FDA Update on Rare Breast Implant-Associated Type of Lymphoma


The US Food and Drug Administration (FDA) has provided an update on breast implant–associated anaplastic large cell lymphoma.

In January 2011, the agency identified a possible associationbetween breast implants and the development of anaplastic large cell lymphoma (ALCL).

 Since then, “we have strengthened our understanding of this condition and concur with the World Health Organization designation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as a rare T-cell lymphoma that can develop following breast implants,” the FDA said in a statement March 21.

Over 350 Cases, 9 Deaths

The FDA notes that most data suggest that BIA-ALCL occurs more often after implantation of breast implants with textured surfaces rather than those with smooth surfaces.

As of February 1, 2017, the FDA has received a total of 359 medical device reports (MDRs) of BIA-ALCL, including 9 deaths. Of the 231 reports that included information on the implant surface, 203 concerned textured implants and 28, smooth implants.

Of the 312 reports that included information on implant fill types, 186 described implants filled with silicone gel and 126, implants filled with saline.

“It is important to note that details on breast implant surface and fill type are limited. While the MDR system is a valuable source of information, it may contain incomplete, inaccurate, untimely, unverified, or biased data,” the FDA says.

 During the last 6 years, a “significant body” of literature has been published on BIA-ALCL, including additional case histories and comprehensive reviews of the natural history and long-term outcomes of the disease, the agency notes.  “All of the information to date suggests that women with breast implants have a very low but increased risk of developing ALCL compared to women who do not have breast implants.”

Most cases of BIA-ALCL are treated by removal of the implant and the capsule surrounding the implant, and some cases have been treated by chemotherapy and radiation. However, because BIA-ALCL has “generally only been identified in patients with late onset of symptoms such as pain, lumps, swelling, or asymmetry, prophylactic breast implant removal in patients without symptoms or other abnormality is not recommended,” the FDA said.

The exact number of cases of BIA-ALCL worldwide is unknown.

The FDA is continuing to collect and evaluate information about BIA-ALCL. For now, the agency recommends that clinicians who have patients with breast implants take the following action:

  • Be aware that most confirmed cases of BIA-ALCL have occurred in women with textured breast implants. Provide the manufacturer’s labeling as well as any other educational materials to your patients before surgery and discuss with them the benefits and risks of the different types of implants.
  • Consider the possibility of BIA-ALCL in a patient with late-onset, persistent peri-implant seroma. In some cases, patients presented with capsular contracture or masses adjacent to the breast implant. A patient with suspected BIA-ALCL should be referred to an appropriate specialist for evaluation. When testing for BIA-ALCL, collect fresh seroma fluid and representative portions of the capsule and send for pathology tests to rule out BIA-ALCL. Diagnostic evaluation should include cytologic evaluation of seroma fluid with Wright-Giemsa–stained smears and cell block immunohistochemistry testing for cluster of differentiation and anaplastic lymphoma kinase markers.
  • Develop an individualized treatment plan in coordination with the patient’s multidisciplinary care team. Consider current clinical practice guidelines, such as those from the Plastic Surgery Foundation  or the National Comprehensive Cancer Network (NCCN) when choosing your treatment approach.
  • Report all confirmed cases of ALCL in women with breast implants to the FDA’s MedWatch system.

Source:medscape.com

German firm liable over PIP implants.


A French court has ordered a German company to pay compensation to hundreds of women who were fitted with defective breast implants.

TUV Rheinland, which awarded EU safety certificates to the French implant manufacturer, “neglected its duties of vigilance”, the court said.

Virginia Moon, lawyer of Argentine women in the lawsuit for defective Poly Implant Prothese (PIP) French-made breast implants, shows one of them in her office at the district courts during a press conference

PIP (Poly Implant Prothese) was shut down in March 2010 amidst a worldwide health scare.

The company used sub-standard silicone gel, causing many implants to rupture.

PIP implants scandal in numbers

  • More than 300,000 women affected in 65 countries
  • 4,000 reported ruptures
  • PIP exported 80% of its implants, with half going to Latin America
  • 42,000 British, 25,000 Brazilian, 15,000 Colombian, 30,000 French, 16,000 Venezuelan women received PIP implants
  • 15,000 French women have had their PIP implants removed under instruction from the government
  • 5,000 women registered as plaintiffs in the PIP trial
  • 1,700 women registered in the TUV Rheinland trial

Six implant distributors and 1,700 women had sued TUV Rheinland for 50m euros (£42m), arguing anything but a cursory inspection would have found problems.

The plaintiffs in the civil case will be given an initial payment of 3,000 euros per victim for surgery to have the implants removed.

Jan Spivey, a British woman who received PIP implants as part of reconstructive surgery following breast cancer in 2002, said she was “delighted” with the ruling.

“Of course TUV has some responsibility and should be held to account. They’re the organisation that gives the CE certification for safety, and that was what my surgeon relied on when he gave the implants to me.

“Anybody that gives safety certification for a product that is going to make women very sick does have responsibility,” she told the BBC’s Newshour programme.

It could open the door to many more compensation claims, says the BBC’s Christian Fraser in Paris.

TUV Rheinland had won two previous cases in Germany. This was the first such case in France.

The German firm has said it will appeal against the verdict.

Hidden from view

TUV Rheinland awarded PIP – formerly one of the world’s leading suppliers of implants – its European safety certificate for 17 years.

Carol Robson, who was one of the 1,700 plaintiffs. said she was “happy” with the compensation ruling

The founder of PIP, Jean Claude Mas, is still on trial for aggravated fraud in Marseilles, along with four of his executives.

He revealed during police interviews that he had ordered employees to hide the unauthorised silicone when inspectors visited his factory.

It has since emerged the substandard gel was used in 75% of the implants.

The court heard an employee in charge of quality control had only a cooking diploma – another in charge of the lab had previously trained as a pastry chef, our correspondent says.

A ruling is expected in Jean Claude Mas’ case on 10 December.

Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update.


Abstract

Purpose To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent.

Methods To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating.

Results There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted.

Recommendations Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose–positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

Source: JCO

Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies.


Abstract

Objectives To evaluate whether the stage distribution among women diagnosed as having breast cancer differs between those who have received breast implants for cosmetic purposes and those with no implants and to evaluate whether cosmetic breast augmentation before the detection of breast cancer is a predictor of post-diagnosis survival.

Design Systematic review of observational studies with two meta-analyses.

Data sources Systematic search of the literature published before September 2012 conducted in Medline, Embase, Global health, CINAHL, IPAB, and PsycINFO.

Study selection Eligible publications were those that included women diagnosed as having breast cancer and who had had augmentation mammaplasty for cosmetic purposes.

Results The overall odds ratio of the first meta-analysis based on 12 studies was 1.26 (95% confidence interval 0.99 to 1.60; P=0.058; I2=35.6%) for a non-localized stage of breast cancer at diagnosis comparing women with implants who had breast cancer and women without implants who had breast cancer. The second meta-analysis, based on five studies, evaluated the relation between cosmetic breast implantation and survival. This meta-analysis showed reduced survival after breast cancer among women who had implants compared with those who did not (overall hazard ratio for breast cancer specific mortality 1.38, 95% confidence interval 1.08 to 1.75).

Conclusions The research published to date suggests that cosmetic breast augmentation adversely affects the survival of women who are subsequently diagnosed as having breast cancer. These findings should be interpreted with caution, as some studies included in the meta-analysis on survival did not adjust for potential confounders. Further investigations are warranted regarding diagnosis and prognosis of breast cancer among women with breast implants.

Discussion

This systematic review suggests that women with cosmetic breast implants have later stage tumors at diagnosis of breast cancer. In our second meta-analysis, the results show a higher risk of breast cancer specific mortality among women with breast cancer who have implants compared with women with breast cancer without implants. Nevertheless, the overall estimate should still be interpreted with caution because this meta-analysis included a relatively small number of studies. Of concern, three of five studies had unadjusted hazard ratios (not adjusted for age at diagnosis, or period of diagnosis) and all five studies were unadjusted for other potential confounding factors such as body mass index, which could translate into a biased estimate of the summary hazard ratio. A lack of adjustment for body mass index has previously been shown to lead to underestimation of the association between cosmetic breast implants and breast cancer mortality.18 Moreover, one study included in this meta-analysis assessed overall mortality rather than breast cancer specific mortality,39 which could have biased our summary estimate towards the null. The small number of studies and insufficient amount of follow-up time in these studies are suspected to limit statistical power to clearly evaluate survival rate patterns among augmented women. Given the limited evidence, no conclusion regarding breast cancer specific survival can be drawn and continued follow-up to further evaluate this question is particularly relevant.

Source: BMJ

Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies


 

Objectives To evaluate whether the stage distribution among women diagnosed as having breast cancer differs between those who have received breast implants for cosmetic purposes and those with no implants and to evaluate whether cosmetic breast augmentation before the detection of breast cancer is a predictor of post-diagnosis survival.

Design Systematic review of observational studies with two meta-analyses.

Data sources Systematic search of the literature published before September 2012 conducted in Medline, Embase, Global health, CINAHL, IPAB, and PsycINFO.

Study selection Eligible publications were those that included women diagnosed as having breast cancer and who had had augmentation mammaplasty for cosmetic purposes.

Results The overall odds ratio of the first meta-analysis based on 12 studies was 1.26 (95% confidence interval 0.99 to 1.60; P=0.058; I2=35.6%) for a non-localized stage of breast cancer at diagnosis comparing women with implants who had breast cancer and women without implants who had breast cancer. The second meta-analysis, based on five studies, evaluated the relation between cosmetic breast implantation and survival. This meta-analysis showed reduced survival after breast cancer among women who had implants compared with those who did not (overall hazard ratio for breast cancer specific mortality 1.38, 95% confidence interval 1.08 to 1.75).

Conclusions The research published to date suggests that cosmetic breast augmentation adversely affects the survival of women who are subsequently diagnosed as having breast cancer. These findings should be interpreted with caution, as some studies included in the meta-analysis on survival did not adjust for potential confounders. Further investigations are warranted regarding diagnosis and prognosis of breast cancer among women with breast implants.

Discussion

This systematic review suggests that women with cosmetic breast implants have later stage tumors at diagnosis of breast cancer. In our second meta-analysis, the results show a higher risk of breast cancer specific mortality among women with breast cancer who have implants compared with women with breast cancer without implants. Nevertheless, the overall estimate should still be interpreted with caution because this meta-analysis included a relatively small number of studies. Of concern, three of five studies had unadjusted hazard ratios (not adjusted for age at diagnosis, or period of diagnosis) and all five studies were unadjusted for other potential confounding factors such as body mass index, which could translate into a biased estimate of the summary hazard ratio. A lack of adjustment for body mass index has previously been shown to lead to underestimation of the association between cosmetic breast implants and breast cancer mortality.18 Moreover, one study included in this meta-analysis assessed overall mortality rather than breast cancer specific mortality,39 which could have biased our summary estimate towards the null. The small number of studies and insufficient amount of follow-up time in these studies are suspected to limit statistical power to clearly evaluate survival rate patterns among augmented women. Given the limited evidence, no conclusion regarding breast cancer specific survival can be drawn and continued follow-up to further evaluate this question is particularly relevant.

Source: BMJ