More on Implant-Related ALCL of the Breast – an Article Review

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. 

Last week @prsjournal tweeted

Pre-print Article: Patient Death Attributable to Implant-Related Primary Anaplastic Large Cell Lymphoma of the B... http://bit.ly/o9lQ1f

The title definitely caught my eye.  I have finally read it and re-read it.
Here’s the abstract:

Implant-related primary anaplastic large cell lymphoma (ALCL) of the breast is a rare clinical entity. With increasing attention being paid to this disease, most cases reported to date in the literature have demonstrated indolent clinical courses responsive to explantation, capsulectomy, chemotherapy and/or radiotherapy.

We describe a case of bilateral implant-related primary ALCL of the breast that proved refractory to both standard and aggressive interventions, ultimately resulting in patient death secondary to disease progression. We situate this case in the context of the current state of knowledge regarding implant-related primary ALCL of the breast and suggest that this entity is generally, but not universally, indolent in nature.

The story of implant-related ALCL is far from being completely written.  This article notes (as did the recent FDA report) most investigations performed to date suggest an association between breast implants and primary ALCL of the breast.  The specifics regarding this relationship remain poorly defined.

A review of all reported cases of implant-related primary ALCL of the breast demonstrates no obvious correlation with implant fill type (silicone vs. saline), surface morphology (smooth vs. textured), implant position (subpectoral vs. subglandular), or indication for implant placement (cosmetic vs. reconstructive).

The FDA notes (bold emphasis is mine):

ALCL is a very rare condition; when it occurs, it has been most often identified in patients undergoing implant revision operations for late onset, persistent seroma. Because it is so rare and most often identified in patients with late onset of symptoms such as pain, lumps, swelling, or asymmetry, it is unlikely that increased screening of asymptomatic patients would change their clinical outcomes. The FDA does not recommend prophylactic breast implant removal in patients without symptoms or other abnormality.

……..

The FDA is requesting health care professionals report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program. Report online or by calling 800-332-1088.

Related posts:

More on Link Between Breast Implants and ALCL (April 25, 2011)

ALCL and Breast Implants – an article review (March 9, 2011)
ALCL and Breast Implants (January 31, 2011)
Breast Implants and Lymphoma Risk (June 29, 2009)


REFERENCE

Patient Death Attributable to Implant-Related Primary Anaplastic Large Cell Lymphoma of the Breast: A Case Report and Review of the Literature; Carty, Matthew J.; Pribaz, Julian J.; Antin, Joseph H.; Volpicelli, Elgida R.; Toomey, Christiana E.; Farkash, Evan A.; Hochberg, Ephraim P.; Plastic & Reconstructive Surgery., POST ACCEPTANCE, 19 July 2011; doi: 10.1097/PRS.0b013e318221db96

More on Link Between Breast Implants and ALCL

Updated 3/2017-- photos and all links (except to my own posts) removed as many no longer active. 

I have written about this previously. 
ALCL and Breast Implants – an article review (March 9, 2011)
ALCL and Breast Implants (January 31, 2011)
Breast Implants and Lymphoma Risk (June 29, 2009)

A quick review:  In January, the Food and Drug Administration (FDA) released a safety alert warning of the possible association of acute large cell lymphoma (ALCL) with breast implants.

After the Plastic Surgery Societies got through being defensive (http://www.theplasticsurgerychannel.com/fda-issues-safety-signal-on-alcl-breast-implants/), they did the right thing  reviewed the literature (4th reference below) and the Plastic Surgery Foundation and the Aesthetic Surgery Education and Research Foundation commissioned RAND to conduct an exhaustive review of the medical literature and organize a panel of medical experts to evaluate the evidence for a potential link and its implications.

The results of this RAND review confirmed breast implants do indeed appear to be associated with the rare form of lymphoma ALCL.  The report notes there is not yet evidence to show that the cancer is caused by implants or to suggest an underlying mechanism for how the disease might develop.

The study, published online (3rd reference below) by the journal Plastic and Reconstructive Surgery, also finds that the disease takes a slow course and can be controlled by surgical removal of the implant and surrounding capsule.

The conclusions are based on an exhaustive review of the medical literature regarding breast implants and anaplastic large cell lymphoma or ALCL, a type of immune system cancer that was first linked to breast implants more than a decade ago, and input from a multidisciplinary expert panel.

"Much more research is still needed to explore the link between breast implants and ALCL and the clinical significance of this rare disease, but our findings provide useful information for both patients and physicians in the near term," said Dr. Soeren Mattke, the study's senior author and a senior scientist at RAND, a nonprofit research organization.

The panel concluded that the evidence suggests an association between breast implants and anaplastic large cell lymphoma, but cannot definitely prove that implants cause the disease nor explain how the implants might trigger ALCL.

The experts recommended that the appearance of a fluid-filled sac near a breast implant six or more months after surgery should lead to a thorough diagnostic evaluation for anaplastic large cell lymphoma. They also concluded that the diagnosis of anaplastic large cell lymphoma should result in a complete evaluation to rule out spread of the disease outside of the breast capsule (the lining that forms around the implant), followed by removal of the implant and capsule.

Experts did not believe that disease confined to the implant capsule warrants radiation treatment or chemotherapy after surgery and expressed the belief that the risk of recurrence or development of systemic disease following surgical removal was low, but that close clinical follow-up was necessary.

The U.S. Food and Drug Administration and the American Society of Plastic Surgeons recently announced an effort to create a registry that will collect information on women with breast implants who have been diagnosed with anaplastic large cell lymphoma in order to gather information that will help increase understanding of the disease.

Health care professionals are requested to report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program. Report online at http://www.fda.gov/Safety/MedWatch/default.htm or
by calling 800-332-1088.


REFERENCES
1.  RAND Corporation;  Press Release April 19, 2011
2.  FDA safety alert; January 2011

3.  Anaplastic Large Cell Lymphoma and Breast Implants: Results From a Structured Expert Consultation Process; Kim, Benjamin; Roth, Carol; Young, V. Leroy; Chung, Kevin C.; van Busum, Kristin; Schnyer, Christopher; Mattke, Soeren; Plastic & Reconstructive Surgery., POST ACCEPTANCE, 15 April 2011; doi: 10.1097/PRS.0b013e31821f9f23

4.  Anaplastic Large Cell Lymphoma and Breast Implants: A Systematic Review; Kim, Benjamin; Roth, Carol; Chung, Kevin C.; Young, V. Leroy; van Busum, Kristin; Schnyer, Christopher; Mattke, Soeren; Plastic & Reconstr Surgery., POST ACCEPTANCE, 25 February 2011; doi: 10.1097/PRS.0b013e3182172418

ALCL and Breast Implants – an article review

 Updated 3/2017--  all links removed as many are no longer active and it was easier than checking each one.

In light of the recent new regarding the FDA safety alert on the possible association of acute large cell lymphoma (ALCL) with breast implants, the authors of the recently Plastic and Reconstructive Surgery Journal article (full reference below, published online ahead of print) conducted a systematic literature search on the topic.

The search included the literature of PubMed, Embase, and Web of Science (Science Journals & Proceedings) databases.  Dates searched included references from 1966 for PubMed and Embase ; from 1980 for Web of Science; and from 1990 for Web of Science Proceedings, through July 2010 for all of them.

Research (categorized as epidemiologic studies or scientific papers) and non-research (case reports or case series) articles from peer-reviewed journals, conference abstracts, and unpublished manuscripts were retrieved from the literature search.

Only human-based topics and articles written in English were considered. Of the initial 884 titles, 83 articles discussed ALCL and breast implants. Fourteen additional articles were provided by 2 expert plastic surgeons (V.L.Y. and K.C.C.).

Their conclusions:

A form of ALCL, which clinically behaves more like the less-aggressive cutaneous form of ALK-negative ALCL rather than the more-aggressive systemic form, may be associated with breast implants. Future research on the epidemiology and biology of this rare disease is clearly needed to better understand its nature.

What is conclusive:

• ALCL is a rare disease, comprising 2% of all newly-diagnosed non-Hodgkin’s lymphomas (NHLs) worldwide2 and 0.9% of the estimated 65,540 cases of NHL diagnosed in the U.S. in 2010.
• Lymphomas of the breast are extremely rare, comprising 0.04-
  0.5% of all breast cancers and approximately 1-2% of all extranodal lymphomas.
• Despite the rarity of both ALCL and primary breast lymphomas, multiple cases of ALCL developing adjacent to breast implants have been reported, including by Brody et al., who have recently presented but not yet published a series of 34 cases.
• In 2009 alone, a reported 289,328 breast augmentation, 86,424 reconstruction, and 87,386 lift procedures were performed in the U.S.; unfortunately, the exact number of women who received implants is not known because only some breast reconstructions and lift procedures utilized implants.

The literature review noted the case presentation characteristics (bold emphasis is mine):

Fourteen (48%) of 29 ALCL cases were noted to have presented with a seroma, 1 (3%) ALCL case did not present as a seroma and data was not reported in the remaining 14 (48%) ALCL cases.

Seven (24%) of the 29 ALCL cases reported data indicating that the patient had a palpable breast mass on presentation, 5 (17%) reported absence of a mass and information was missing for the remaining 17 (59%) ALCL cases.

Less frequently cited symptoms among ALCL cases were pain [6/29 (21%], redness [4/29 (14%)], and capsule contracture [2/29
(7%)].

Other symptoms (e.g., skin lesions, fever) were reported in only 2 (7%) of 29 ALCL cases but in 5 (71%) of 7 patients with other NHLs [not reported in 27/29 (93%) ALCL and 2/7 (29%) non-
ALCL cases].

Duration of symptoms was rarely noted. In the 7 cases where it was, mean duration in years for ALCL cases was 0.8 (range 0.2-1.7). Mean symptom duration among 5 non-ALCL cases for which it was reported was 5.4 years (range 0.5-17).

…..
Remember the FDA report noted (bold emphasis is mine):

ALCL is a very rare condition; when it occurs, it has been most often identified in patients undergoing implant revision operations for late onset, persistent seroma. Because it is so rare and most often identified in patients with late onset of symptoms such as pain, lumps, swelling, or asymmetry, it is unlikely that increased screening of asymptomatic patients would change their clinical outcomes. The FDA does not recommend prophylactic breast implant removal in patients without symptoms or other abnormality.

…..
Of interest is this post from Maggie Mahr:  The FDA “Has a Chat” With Plastic Surgeons

………….It is probably not a coincidence that ASPSS and ASAPS repeated the cancer-denial line first promulgated by Allergan: Both organizations have received funding from the company. ASPSS has also received funding from Allergan’s main competitor, J&J, which makes the Mentor implant line. (Mentor’s reaction to the FDA warning was more muted than Allergan’s but its statement also avoided mentioning the C-word.)

Both Allergan and J&J fund provide funds for ASPSS, as noted on its web site.

At ASAPS, Allergan’s funding is more indirect. It has supplied research grants through ASAPS’ research arm, the Aesthetic Surgery Education and Research Foundation. You can see those grant award announcements by searching for “Allergan” here.

The two groups ought to be ashamed of themselves. It is one thing to take funding from drug and device companies . .  . . But the groups ought to represent the medical expertise of the healthcare providers who are their members, not the PR agendas of two companies who are afraid they may lose money from too much blunt but accurate talk about breast cancer.

Previous related posts:
ALCL and Breast Implants (January 31, 2011)
Breast Implants and Lymphoma Risk (June 29, 2009)


REFERENCE

Anaplastic Large Cell Lymphoma and Breast Implants: A Systematic Review; Kim, Benjamin; Roth, Carol; Chung, Kevin C.; Young, V. Leroy; van Busum, Kristin; Schnyer, Christopher; Mattke, Soeren; Plastic & Reconstr Surgery., POST ACCEPTANCE, 25 February 2011; doi: 10.1097/PRS.0b013e3182172418