MCL is often associated with other variant morphological, immunophenotypic or genetic features, but does not reflect derivation from germinal centre B cells.


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The Provost's Office handles vital issues such as: academic budget priorities and requests, academic programming initiatives, as well as faculty and staff concerns which include recruitment, promotion, and tenure. The Provost works closely with the Faculty Senate and the Provost's Council on these issues.
What's New?
- Please welcome Dr. Karen Carey. She is here!
- Congratulations to our Faculty Excellence Awards recipients!
Dr. Karen Carey, Provost
11120 Glacier Hwy
Juneau, AK
Mailstop: HB1
Provost's Office
- 907-796-6486 (Information)
- 907-796-6040 (Fax)
11120 Glacier Hwy
Juneau, AK
Mailstop: HB1


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Ryan vs. Dorkman
Ryan vs. Dorkman, often abbreviated by fans as RvD, is a series of Star Wars fan films, created by Ryan Wieber and Michael "Dorkman" Scott, and first released to the internet on March 1, 2003.
Ryan vs. Dorkman[edit]
|Ryan vs. Dorkman
|Directed by
|Michael Scott
Ryan Wieber
|Written by
|Ryan Wieber
Michael Dorkman Scott
|Ryan Wieber
Michael Dorkman Scott
|Distributed by
Release dates
|March 1, 2003
Ryan vs. Dorkman was produced as an entry in a lightsaber choreography competition hosted by TheForce.net, a prominent Star Wars fan site noted for its fan film-making community. According to the official TFN entry for the film, the backstory involves Ryan and Michael, or "Ryan_W" and "DorkmanScott" as they are known on TheForce.net's forums, meeting after their friendly online rivalry over who is the better saber artist escalates too far. The fight to the death will determine once and for all who is the most skilled with a saber.[1]
In mid-2006, the short became a viral video after being posted on such websites as eBaumsworld, CollegeHumor, and the front page of YouTube as a "Featured Video." The YouTube video officially surpassed one million views on January 30, 2007, along with tens of thousands of hits at other sites.[citation needed]
As of July 2016, the original RvD had surpassed 7 million views on YouTube. A version of the film uploaded to Google Video also surpassed two million views.[citation needed]
In early 2008 Wieber and Scott re-mastered "RvD" and made it available for download on the official site. The re-mastering involved removing the "greenish-yellow wash," re-doing some effects, fixing rotoscoping errors, reversing the effects from the de-interlacing (which gave diagonal lines a "jagged" look), re-framing certain cuts and upgrading the audio track from a loud mono track to a softer stereo track. A more detailed explanation of the remastering process is also available on the site.[citation needed]
Both Ryan and 'Dorkman' were featured in the music video for Weezer's 2008 song "Pork and Beans" which included many other internet video stars.[2]
Ryan vs. Dorkman 2[edit]
|Ryan vs. Dorkman 2
|Directed by
|Michael Scott, Ryan Wieber
|Written by
|Ryan Wieber
Michael "Dorkman" Scott
|Ryan Wieber
Michael "Dorkman" Scott
|Music by
|Gordy Haab
Kyle Newmaster
Release dates
|February 24, 2007
Wieber and Scott announced in May 2006 that they would be producing a sequel. Ryan vs. Dorkman 2 (RvD2) was shot in Atlanta, Georgia in August 2006, and featured several technical improvements over the original RvD, such as the fact that it was shot in 24p high-definition, as opposed to the original's 30p standard definition. The lightsaber blades also interact with the environment in the form of sparks, burns and other effects which were not present in the original.[citation needed]
The film's score was recorded with a 57 piece orchestra at Capitol Studios in Hollywood. To accomplish this goal, film composers Gordy Haab and Kyle Newmaster donated their time and talents to the project.[3] The film's creators solicited donations from fans in order to pay the musicians. M.B Gordy (lead percussionist from Battlestar Galactica) provided the percussion.
The film premiered February 24, 2007 at the Wilshire Fine Arts Theatre in Los Angeles,[4] with a screening at the New York Comic Con the following day. The film was released on the internet on March 1, 2007, with a soundtrack DC release later that summer. As of July 2016, the official version on YouTube has over 1 million views.[citation needed]
The film was entered into the 2008 Star Wars Fan Movie Challenge, where it won Best Visual Effects.[5]
On December 19, 2008, RvD2 was re-released in full HD on YouTube's new widescreen player. As of July 2016 this new version had passed 1,000,000 views.[citation needed]
In August 2010, Time magazine listed it as one of the Top 10 Star Wars fanfilms.[6]
Ryan vs. Dorkman 3[edit]
In a behind the scenes video from Wieber and Scott, they commented on possible plans to do a Ryan vs. Dorkman 3 sometime in the future. No official timetable has been set, but Wieber and Scott claim that they will do it when they obtain more ideas on how they want the third battle to shape up. They have further stated that while they could make a third lightsaber battle now, it would basically be considered a "clone" of RvD2 with no real advancement in special effects and filmmaking.[7] In October, 2014, Michael Scott was injured by a car accident,[8] and as of December is still hospitalized,[9] though making progress. This leaves the fate of Ryan vs. Dorkman 3 unknown. Michael Scott has recovered from his injuries, but may never rehabilitate to his previous physical or mental condition.
- ^ "TFN FanFilms - FX Projects - Ryan vs. Dorkman". Retrieved March 12, 2010.
- ^ "Weezer Gives Web Celeb Tribute in Vid". StarWars.com. May 23, 2008. Retrieved March 12, 2010.
- ^ Schatanoff, David (February 27, 2007). "Kyle Newmaster and Gordy Haab – Composers – Star Wars Fanatics". The Alternakids. Retrieved March 12, 2010.
- ^ Young, Clive (February 19, 2007). "Ryan Vs. Dorkman II Premieres Saturday". Fan Cinema Today. Retrieved March 12, 2010.
- ^ "And the real winners are...". San Diego Union-Tribune. July 25, 2008. Retrieved March 12, 2010.
- ^ "The Top 10 Star Wars Fan Films", Time, August 24, 2010, retrieved September 15, 2010
- ^ "RvD2 - FAQs (Part 5)". May 31, 2007. Retrieved March 12, 2010.
- ^ "VFX artist Michael Scott injured in car accident". October 3, 2014. Retrieved December 7, 2014.
- ^ "Support Dorkman Scott". Retrieved December 7, 2014.
External links[edit]
- Official home page
- Ryan vs. Dorkman at the Internet Movie Database
- Ryan vs. Dorkman 2 at the Internet Movie Database
- Interview with Ryan and Dorkman on Geekza.


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Alexandria Gazette
From Wikipedia, the free encyclopedia
The Alexandria Gazette was a succession of newspapers based in Alexandria, Virginia, United States. The newspaper offers an important source of information for events in Alexandria, particularly in the nineteenth century.
The newspaper was established on February 5, 1784 by George Richard & Company as the Virginia Journal. The Alexandria Gazette building was located at 317 King Street.
A successor to the earlier iterations ran as a daily newspaper from 1834 to 1974.[1] Its first publisher was Edgar Snowden.[1]
- ^ a b "Alexandria Gazette". Chronicling America. Library of Congress. Retrieved 21 March 2014.
External links[edit]
|This article about a Virginia newspaper is a stub. You can help Wikipedia by expanding it.


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I run a membership site using WP 2.x and I'd like to be able to allow each registered user to upload a photo of themselves. Note: I don't want to use Avartars.
I've searched high and low for a solution that would enable me to add an Upload facility to the user profile page. There appear to be quite a few WP image plugins out there - but none of them provide this exact functionality.
There are those like the excellent Userextra/Usermeta by James Ponder that extend WP's profile (but have no image facility), and many image plugins that make it easy to display previously uploaded images in posts/pages etc., BUT crucially I can't find one that would enable a user to upload an image from the admin profile menus.
Extended requirements for such a function would include:
- the ability to control the size of the uploaded images
- the ability to control the location
- the ability to control the image name
My PHP coding is very basic so I can't code it myself...
During my searches I've seen the following - but these have also led to a dead end:
Any ideas?


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I installed wordpress(2.0.2) on my hosting account at domainspeaks.com . Problem, I am facing is that many people complain of getting error 404 ,wrapped in wordpress, mostly when they submit an application here domainspeaks.com/free-domains/application/2
This problem is not faced by all members and also not everytime, but few members face it constantly and few others face it ocassionally.
I do not have snapshot to show you, as I for myself have not faced it as of now, but its not one or two people, many have reported same to me.
Please help.


text:
Lori H.
Report | 2 years ago
Really great service, honest opinions and much better prices than Michaels. I'll be doing all of my framing from here on out with Frame and Art Gallery.
Was this helpful?
Frame and Art Gallery's staff preserves keepsakes using archival framing materials in addition to conservation-clear, conservation-reflection, and museum-quality glass. Many of their moldings sell for less than $175, efficiently enclosing photographs and other valuable items. Frame and Art Gallery also specializes in framing jerseys, stretching canvases, and art restoration. If shoppers don't already possess artwork they'd like to frame, they can pick up John A. Maxwell original paintings or purchase a pet portrait to memorialize domestic animals without constructing a shrine out of fur.


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I was wondering what happens to my new plugins that I have used to create my child theme when I install the new theme on the live site?
These plugins aren't included in the child theme folder obviously. Do I have to install them again onto the live site?
Will that result in conflict and 'break the site' and make it difficult to get the old theme in place if anything goes wrong?


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Authorities were investigating a possible stabbing at the Casa del Monte Trailer Park on Sunday.
The attack happened on 16th Way South in the trailer park near Forest Hill Boulevard and Jog Road, West Palm Beach Fire Department Capt. Albert Borroto said.
The victim of the attack was taken to Delray Medical Center for treatment.
The views expressed are not those of this site, this station or its affiliated companies. By posting your comments you agree to accept our terms of use.blog comments powered by Disqus


text: Bugs item #729524, was opened at 2003-04-29 14:37 Message generated for change (Tracker Item Submitted) made by Item Submitter You can respond by visiting: https://sourceforge.net/tracker/?func=detail&atid=101355&aid=729524&group_id=1355 Category: None Group: segfault Status: Open Resolution: None Priority: 5 Submitted By: Jörg Höhle (hoehle) Assigned to: Nobody/Anonymous (nobody) Summary: ffi:c-struct corrupt since CVS foreign.d 1.62 Initial Comment: Hi, it looks like the change in CVS saying "do not print system structure definitions do print full prototype for built-in functions" which added options like :external and :typedef to C-STRUCT declarations has some bug. On a CVS-CLISP on Linux, [86]> (ffi::parse-c-type '(c-ptr (c-struct list (a (c-array long 2)) (s (c-array character 3))))) #(C-PTR #(C-STRUCT LIST (A (C-ARRAY LONG 2)) #(S) #<SYSTEM-FUNCTION LIST> #(C-ARRAY CHARACTER 3))) Just by looking at it, that cannot be right! Oddly enough, (ffi::deparse-c-type *) looks fine on this example. In v2.30, the result looked like this #(C-PTR #(C-STRUCT #(A S) #<SYSTEM-FUNCTION LIST> #(C-ARRAY LONG 2) #(C-ARRAY CHARACTER 3))) but the format of #(c-struct ...) now has more fields, so it is not anymore the exact output to expect. Here's one testcase (with-c-var (place '(c-ptr (c-struct list (a (c-array long 2)) (s (c-array character 3)))) '(#(-3 -1) #(#\a #\b #\c))) (slot (deref place) 's)) "abc" Regards, Jörg Höhle. ---------------------------------------------------------------------- You can respond by visiting: https://sourceforge.net/tracker/?func=detail&atid=101355&aid=729524&group_id=1355


text: 06.03.2012 – In a week of celebratory cocktails, Mr. DANIEL RIERA recommends the OLD FASHIONED. "I've been drinking them since I was 16," says DANIEL, "it's my favourite drink and the perfect prelude to a nice night." The OLD FASHIONED combines dissolved sugar, ANGUSTURA BITTERS and bourbon – DANIEL prefers MAKER's MARK – garnished with a slice of orange, for a strong, yet smooth drink. It's a deceptively tricky cocktail, as the dissolving of the sugar takes great patience, and a good one is the mark of a stellar barman. This OLD FASHIONED was enjoyed at the famed BAR COCK, in Madrid. "In the '40s and '50s the COCK was closed off behind another bar and you needed to ring a bell to get in," says DANIEL, "but today it feels like you're at home. I love it."


text: 15 Apr 2014 Titanic: 10 ways to mark the anniversary Previous slide Next slide 1 of 10 View All Skip Ad Spend the night at the Titanic hotel The former Liverpool headquarters of White Star Lines, the firm that owned the Titanic, was recently transformed into a themed hotel . The rebranded 30 James Street - Home of the Titanic - comes complete with 65 "cabins" that sleep up to nine guests, and which capture "the elegant glamour of the 1900s". Many are named after people associated with the disaster, such as Charles Lightoller, the second officer who helped passengers escape, and Wallace Hartley, the English violinist who was the ship's band leader. There's also a Carpathia Bar & Restaurant (named after the ship which rescued 705 survivors). See www.rmstitanichotel.co.uk -- By Oliver Smith Head to Belfast's Titanic visitor attraction Belfast spent £97m - Northern Ireland's biggest-ever outlay on a tourism project - on Titanic Belfast, a glittering edifice at the Harland and Wolff dockyards where the ship was built. It contains no artefacts, but consists of nine galleries telling the tale from rivets to requiem. See titanicbelfast.com This year's Giro d'Italia, the most prestigious multi-day cycling race after the Tour de France, begins in Belfast - in the shadow of the Titanic attraction. Visit the Titanic sites of Southampton Nowhere was the Titanic disaster felt more keenly than in Southampton. The ship set sail from the city, and provided most of the ship's crew. 549 people with Southampton addresses lost their lives - more than a third of the overall death toll. The SeaCity Museum features a permanent exhibition, while in the ruins of Holy Rood Church, on the high street, there is a memorial fountain. The former South Western Hotel, meanwhile, a Grade II-listed building used by first class passengers, has been converted to a bar and restaurant venue called the Grand Café. Other sites associated with the disaster are outlined here . See www.seacitymuseum.co.uk Visit Halifax, Nova Scotia This is where the bodies of victims were taken and buried. The Maritime Museum has a dedicated section that includes a deckchair recovered from the wreck, mortuary bags, and the shoes of an unknown victim. See maritime.museum.gov.ns.ca . Spend the night in New York The Jane hotel in the West Village, built as a hostel for seafarers, was where Titanic survivors were put up during the American inquiry into the disaster and it retains a nautical feel. 113 Jane St, NY, NY 10014 (001 212 924 6700; thejanenyc.com ). Up the coast in Mystic, Connecticut, the town's aquarium features an exhibition Titanic - 12,450ft Below. The work of Dr Robert Ballard, the oceanographer who discovered the wreck of the Titanic, it promises to "transport" visitors to the ship's final resting place. Visit mysticaquarium.org . Credit: ALAMY Visit Cherbourg On the Normandy coast, this was Titanic's first port of call, on the evening of April 10, 1912. According to Greg Ward, our Normandy expert , it is "a bustling port, with a fine array of very fishy restaurants and some well priced hotels. Its chief attraction, the Cité de la Mer, includes an aquarium and a visitable nuclear submarine, and also holds a major exhibition on the Titanic disaster; many of those who died boarded the ill-fated liner here." See www.citedelamer.com Credit: GETtY Visit Cobh Formerly Queenstown, in County Cork, this was Titanic's second port of call, on the morning of April 11, 1912. 123 people stepped from the White Star Line pier onto the waiting tenders here. The Titanic Trail, a walking tour of the town, takes in sites associated with the disaster. See www.titanic.ie Credit: ALAMY Go on a wreck dive The wreck of the Titanic was discovered in 1985 and lies 370 miles off the coast of Newfoundland, around 12,500 feet below the surface. The marine dive specialists Deep Ocean Expeditions previously offered trips to the wreck using a Mir submersible chartered from the Russian Academy of Sciences - with berths costing $59,000 - but stopped offering them in 2012. There are dozens of other fascinating shipwreck dives that cost far less, however, and which you can do without spending 10 hours in cramped container. The RMS Rhone, a Royal Mail steamship that got caught in a hurricane in October 1867, in the British Virgin Islands, is one. See www.divebvi.com/dive-sites/rms-rhone Another is the Bianca C, off the coast of Grand Anse, Grenada. See divegrenada.com/biancac.htm Credit: ALAMY Sail on the Titanic II You'll need to wait a while for this one. Clive Palmer announced his intention to build the Titanic II, a replica of the original, in 2012 , with an inaugural cruise pencilled in for late 2016, sailing the same route from Southampton to New York. However, the project could well be slipping behind schedule. Australian media recently reported that a deal has still not been signed with shipbuilders CSC Jinling, a year after Mr Palmer claimed it was imminent. Credit: GETTY Visit the life-sized replica in China Here's another one for the future. China is notoriously keen on replicas - it even has a theme park called "Window of the World" that features more than 100 reproductions of attractions including the Eiffel Tower and the Taj Mahal - so it was no surprise to hear that a Titanic replica is in the pipeline . It is likely to cost 1 billion yuan (£101 million), is expected to open in 2016, and will be built at least 930 miles from the nearest ocean in the central province of Sichuan. Credit: GETTY Back to image Back to image Back to image Back to image Back to image Back to image Back to image Back to image Back to image Back to image Back to image


text:
I would like to not to mind about type of numbers. All numbers could be treated as Double, but I would like to know the better scalaish way to use numbers just as numbers.
This is just one example, suppose I have the following:
val n = 5
val l = List(1,2,3,4,5) grouped (n / 2d).ceil.toInt
Is there a way to do just (exactly):
val l = List(1,2,3,4,5) grouped (n / 2).ceil
with no compilation error due to the mismatched type of 'grouped' parameter?
n / 2 in
grouped (n / 2).ceil part could be, in another example, the non integer result of a function
grouped f.ceil
It still needs type conversion, or in all situations there is a trick or design pattern to avoid it?


text:
National Cancer Institute
Posted Date: Jan 26, 2016
Expert-reviewed information summary about tests used to detect or screen for breast cancer.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about breast cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Breast Cancer Screening
Note: Separate PDQ summaries on Breast Cancer Prevention, Breast Cancer Treatment, Male Breast Cancer Treatment, and Breast Cancer Treatment and Pregnancy are also available.
This summary covers the topic of breast cancer screening and includes information about breast cancer incidence and mortality, risk factors for breast cancer, the process of breast cancer diagnosis, and the benefits and harms of various breast cancer screening modalities. This summary also includes information about screening among special populations.
Mammography is the most widely used screening modality, with solid evidence of benefit for women aged 40 to 74 years. Clinical breast examination and breast self-exam have also been evaluated but are of uncertain benefit. Technologies such as ultrasound, magnetic resonance imaging, tomosynthesis, and molecular breast imaging are being evaluated, usually as adjuncts to mammography.
Screening With Mammography
Based on solid evidence, screening mammography may lead to the following benefit:
- Decrease in breast cancer mortality Magnitude of Effect: In the randomized controlled trials (RCTs), for women aged 40 to 74 years, screening with mammography has been associated with a 15% to 20% relative reduction in mortality from breast cancer. Absolute mortality benefit for women screened annually for 10 years is approximately 1% overall, ranging from 4 per 10,000 women who start screening at age 40 years to 50 per 10,000 women who start at age 50 years. Based on the 25-year follow-up from the Canadian National Breast Screening Study (CNBSS), an RCT of breast cancer screening, there is some uncertainty about the magnitude of benefit of mammography in the present day.Study Design: RCTs, population-based evidence.Internal Validity: Variable, but meta-analysis of RCTs good.Consistency: Fair.External Validity: Good.
- Magnitude of Effect: In the randomized controlled trials (RCTs), for women aged 40 to 74 years, screening with mammography has been associated with a 15% to 20% relative reduction in mortality from breast cancer. Absolute mortality benefit for women screened annually for 10 years is approximately 1% overall, ranging from 4 per 10,000 women who start screening at age 40 years to 50 per 10,000 women who start at age 50 years. Based on the 25-year follow-up from the Canadian National Breast Screening Study (CNBSS), an RCT of breast cancer screening, there is some uncertainty about the magnitude of benefit of mammography in the present day.
- Study Design: RCTs, population-based evidence.
- Internal Validity: Variable, but meta-analysis of RCTs good.
- Consistency: Fair.
- External Validity: Good.
Based on solid evidence, screening mammography may lead to the following harms:
- Overdiagnosis and Resulting Treatment of Insignificant Cancers: Diagnosis of cancers that would otherwise never have caused symptoms or death in a womanâs lifetime can expose a woman to the immediate risks of therapy (surgical deformity or toxicities from radiation therapy, hormone therapy, or chemotherapy), late sequelae (lymphedema), and late effects of therapeutic radiation (new cancers, scarring, or cardiac toxicity). Although the specific plan of recommended treatment is typically tailored to individual tumor characteristics, at this time, there is no reliable way to distinguish which cancer would never progress in an individual patient; therefore, some treatment is nearly always recommended. Magnitude of Effect: Varies with patient age, life expectancy, and tumor type (ductal carcinoma in situ and/or invasive). Of all breast cancers detected by screening mammograms, up to 54% are estimated to be results of overdiagnosis. The best estimations of overdiagnosis come from either long-term follow-up of RCTs of screening or the calculation of excess incidence in large screening programs. Although there are uncertainties with each approach, follow-up of the long-term CNBSS and well-conducted excess incidence studies in the United States and Scandinavia found that at least 20% of screen-detected breast cancers are overdiagnosed.Study Design: Descriptive population-based comparisons, autopsy series, and series of mammary reduction specimens.
- Magnitude of Effect: Varies with patient age, life expectancy, and tumor type (ductal carcinoma in situ and/or invasive). Of all breast cancers detected by screening mammograms, up to 54% are estimated to be results of overdiagnosis. The best estimations of overdiagnosis come from either long-term follow-up of RCTs of screening or the calculation of excess incidence in large screening programs. Although there are uncertainties with each approach, follow-up of the long-term CNBSS and well-conducted excess incidence studies in the United States and Scandinavia found that at least 20% of screen-detected breast cancers are overdiagnosed.
- Study Design: Descriptive population-based comparisons, autopsy series, and series of mammary reduction specimens.
- False Positives with Additional Testing and Anxiety. Magnitude of Effect: On average, 10% of women will be recalled from each screening examination for further testing, and only 5 of the 100 women recalled will have cancer. Approximately 50% of women screened annually for 10 years in the United States will experience a false positive, of whom 7% to 17% will have biopsies. Additional testing is less likely when prior mammograms are available for comparison.Study Design: Descriptive population-based.
- Magnitude of Effect: On average, 10% of women will be recalled from each screening examination for further testing, and only 5 of the 100 women recalled will have cancer. Approximately 50% of women screened annually for 10 years in the United States will experience a false positive, of whom 7% to 17% will have biopsies. Additional testing is less likely when prior mammograms are available for comparison.
- Study Design: Descriptive population-based.
- False Negatives with False Sense of Security and Potential Delay in Cancer Diagnosis. Magnitude of Effect: 6% to 46% of women with invasive cancer will have negative mammograms, especially if they are young, have dense breasts, or have mucinous, lobular, or rapidly growing cancers.Study design: Descriptive population-based.
- Magnitude of Effect: 6% to 46% of women with invasive cancer will have negative mammograms, especially if they are young, have dense breasts, or have mucinous, lobular, or rapidly growing cancers.
- Study design: Descriptive population-based.
- Radiation-Induced Breast Cancer: Radiation-induced mutations can cause breast cancer, especially if exposure occurs before age 30 years and is at high doses, such as from mantle radiation therapy for Hodgkin disease. The breast dose associated with a typical two-view mammogram is approximately 4 mSv and extremely unlikely to cause cancer. One Sv is equivalent to 200 mammograms. Latency is at least 8 years, and the increased risk is lifelong. Magnitude of Effect: Theoretically, annual mammograms in women aged 40 to 80 years may cause up to one breast cancer per 1,000 women.Study design: Descriptive population-based.
- Magnitude of Effect: Theoretically, annual mammograms in women aged 40 to 80 years may cause up to one breast cancer per 1,000 women.
- Study design: Descriptive population-based.
For all these potential harms of screening mammography, internal validity, consistency and external validity are good.
Clinical Breast Examination
Clinical breast examination (CBE) has not been tested independently; it was used in conjunction with mammography in one Canadian trial, and was the comparator modality versus mammography in another trial. Thus, it is not possible to assess the efficacy of CBE as a screening modality when it is used alone versus usual care (no screening activity).
- Magnitude of Effect: The current evidence is insufficient to assess the additional benefits and harms of CBE. The single RCT comparing high-quality CBE with screening mammography showed equivalent benefit for both modalities. Accuracy in the community setting might be lower than in the RCT.
- Study Design: Single RCT, population cohort studies.
- Internal Validity: Good.
- Consistency and External Validity: Poor.
Screening by CBE may lead to the following harms:
- False Positives with Additional Testing and Anxiety. Magnitude of effect: Specificity in women aged 50 to 59 years was 88% to 99%, yielding a false-positive rate of 1% to 12%.Study Design: Descriptive population-based.Internal Validity, Consistency and External Validity: Good.
- Magnitude of effect: Specificity in women aged 50 to 59 years was 88% to 99%, yielding a false-positive rate of 1% to 12%.
- Study Design: Descriptive population-based.
- Internal Validity, Consistency and External Validity: Good.
- False Negatives with Potential False Reassurance and Delay in Cancer Diagnosis. Magnitude of Effect: Of women with cancer, 17% to 43% have a negative CBE. Sensitivity is higher with longer duration and higher quality of the examination by trained personnel.Study Design: Descriptive population-based.Internal and External Validity: Good.Consistency: Fair.
- Magnitude of Effect: Of women with cancer, 17% to 43% have a negative CBE. Sensitivity is higher with longer duration and higher quality of the examination by trained personnel.
- Study Design: Descriptive population-based.
- Internal and External Validity: Good.
- Consistency: Fair.
Breast Self-Examination
Breast self-examination (BSE) has been compared with usual care (no screening activity) and has not been shown to reduce breast cancer mortality.
- Magnitude of Effect: No effect.
- Study Design: Two RCTs.
- Internal Validity and Consistency: Fair.
- External Validity: Poor.
Based on solid evidence, formal instruction and encouragement to perform BSE leads to more breast biopsies and diagnosis of more benign breast lesions.
- Magnitude of Effects on Health Outcomes: Biopsy rate was 1.8% among the study population compared with 1.0% among the control group.
- Study Design: Two RCTs, cohort studies.
- Internal Validity: Good.
- Consistency: Fair.
- External Validity: Poor.
Description of the Evidence
Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 60,290 cases of in situ disease, 231,840 new cases of invasive disease, and 40,290 deaths expected in 2015. Thus, fewer than 1 of 6 women diagnosed with breast cancer die of the disease. By comparison, about 71,660 American women are estimated to die of lung cancer in 2015. Males account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section of this summary for more information).
Widespread adoption of screening increases breast cancer incidence in a given population and changes the characteristics of cancers detected, with increased incidence of lower-risk cancers, premalignant lesions, and ductal carcinoma in situ (DCIS). (Refer to the Ductal Carcinoma In Situ section in the Breast Cancer Diagnosis and Pathology section of this summary for more information.) Ecologic studies from the United States and the United Kingdom demonstrate an increase in DCIS and invasive breast cancer incidence since the 1970s, attributable to the widespread adoption of both postmenopausal hormone therapy and screening mammography. In the last decade, women have refrained from using postmenopausal hormones, and breast cancer incidence has declined, but not to the levels seen prior to the widespread use of screening mammography.
One might expect that if screening identifies cancers before they cause clinical symptoms, then the period of screening will be followed by a period of compensatory decline in cancer rates, either in annual population incidence rates or in incidence rates in older women. However, no compensatory drop in incidence rates has ever been seen following the adoption of screening, suggesting that screening leads to overdiagnosisâthe identification of clinically insignificant cancers (refer to the Overdiagnosis section in the Harms of Screening section of this summary for more information).
Breast cancer incidence and mortality risk also vary according to geography, culture, race, ethnicity, and socioeconomic status (refer to the Special Populations section of this summary for more information).
Women with breast symptoms are not candidates for screening because they require a diagnostic evaluation. During a 10-year period, 16% of 2,400 women aged 40 to 69 years sought medical attention for breast symptoms at their health maintenance organization. Women younger than 50 years were twice as likely to seek evaluation. Additional testing was performed in 66% of these women, including invasive procedures performed in 27%. Cancer was diagnosed in 6.2% of these women, most often as stage II or stage III. Of the breast symptoms prompting medical attention, a mass was most likely to lead to a cancer diagnosis (10.7%) and pain was least likely (1.8%) to do so.
Risk Factors for Breast Cancer
Breast cancer risk is affected by many factors besides participation in screening activities. Understanding and quantifying these risks is important to a woman, to her physicians, and to public policy makers. (Refer to the PDQ summary on Breast Cancer Prevention for a complete description of factors associated with an increased or decreased risk of breast cancer.)
Pathologic Evaluation of Breast Tissue
Pathologic Diagnosis of Invasive Breast Cancer
Breast cancer is most often diagnosed by pathologic review of a fixed specimen of breast tissue. The breast tissue can be obtained from a symptomatic area or from an area identified by an imaging test. A palpable lesion can be biopsied with core needle biopsy or, less often, fine-needle aspiration biopsy or surgical excision; image guidance improves accuracy. Nonpalpable lesions can be sampled by core needle biopsy using stereotactic x-ray or ultrasound guidance or can be surgically excised after image-guided localization. In a retrospective study of 939 patients with 1,042 mammographically detected lesions who underwent core needle biopsy or surgical needle localization under x-ray guidance, sensitivity for malignancy was greater than 95% and the specificity was greater than 90%. Compared with surgical needle localization under x-ray guidance, core needle biopsy resulted in fewer surgical procedures for definitive treatment, with a higher likelihood of clear surgical margins at the initial excision.
Pathologic Diagnosis of Ductal Carcinoma
Ductal carcinoma in situ (DCIS) is a noninvasive condition that can evolve to invasive cancer, with variable frequency and time course. Some authors include DCIS with invasive breast cancer statistics, but others argue that the term be replaced by ductal intraepithelial neoplasia, similar to the terminology used for cervical and prostate precursor lesions, and that breast cancer statistics exclude these DCIS cases.
DCIS is most often diagnosed by mammography. In the United States, only 4,900 women were diagnosed with DCIS in 1983, compared with approximately 64,000 women who are expected to be diagnosed in 2013, when mammographic screening has been widely adopted. The Canadian National Breast Screening Study-2 of women aged 50 to 59 years found a fourfold increase in DCIS cases in women screened by clinical breast examination (CBE) plus mammography compared with those screened by CBE alone, with no difference in breast cancer mortality. (Refer to the PDQ summary on Breast Cancer Treatment for more information.)
The natural history of DCIS is poorly understood because nearly all DCIS cases are treated. A single retrospective review of 11,760 breast biopsies performed between 1952 and 1968 identified 28 cases of DCIS, which were detected by physical examination, biopsied without resection, and then followed for 30 years. Nine women developed invasive breast cancer and four women died of the disease. These findings are interesting but probably not relevant to women with screen-detected DCIS in an era of improved cancer care.
Development of breast cancer after treatment of DCIS depends on the characteristics of the lesion but also on the delivered treatment. One large randomized trial found that 13.4% of women treated by lumpectomy alone developed ipsilateral invasive breast cancer within 90 months, compared with 3.9% of those treated by lumpectomy and radiation. The best evidence indicates that most DCIS lesions will not evolve to invasive cancer and that those that do can still usually be managed successfully, even after that transition. Thus, the detection and treatment of nonpalpable DCIS often represents overdiagnosis and overtreatment.
Among women diagnosed with (and treated for) DCIS between 1984 and 1989, only 1.9% died of breast cancer within 10 years, which was a lower mortality rate than for the age-matched population at large. This favorable outcome may reflect the benign nature of the condition, the benefits of treatment, or the volunteer effect (women undergoing breast cancer screening are generally healthier than those who do not).
Attempts to define low-risk DCIS cases that can be managed with fewer therapies are important. One such effort analyzed a series of 706 DCIS patients who were monitored to develop the University of Southern California/Van Nuys Prognostic Scoring Index, which defines the risk of recurrent DCIS and invasive cancer among women with DCIS based on age, margin width, tumor size, and grade. The low-risk group, comprising one-third of the cases, experienced only 1% DCIS recurrences and no invasive cancers, independent of the use of postoperative radiation therapy. The moderate- and high-risk groups had higher recurrence rates, and they benefited from postlumpectomy radiation therapy. Overall, only approximately 1% died of breast cancer. In a separate study, adjuvant tamoxifen therapy was shown to reduce the incidence of invasive breast cancer.
Pathologic Diagnosis of Atypia
The prevalence of atypia is low, ranging from 4% to 10% of breast biopsies. However, the large number of breast biopsies performed each year, estimated to be 1.6 million in the United States alone, translates this outcome to a large number of women. Atypia is a diagnostic classification with considerable variation among practicing pathologists. One study of 115 U.S. pathologists reported that study pathologists agreed with an expert consensus diagnosis of atypia only 48% of the time.
Variability of Pathologistsâ?? Diagnoses on the Interpretation of Breast Biopsy Specimens
The pathologistâs diagnosis of breast tissue ranges from benign without atypia to atypia, to DCIS, to invasive breast cancer. The incidence of atypia and DCIS breast lesions has increased over the past three decades as a result of widespread mammography screening. Misclassification of breast lesions may contribute to either overtreatment or undertreatment of lesions identified during breast screening. Studies have demonstrated challenges encountered by pathologists on agreeing about the diagnoses of breast tissue, especially atypia and DCIS. The largest study on this topic included 115 practicing U.S. pathologists who interpreted a single breast biopsy slide per case and compared their interpretations with an expert consensus-derived reference diagnosis. Although overinterpretation of DCIS as invasive carcinoma occurred in only 3% (95% confidence interval [CI], 2%â4%), overinterpretation of atypia was noted in 17% (95% CI, 15%â21%), and overinterpretation of benign without atypia was noted in 13% (95% CI, 11%â15%). While underinterpretation of invasive breast cancer was noted in 4% (95% CI, 3%â6%) in this study, many of these underinterpretations were caused by an invasive test case that contained predominantly DCIS with a focus of microinvasion. Underinterpretation of DCIS was noted in 13% (95% CI, 12%â15%), and underinterpretation of atypia was noted in 35% (95% CI, 31%â39%).
To address the high rates of discordance in breast tissue diagnosis, laboratory policies that require second opinions are becoming more common. A recent national survey of 252 breast pathologists found that 65% of respondents reported having a laboratory policy that require second opinions for all cases initially diagnosed as invasive disease. Additionally, 56% of respondents reported policies that require second opinions for initial diagnosis of DCIS, while 36% of respondents reported mandatory second opinion policies for cases initially diagnosed as atypical ductal hyperplasia. In this same survey, pathologists overwhelmingly agreed that second opinions improved diagnostic accuracy (96%).
Breast Cancer Screening Concepts
Numerous uncontrolled trials and retrospective series have documented the ability of mammography to diagnose small, early-stage breast cancers, which have a favorable clinical course. Although several trials also show better cancer-related survival in screened versus nonscreened women, a number of important biases may explain that finding:
Because the extent of these biases is never clear in any particular study, most groups rely on randomized controlled trials to assess the benefits of screening. (Refer to the PDQ summary on Cancer Screening Overview for more information.)
Assessment of Performance and Accuracy
Performance benchmarks for screening mammography in the United States are described on the Breast Cancer Surveillance Consortium (BCSC) website.
The sensitivity of mammography is the percentage of breast cancers detected in a given population, when breast cancer is present. Sensitivity depends on tumor size, conspicuity, and hormone sensitivity as well as breast tissue density, patient age, timing within the menstrual cycle, overall image quality, and interpretive skill of the radiologist. Overall sensitivity is approximately 79% but is lower in younger women and in those with dense breast tissue (see the BCSC website). Delay in diagnosis of breast cancer is the most common cause of medical malpractice litigation and one-half of the cases resulting in payment to the claimant involve false-negative mammograms.
The specificity of mammography is the likelihood of the test being normal when cancer is absent, whereas the false-positive rate is the likelihood of the test being abnormal when cancer is absent. If specificity is low, many false-positive examinations result in unnecessary follow-up examinations and procedures. (Refer to the subsection on Harms in the Screening With Mammography section of the Overview section of this summary for more information.)
Interval cancers are cancers that are diagnosed in the interval after a normal screening examination and before the subsequent screen. Some of these cancers were present at the time of mammography (false negatives), and others grew rapidly in the interval between mammography and detection. As a general rule, interval cancers have characteristics of rapid growth and are frequently of advanced stage at the time of discovery/diagnosis.
One study of 576 women with interval cancers reported that interval cancers are more prevalent in women aged 40 to 49 years. Interval cancers appearing within 12 months of a negative screening mammogram appear to be related to decreased mammographic sensitivity, attributable to greater breast density in 68% of cases. Those appearing within a 24-month interval appear to be related both to decreased mammographic sensitivity caused by greater breast density in 37.6% of cases and to rapid tumor growth in 30.6% of cases.
Another study that compared the characteristics of 279 screen-detected cancers with those of 150 interval cancers found that interval cancers were much more likely to occur in women younger than 50 years and to be of mucinous or lobular histology; or to have high histologic grade, high proliferative activity, relatively benign features mammographically and/or to lack calcifications. Screen-detected cancers were more likely to have tubular histology; to be smaller, low stage, and hormone sensitive; and to have a major component of ductal carcinoma in situ.
Breast Cancer Screening Imaging Modalities
Mammography Description and Background
Mammography utilizes ionizing radiation to image breast tissue. The examination is performed by compressing the breast firmly between two plates. Such compression spreads out overlapping tissues and reduces the amount of radiation needed to image the breast. For routine screening in the United States, examinations are taken in both mediolateral oblique and craniocaudal projections. Both views should include breast tissue from the nipple to the pectoral muscle. Radiation exposure is 4 to 24 mSv per standard two-view screening examination. Two-view examinations are associated with a lower recall rate than are single-view examinations because they eliminate concern about abnormalities due to superimposition of normal breast structures. Two-view exams are also associated with lower interval cancer rates than are single-view exams.
Under the Mammography Quality Standards Act (MQSA) enacted by Congress in 1992, all U.S. facilities that perform mammography must be certified by the U.S. Food and Drug Administration (FDA) to ensure the use of standardized training for personnel and a standardized mammography technique utilizing a low radiation dose. (Refer to the FDA's web page on Mammography Facility Surveys, Mammography Equipment Evaluations, and Medical Physicist Qualification Requirement under MQSA.) The 1998 MQSA Reauthorization Act requires that patients receive a written lay-language summary of mammography results.
The following Breast Imaging Reporting and Data System (BI-RADS) categories are used for reporting mammographic results:
- 0: Incompleteâneeds additional image evaluation and/or prior mammograms for comparison.
- 1: Negative.
- 2: Benign.
- 3: Probably benign.
- 4: Suspicious.
- 5: Highly suggestive of malignancy.
- 6: Known biopsyâproven malignancy.
Most screening mammograms are typically interpreted as negative or benign (BI-RADS 1 or 2, respectively), with about 10% of women in the United States being asked to return for additional evaluation. The percentage of women asked to return for additional evaluation varies not only by the underlying characteristics of each woman but also by mammography facility and radiologist. Extensive literature shows increasing rates of malignancy with BI-RADS assessment categories, with less than 1% risk for diagnosis of cancer within the next year after a BI-RADS 1 or 2 assessment, 2% risk for diagnosis of cancer within the next year after a BI-RADS 3 assessment, and 95% risk for diagnosis of cancer within the next year after a BI-RADS 5 assessment. A BI-RADS 4 can optionally be subdivided into categories 4a, low suspicion (>2% to 10% risk of malignancy); 4b, moderate suspicion (>10% to 50% risk of malignancy); and 4c, high suspicion (>50% to <95% risk of malignancy).
Digital Mammography
Digital mammography is more expensive than screen-film mammography (SFM) but is more amenable to data storage and sharing. The net impact of screening with digital mammography versus film mammography, in terms of health outcomes and the net difference in rates of overdiagnosis, is unknown. Performance of both SFM and digital mammography for measures such as cancer detection rate, sensitivity, specificity, and positive predictive value (PPV) have been compared directly in several trials, and the trials yielded similar results.
A large cohort of women (n = 42,760) who underwent both digital and film mammography was evaluated at 33 U.S. centers in the Digital Mammographic Imaging Screening Trial (DMIST). No differences in breast cancer detection were observed (area under the curve [AUC] of 0.78 +/- 0.02 for digital and AUC of 0.74 +/- 0.02 for film; P = .18). Digital mammography was better at cancer detection in women younger than 50 years (AUC of 0.84 +/- 0.03 for digital; AUC of 0.69 +/- 0.05 for film; P = .002).
A second DMIST report found that film mammography had a higher AUC in women aged 65 years and older (AUC 0.88 for film; AUC 0.70 for digital; P = .025); however, this finding was not statistically significant when multiple comparisons were considered.
In a large U.S. cohort study, sensitivity for women younger than 50 years was 75.7% (95% CI, 71.7â79.3) for film mammography and 82.4% (95% CI, 76.3â87.5) for digital mammography; specificity was 89.7% (95% CI, 89.6â89.8) for film mammography and 88.0% (95% CI, 88.2â87.8) for digital mammography. A comparison of the findings from 1.5 million digital mammography screens and 4.5 million screen-film mammogram (SFM) screens that were performed in the Netherlands from 2004 to 2010 indicated higher recall and detection rates for the digital mammography screens. Among radiologists who read both digital and SFM exams (n = 1.5 million), the recall rates were 2.0% for digital mammography (95% CI, 2.0â2.1) versus 1.6% for SFM (95% CI, 1.6â1.6); the detection rates were 5.9 per 1,000 (95% CI, 5.7â6.0) for digital mammography and 5.1 per 1,000 (95% CI, 5.0â5.2) for SFM. The PPV was statistically significantly lower in the digital mammography group (PPV, 31.2%; 95% CI, 30.6â31.7) than in the screen-film group (PPV, 34.4%; 95% CI, 33.8%â35.0%). For women aged 49 to 54 years, the recall rates for digital screens versus film screens were 2.7% versus 2.0%, respectively; the detection rates were 5.1 versus 4.0 per 1,000 screens, respectively; and the PPV was 21.4% and 22.1%, respectively. For women aged 55 to 74 years, the recall rates for digital screens versus film screens were 1.7% versus 1.4%, respectively; the detection rates were 6.2 versus 5.6 per 1,000 screens, respectively; and the PPV was 35.7% versus 40.1%, respectively.
A meta-analysis of 10 studies, including the DMIST and the aforementioned U.S. cohort study, compared digital mammography with film mammography in 82,573 women who underwent both types of the exam. In a random-effects model, there was no statistically significant difference in cancer detection between the two types of mammography (AUC of 0.92 for film and AUC of 0.91 for digital). For women younger than 50 years, all studies found that sensitivity was higher for digital mammography but that specificity was either the same or higher for film mammography. The meta-analysis found no other differences based on age.
Computed radiography (CR) utilizes a cassette-based removable detector and external reading device to generate a digital image. A large concurrent cohort study compared 254,758 full-field digital mammography (FFDM) screens with 487,334 SFM screens and 74,190 CR screens. Again, the cancer detection rate was not different between FFDM (4.9 per 1,000) and SFM (4.8 per 1,000), although the recall rate was higher for FFDM. Importantly, cancer detection was lower for CR at 3.4 per 1,000, adjusted odds ratio (OR) 0.79 (95% CI, 0.68â0.93). Two prior studies of noncontemporaneous cohorts showed no difference between CR and SFM or higher cancer-detection rate from CR.
Computer-Aided Detection (CAD)
CAD systems are designed to help radiologists read mammograms by highlighting suspicious regions such as clustered microcalcifications and masses. Generally, CAD systems increase sensitivity and decrease specificity and increase detection of ductal carcinoma in situ (DCIS). Several CAD systems are in use. One large population-based study, comparing recall rates and breast cancer detection rates before and after the introduction of CAD systems found no change in either rate. Another large study noted an increase in recall rate and increased DCIS detection but no improvement in invasive cancer detection rate.
Population-Based Evaluation of Digital Mammography and CAD
Using a Surveillance, Epidemiology, and End ResultsâMedicare linked database, the use of new screening mammography modalities by more than 270,000 women aged 65 years and older in two time periods, 2001 to 2002 and 2008 to 2009, was examined. Digital mammography increased from 2% to 30%, CAD increased from 3% to 33%, and spending increased from $660 million to $962 million. There was no difference in detection rates of early-stage (DCIS or stage I) or late-stage (stage IV) tumors.
Tomosynthesis, or 3-dimensional (3-D) mammography, is similar to standard 2-D mammography in how the examination is performed: the breasts are compressed in the same positions as for mammography, and the examination uses x-rays to create the image. In tomosynthesis, multiple short-exposure x-rays are obtained at different angles as the x-ray tube moves over the breast. This process takes a few seconds longer than a standard mammogram. Individual images are then reconstructed into a series of thin slices that can be viewed individually or like a movie. Cancers and other abnormalities are detected because of differences in density and shape compared with surrounding tissue, with some cancers and other findings causing architectural distortion. Overlapping tissues can be more easily recognized accurately as normal with tomosynthesis, and some cancers are better seen than on standard mammography. In some centers, tomosynthesis-guided biopsy may be available because some cancers seen only on tomosynthesis cannot be found with ultrasound.
The combination of 2-D and 3-D mammography has been reported to be more accurate than 2-D mammography alone, with respect to both improved detection of breast cancer (averaging added yield of 1.3/1,000, similar to CAD) and, importantly, reduction in recall rates. On average, 1.8% fewer women will be recalled for extra testing when tomosynthesis is performed in addition to standard 2-D digital mammography for screening. More than 80% of the cancers detected only with tomosynthesis are invasive and node negative. In particular, tomosynthesis depicts architectural distortion better than standard digital mammography; in one series of 26 cases of architectural distortion in women who had both 2-D and 3-D mammography, 19 (73%) were seen only on tomosynthesis, and 4 (21%) of those 19 were malignant.
When tomosynthesis is performed in combination with 2-D mammography, the resulting radiation exposure to the patient is essentially doubled. This is expected to result in another 1.3 fatal cancers per 100,000 women screened at age 40 years (fewer with increasing age), compared with another 130 cancers detected (see Table 1).
The performance of tomosynthesis in isolation (with synthetic 2-D mammograms created) has not been adequately validated in practice, with only one reader study and one prospective clinical trial undertaken to date. The effect of annual tomosynthesis on breast cancer mortality has not been tested in a prospective clinical trial.
Tomosynthesis in the diagnostic setting (specifically, evaluation of mammographic abnormalities) has been shown to be at least as effective as spot compression views for workup of noncalcified abnormalities, including asymmetries and distortions. Tomosynthesis is not worse than standard 2-D mammography at allowing suspicious microcalcifications to be identified, but magnification views are typically still needed to characterize suspicious calcifications.
The use of tomosynthesis in both screening and diagnosis may decrease the need for ultrasound and other additional testing (see Table 1). At this time, there are no data on the association of tomosynthesis and overall mortality reduction.
The primary role of ultrasound is the diagnostic evaluation of palpable or mammographically identified masses, rather than serving as a primary screening modality. A review of the literature and expert opinion by the European Group for Breast Cancer Screening concluded that âthere is little evidence to support the use of ultrasound in population breast cancer screening at any age.â In the setting of normal mammography and ultrasonography, less than 3% of women who have a lump will ultimately be found to have breast cancer.
Magnetic Resonance Imaging
Breast magnetic resonance imaging (MRI) may be used in women for diagnostic evaluation, including evaluating the integrity of silicone breast implants, assessing palpable masses following surgery or radiation therapy, detecting mammographically and sonographically occult breast cancer in patients with axillary nodal metastasis, and preoperative planning for some patients with known breast cancer. There is no ionizing radiation exposure with this procedure. It has been promoted as a screening test for breast cancer among women at elevated risk of breast cancer based on BRCA1/2 mutation carriers, a strong family history of breast cancer, or several genetic syndromes such as Li-Fraumeni or Cowden disease. Breast MRI is more sensitive but less specific than screening mammography and is more expensive.
Using infrared imaging techniques, thermography of the breast identifies temperature changes in the skin as an indicator of an underlying tumor, displaying these changes in color patterns. Thermographic devices have been approved by the FDA under the 510(k) process, which does not require evidence of clinical effectiveness. There have been no randomized trials of thermography to evaluate the impact on breast cancer mortality or the ability to detect breast cancer. Small cohort studies do not suggest any additional benefit for the use of thermography as an adjunct modality for breast cancer screening.
Benefit of Screening
Randomized controlled trials (RCTs), with participation by nearly half-a-million women from four countries, examined the breast cancer mortality rates of women who were offered regular screening. One trial, the Canadian National Breast Screening Study (NBSS)-2, compared mammogram plus clinical breast examination (CBE) with CBE alone; the other eight trials compared screening mammogram with or without CBE to a control consisting of usual care.
The trials differed in design, recruitment of participants, interventions (both screening and treatment), management of the control group, compliance with assignment to screening and control groups, and analysis of outcomes. Some trials used individual randomization, while others used cluster randomization in which cohorts were identified and then offered screening; one trial used nonrandomized allocation by day of birth in any given month. Cluster randomization sometimes led to imbalances between the intervention and control groups. Age differences have been identified in several trials, although the differences were probably too small to have a major effect on the trial outcome. In the Edinburgh Trial, socioeconomic status, which correlates with the risk of breast cancer mortality, differed markedly between the intervention and control groups, so it is difficult, if not impossible, to interpret the results.
Breast cancer mortality is the major outcome parameter for each of these trials, so the methods used to determine cause of death are critically important. Efforts to reduce bias in the attribution of mortality cause have been made, including the use of a blinded monitoring committee (New York) and a linkage to independent data sources, such as national mortality registries (Swedish trials). Unfortunately, these attempts could not ensure a lack of knowledge of womenâs assignments to screening or control arms. Evidence of possible misclassification of breast cancer deaths in the Two-County Trial with possible bias in favor of screening has been analyzed.
There were also differences in the methodology used to analyze the results of these trials. Four of the five Swedish trials were designed to include a single screening mammogram in the control group, timed to correspond with the end of the series of screening mammograms in the study group. The initial analysis of these trials used an "evaluation" analysis, tallying only the breast cancer deaths that occurred in women whose cancer was discovered at or before the last study mammogram. In some of the trials a delay occurred in the performance of the end-of-study mammogram, resulting in more time for members of the control group to develop or be diagnosed with breast cancer. Other trials used a "follow-up" analysis, which counts all deaths attributed to breast cancer, regardless of the time of diagnosis. This type of analysis was used in a meta-analysis of four of the five Swedish trials in response to concerns about the evaluation analyses.
The accessibility of the data for international audits and verification also varies, with formal audit having been undertaken only in the Canadian trials. Other trials have been audited to varying degrees, usually with less rigor.
All of these studies are designed to study breast cancer mortality rather than all-cause mortality because of the infrequency of breast cancer deaths relative to the total number of deaths. When all-cause mortality in these trials was examined retrospectively, only the Edinburgh Trial showed a significant difference, which could be attributed to socioeconomic differences. The meta-analysis (follow-up methods) of the four Swedish trials also showed a small but significant improvement of all-cause mortality.
Refer to the Appendix of Randomized Controlled Trials section of this summary for a detailed description of the trials.
Screening for breast cancer does not affect overall mortality, and the absolute benefit for breast cancer mortality is small.
A way to view the potential benefit of breast cancer screening is to estimate the number of lives extended because of early breast cancer detection. One author estimated the outcomes of 10,000 women aged 50 to 70 years who undergo a single screen. Mammograms will be normal (true negatives and false negatives) in 9,500 women. Of the 500 abnormal screens, 466 to 479 will be false-positives, and 100 to 200 of these women will undergo invasive procedures. The remaining 21 to 34 abnormal screens will be true positives, indicating breast cancer. Some of these women will die of breast cancer in spite of mammographic detection and optimal therapy, and some may live long enough to die of other causes even if the cancer had not been screen detected. The number of extended lives attributable to mammographic detection is between two and six. Another expression of this analysis is that one life may be extended per 1,700 to 5,000 women screened and followed for 15 years. The same analysis for 10,000 women aged 40 to 49 years, assuming the same 500 abnormal examinations, results in an estimate that 488 of these will be false positives, and 12 will be breast cancer. Of these 12, there will probably be only one or two lives extended. Thus, for women aged 40 to 49 years, it is estimated that one or two lives may be extended per 5,000 to 10,000 mammograms.
While the numbers discussed above are from a single mammography exam, women undergo screening throughout their lifetimes, which can include 20 to 30 years of screening activity. A meta-analysis of RCTs conducted for the U.S. Preventive Services Task Force in 2009 (including the AGE Trial) found that the number needed to invite to screen for 10 years to avoid or delay one death from breast cancer was 1,904 for women in their 40s, 1,339 for women in their 50s, and 377 for women in their 60s. A 2009 combined analysis by six Cancer Intervention and Surveillance Modeling Network modeling groups found that screening every 2 years maintained an average of 81% of the benefit of annual screening with almost one-half of the false-positive results. Screening biennially from age 50 to 69 years achieved a median 16.5% reduction in breast cancer deaths versus no screening. Initiating biennial screening at age 40 years (vs. age 50 years) reduced breast cancer mortality by an additional 3%, consumed more resources, and yielded more false-positive results.
There are several problems with using these RCTs alone to estimate the magnitude of breast cancer mortality reduction from a long-term program of breast cancer screening in the present. These problems include the following:
Although there is no ideal answer to these problems, it is a good idea to take into account well-conducted cohort and ecologic studies, in addition to RCTs, in the estimation of the magnitude of breast cancer mortality reduction resulting from current day screening.
Effectiveness of Population-Based Screening Programs
Although the RCTs of screening have addressed the issue of screening efficacy (i.e., the extent to which screening reduces breast cancer mortality under the ideal conditions of an RCT), they do not provide information about the effectiveness of screening (i.e., the extent to which screening is reducing breast cancer mortality in the U.S. population). Studies that provide information about this issue include nonrandomized controlled studies of screened versus nonscreened populations, case-control studies of screening in real communities, and modeling studies that examine the impact of screening on large populations. An important issue in all of these studies is the extent to which they can control for additional effects on breast cancer mortality such as improved treatment and heightened awareness of breast cancer in the community.
Three population-based, observational studies from Sweden compared breast cancer mortality in the presence and absence of screening mammography programs. One study compared two adjacent time periods in 7 of the 25 counties in Sweden and concluded a statistically significant breast cancer mortality reduction of 18% to 32% attributable to screening. The most important bias in this study is that the advent of screening in these counties occurred over a period during which dramatic improvements in the effectiveness of adjuvant breast cancer therapy were being made, changes which were not addressed by the study authors. The second study considered an 11-year period comparing seven counties with screening programs with five counties without them. There was a trend in favor of screening, but again, the authors did not consider the effect of adjuvant therapy or differences in geography (urban vs. rural) that might affect treatment practices.
In part to account for the effects of treatment, the third study was a detailed analysis by county and concluded little impact of screening. These authors made the assumption that the annual decrease in mortality observed during the prescreening period would carry into the postscreening period, and any screening effect would result in an incremental decrease in mortality. Although no such incremental decrease in breast cancer mortality was observed after the introduction of screening, their assumption makes their conclusion weak. Comparisons across counties showed similar reductions in decreased breast cancer mortality regardless of when the countiesâ screening programs were initiated; however, the authors carried out no formal cross-county analyses.
The interpretation of this ecologic analysis is limited by the following factors:
- The analysis did not isolate incident breast cancer cases diagnosed before the introduction of breast cancer screening from the analysis of breast cancer deaths after the introduction of screening. These cases account for more than one-half of all deaths in a 10-year period after the introduction of screening.
- The analysis did not adjust for trends in increasing incidence (which put upward pressure on mortality rates, independent of screening).
- Unlike the observational studies, the third study did not measure exposure to screening.
- The analysis did not compensate for deaths avoided after age 70 years resulting from breast cancer detection by mammography before age 70 years.
- The analysis did not adjust for opportunistic screening that occurred in some counties.
- The analysis did not account for the duration of time that is required to implement screening in the counties, which varied (i.e., screening is not fully effective the day after screening becomes policy and counties varied in the pace of screening implementation).
In Nijmegen, the Netherlands, where a population-based screening program was undertaken in 1975, a case-cohort study showed that screened women have decreased mortality (OR, 0.48). However, a subsequent study comparing Nijmegen breast cancer mortality rates with neighboring Arnhem in the Netherlands, which had no screening program, showed no difference in breast cancer mortality.
A community-based case-control study of screening as practiced in excellent U.S. health care systems between 1983 and 1998 found no association between previous screening and reduced breast cancer mortality. Mammography screening rates, however, were generally low. The association among women at increased risk because of a family history of breast cancer or a previous breast biopsy (OR, 0.74; 95% CI, 0.50â1.03) was stronger than that among women at average risk (OR, 0.96; 95% CI, 0.80â1.14), but the difference was not statistically significant (P = .17).
A well-conducted ecologic study compared three pairs of neighboring European countries, matched on similarity in health care systems and population structure, one of which had started a national screening program some years earlier than the others. The investigators found that each country had experienced a reduction in breast cancer mortality, with no difference between matched pairs that could be attributed to screening. The authors suggested that improvements in breast cancer treatment and/or health care organizations were more likely responsible for the reduction in mortality than was screening.
A systematic review of ecologic and large cohort studies published through March 2011 compared breast cancer mortality in large populations of women aged 50 to 69 years who started breast cancer screening at different times. Seventeen studies met inclusion criteria. All studies had methodological problems, including control group dissimilarities, insufficient adjustment for differences between areas in breast cancer risk and breast cancer treatment, and problems with similar measurement of breast cancer mortality between compared areas. There was great variation in results among the studies, with four studies finding a relative reduction in breast cancer mortality of 33% or more (with wide CIs) and five studies finding no reduction in breast cancer mortality. Because only a part of the overall reduction in breast cancer mortality could possibly be attributed to screening, the review concluded that any relative reduction in breast cancer mortality resulting from screening would likely be no more than 10%, less than predicted by the RCTs.
A U.S. ecologic analysis conducted between 1976 and 2008 examined the incidence of early-stage versus late-stage breast cancer for women aged 40 years and older. To find a screening effect, the authors compared the magnitude of increase in early-stage cancer with the magnitude of an expected decrease in late-stage cancer. Over the study period, the absolute increase in the incidence of early-stage cancer was 122 cancers per 100,000 women, while the absolute decrease in late-stage cancers was 8 cases per 100,000 women. After adjusting for changes in incidence resulting from hormone therapy and other undefined causes, the authors concluded that the screening effect on breast cancer mortality reduction (28% during this period) was small, and that overdiagnosis of breast cancer was likely between 22% and 31% of all diagnosed breast cancers. Most of the reduction in breast cancer mortality, the authors concluded, was probably because of improved treatment rather than screening. To make these adjustments, the authors made uncertain assumptions about the effects of other factors on incidence, and made no mention of the effects of changing treatment over time. Ecologic studies are difficult to interpret because of this type of potential uncontrolled confounding, as well as these types of unfair comparisons. However, this study largely agrees with some similar analyses from other countries (see studies discussed above). A major limitation of this and other ecologic studies is the failure to account for actual exposure to screening. Most late-stage breast cancer occurs in women not exposed to screening.
A prospective cohort study of community-based screening programs in the United States found that annual compared with biennial screening mammography did not reduce the proportion of unfavorable breast cancers detected in women aged 50 to 74 years or in women aged 40 to 49 years who did not have extremely dense breasts. Women aged 40 to 49 years with extremely dense breasts did have a reduction in cancers larger than 2.0 cm (OR for biennial vs. annual screening, 2.39; 95% CI, 1.37â4.18).
Statistical Modeling of Breast Cancer Incidence and Mortality in the United States
The optimal screening interval has been addressed by modelers. Modeling makes assumptions that may not be correct; however, the credibility of modeling is greater when the model produces overall results that are consistent with randomized trials overall and when the model is used to interpolate or extrapolate. For example, if a modelâs output agrees with RCT outcomes for annual screening, it has greater credibility in comparing the relative effectiveness of biennial versus annual screening.
In 2000, the National Cancer Institute formed a consortium of modeling groups (Cancer Intervention and Surveillance Modeling [CISNET]) to address the relative contribution of screening and adjuvant therapy to the observed decline in breast cancer mortality in the United States. (Refer to the Randomized controlled trials section of this summary for more information.) These models gave reductions in breast cancer mortality similar to those expected in the circumstances of the RCTs but updated to the use of modern adjuvant therapy. In 2009, CISNET modelers addressed several questions related to the harms and benefits of mammography, including comparing annual versus biennial screening. The proportion of reduction in breast cancer mortality maintained in moving from annual to biennial screening for women aged 50 to 74 years ranged across the six models from 72% to 95%, with a median of 80%.
Characteristics of Cancers Detected by Breast Imaging
Several studies have shown that the method of cancer detection is a powerful predictor of patient outcome, which is useful for prognostication and treatment decisions. All of the studies accounted for stage, nodal status, and tumor size.
A 10-year follow-up study of 1,983 Finnish women with invasive breast cancer demonstrated that the method of cancer detection is an independent prognostic variable. When controlled for age, nodal status, and tumor size, screen-detected cancers had a lower risk of relapse and better overall survival. For women whose cancers were detected outside screening, the hazard ratio (HR) for death was 1.90 (95% confidence interval [CI], 1.15â3.11), even though they were more likely to receive adjuvant systemic therapy.
Similarly, an examination of the breast cancers found in three randomized screening trials (Health Insurance Plan, National Breast Screening Study [NBSS]-1, and NBSS-2) accounted for stage, nodal status, and tumor size and determined that patients whose cancer was found via screening have a more favorable prognosis. The relative risks for death were 1.53 (95% CI, 1.17â2.00) for interval and incident cancers, compared with screen-detected cancers; and 1.36 (95% CI, 1.10â1.68) for cancers in the control group, compared with screen-detected cancers.
A third study compared the outcomes of 5,604 English women with screen-detected cancers to those with symptomatic breast cancers diagnosed between 1998 and 2003. After controlling for tumor size, nodal status, grade, and patient age, researchers found that the women with screen-detected cancers fared better than their symptomatic counterparts. The HR for survival of the symptomatic women was 0.79 (95% CI, 0.63â0.99). Thus, method of cancer detection is a powerful predictor of patient outcome, which is useful for prognostication and treatment decisions. The findings of this study are also consistent with the evidence that some screen-detected cancers are low risk and represent overdiagnosis.
Variables Associated with Accuracy
Patient Characteristics
Several characteristics of women being screened that are associated with the accuracy of mammography include age, breast density, whether it is the first or subsequent exam, and time since last mammogram. Younger women have lower sensitivity and higher false-positive rates on screening mammography than do older women (refer to the Breast Cancer Surveillance Consortium performance measures by age for more information).
For women of all ages, high breast density is associated with 10% to 29% lower sensitivity. High breast density is an inherent trait, which can be familial but also may be affected by age, endogenous and exogenous hormones, selective estrogen receptor modulators such as tamoxifen, and diet. Hormone therapy is associated with increased breast density and is associated not only with lower sensitivity but also with an increased rate of interval cancers.
The Million Women Study in the United Kingdom revealed three patient characteristics that were associated with decreased sensitivity and specificity of screening mammograms in women aged 50 to 64 years: use of postmenopausal hormone therapy, prior breast surgery, and body mass index below 25. In addition, a longer interval since the last mammogram increases sensitivity, recall rate, and cancer detection rate and decreases specificity.
Strategies have been proposed to improve mammographic sensitivity by altering diet, timing mammograms with menstrual cycles, interrupting hormone therapy before the examination, or using digital mammography machines. Obese women have more than a 20% increased risk of having false-positive mammography results compared with underweight and normal weight women, although sensitivity is unchanged.
Tumor Characteristics
Some cancers are more easily detected by mammography than other cancers are. In particular, mucinous, lobular, and rapidly growing can
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