A rare form of leukaemia linked to breast implants occurs far more often than previously reported, according to a review of national cancer databases.
From 2008 until 2018, primary breast anaplastic large-cell lymphoma (ALCL) occurred at a rate of 8.1 per 100m people per year, translating into a cumulative lifetime risk of 7.5/100m at age 79. The rate increased over time, reaching 14.5/100m for 2012 to 2018. That compared with a US Food & Drug Administration (FDA) estimate of 3/100m for 2001 to 2007.
The higher rate of breast ALCL in the US is consistent with reports from the Netherlands, Australia and New Zealand.
The rising case rate also coincided with increasing use of textured breast implants, which have been implicated in breast ALCL, reported Dr Connor Kinslow of the Columbia University Vagelos College of Physicians and Surgeons in New York City, and co-authors in JAMA Oncology.
“Previous studies have underestimated the risk of this rare cancer after breast implantation,” Kinslow told MedPage Today. “The hope is that these data will contextualise previous studies (to improve) understanding that (the number of cases) have been underestimated and that they will continue to underestimate the rate of ALCL.
“Risk estimates have varied widely in previous studies and, accordingly, different governments have had very different responses,” he added. “In Australia they banned certain types of textured implants. In the US, they put a black box label on all implants. Some countries haven’t taken any action. Getting more accurate risk estimates will help governments decide how they should be responding to this.”
Though “certainly concerning”, the findings came from a study period that ended in 2018, the year before the FDA and regulatory agencies in other countries issued a recall of Allergan textured implants, the ones most closely associated with ALCL, noted Dr Deanna Attai of the David Geffen School of Medicine at the University of Los Angeles.
“As all national databases lag by several years, it may be too soon to determine if the incidence of ALCL has decreased as a result of the recall,” Attai, who was not involved in the analysis, told MedPage Today. “However, as the FDA has not recommended removal of textured implants in the absence of symptoms, women with textured implants should be aware that prior estimates of the risk of ALCL are lower than what is currently being reported.”
Historical perspective
More than a decade ago, the FDA issued an initial safety communication about silicone gel-filled implants. In the year before the Allergan recall, the FDA noted a growing number of cases of implant-associated ALCL and released updated numbers several months before asking Allergan to withdraw its textured breast implants from the market.
Other makers of textured implants were not affected by the recall. The agency subsequently called for a boxed warning for all implants sold in America.
Neither the recall nor the boxed warning recommended removal of breast implants in the absence of signs and symptoms. Population-based estimates of the incidence of breast ALCL in the US have been lacking, Kinslow and co-authors noted. Authors of one frequently cited study of ALCL estimated that 3m women in the US had textured breast implants as of 2015.
MedicalBrief reported in 2019 that more than 200 women were considering legal action over the controversial Allergan breast implants. According to an Onmedica report at the time, the implants were withdrawn from the European market in December after it was revealed that six of the women who received the implants developed ALCL.
Figures collected by plastic surgeons suggested that globally there had been at least 615 cases of the disease associated with breast implants and 16 deaths. In the UK, where textured implants have been generally favoured by surgeons, there had, up till then, been 45 confirmed cases of the lymphoma, and one fatality. The health regulator estimated the risk at one in 24,000 women with implants.
It is not known how many women in this country have these Allergan implants, but the first case report documentation of a South African woman diagnosed with BIA-ALCL was published in Oncological Medicine on 31 May this year.
Study 1 details
Incidence of Anaplastic Large-Cell Lymphoma of the Breast in the US, 2000 to 2018
Connor J. Kinslow, Arreum Kim, 4Gloria I. Sanchez, et al.
Published in JAMA Network on 21 July 2022
Anaplastic large-cell lymphoma (ALCL) of the breast is a rare malignant condition, representing approximately 3% of breast lymphomas, and has been identified as a possible adverse effect of breast implants. In 2020, the Food and Drug Administration (FDA) mandated a black box warning on the labelling of all saline- and silicone gel–filled implants warning of an association with ALCL. The incidence of breast ALCL has increased in Australia and New Zealand and the Netherlands, which is thought to be secondary to an increased use of textured implants. However, to our knowledge, there are no current population-based estimates of the incidence of breast ALCL in the US.
Methods
In this cohort study, we determined crude and age-adjusted incidence rates of pathologically confirmed primary breast ALCL diagnosed in females from January 1, 2000, through December 31, 2018, using the Surveillance, Epidemiology, and End Results (SEER) 18 database. We also conducted a sensitivity analysis, including cases of mature T-cell lymphoma not otherwise specified. Cumulative risk was calculated using the crude annual incidence rates in 5-year age categories. We calculated trends in age-adjusted incidence using a linear regression model with Pearson correlation. For external validation, we compared coverage of ALCL in SEER and the National Program of Cancer Registries with FDA-reported cases (eMethods in the Supplement). Statistical analyses were conducted using SEER*Stat, version 8.3.9 (National Cancer Institute), and RStudio, version 1.4.1106 (RStudio Inc), software. The study was exempt from review by the Columbia University Institutional Review Board based on institutional policy regarding non–human participant research.
Results
From 2000 to 2018, the age-adjusted incidence rate of primary breast ALCL in females was 8.1 (95% CI, 6.3-10.2) per 100 million persons per year (unless otherwise stated, results are given per 100 million persons per year), with a cumulative lifetime risk of 7.5 per million persons at age 79 years (Figure 1). The age-adjusted annual incidence rate increased over time, from 3.2 (95% CI, 1.4-6.3) in 2000 to 2005 and 4.4 (95% CI, 2.2-7.7) in 2006 to 2011 to 14.5 (95% CI, 10.8-19.3) in 2012 to 2018 (P < .001) (Figure 2). Similar rates and trends were observed when including cases of T-cell lymphoma not otherwise specified, with a rate of 19.6 (95% CI, 15.1-24.9) in 2012 to 2018. We estimated 353 and 310 cases of breast ALCL diagnosed through 2017 using SEER and SEER/National Program of Cancer Registries data, respectively, compared with 333 cases reported to the FDA over a similar period.
Study 2 details
A South African Breast Implant-Associated Anaplastic Large Cell Lymphoma: Clinical Presentation and Six-Year Follow-Up
Alexandra Grubnik, Yastira Ramdas, Barend Van der Bergh, Simon Nayler, Carol-Ann Benn, and Bernardo L. Rapoport
Published in Oncological Medicine on 31 May 2022
Abstract
Breast augmentation is the most common surgical procedure for women globally, with 1,795,551 cases performed in 2019. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is highly uncommon, with 733 reported cases as of January 2020. In South Africa, there are less than 4000 breast augmentation surgeries annually.
This case presents the first case report documentation of a South African woman diagnosed with BIA-ALCL. The patient was a 61-year-old woman who consulted the Breast Care Centre of Excellence in Johannesburg in 2015. She had a prior history of bilateral augmentation mammoplasty with subsequent implant exchange. The patient presented with periprosthetic fluid with a mass-like enhancement on the left breast. Aspiration of the mass-like fluid was positive for CD45, CD30, and CD68 and negative for CD20 and ALK-1, indicative of BIA-ALCL. Surgical treatment included bilateral explantation, complete capsulectomies, and bilateral mastopexy. Macroscopic examination of the left breast capsulectomy demonstrated fibrous connective tissue.
The histological examination of the tumor showed extensive areas of broad coagulative necrosis with foamy histiocytes. Immunohistochemistry examination of this tumor showed CD3-, CD20-, and ALK-1-negative and CD30- and CD68-positive stains. PCR analysis for T-cell clonality showed monoclonal T-cell expansion. These findings confirm the presence of BIA-ALCL. The patient recovered well after surgery and did not require adjuvant therapy. A patient with a confirmed diagnosis of BIA-ALCL was successfully treated with explantation and complete capsulectomy. She was followed up regularly for six years, and the patient remains well and in remission.
MedPage Today article – Breast Implant-Related Leukemia More Common Than Reported (Open access)
See more from MedicalBrief archives:
UK won’t join France and Australia in banning breast implants linked to cancer
Women ponder litigation over Allergan breast implants link to rare cancer
Some breast implants associated with rare cancer deaths
FDA sets stronger safety warnings for breast implants