Connor J. Kinslow, MD
David P. Horowitz, MD
Alfred I. Neugut, MD, PhD, MPH
The U.S. Food and Drug Administration (FDA) issued a safety communication,1 which was updated2 on March 22, 2023, informing the public that there have been reports of squamous cell carcinomas (SCC) and various lymphomas of the breast in the capsule or scar of breast implants. These lymphomas are unique from breast implant–associated anaplastic large cell lymphoma (ALCL), which was the subject of a “black box” warning3 on all saline and silicone implants since 2020. What does this mean for women with or who want breast implants? First, let’s briefly review the history of implant-related malignancies.
A Brief History
Concerns that breast implants were causing cancers and rheumatologic disorders date back to the 1980s, when silicone implants became more popular. With insufficient evidence to demonstrate the safety of implants, the FDA issued a moratorium on silicone-filled implants in 1992 to be available only for reconstructive surgery or through controlled clinical studies. An association between silicone implants and increased risks of various cancers, including lymphomas, was subsequently disproved through several epidemiologic studies. These studies did not specifically look at the risk of breast implant–associated ALCL, which was not a known entity at that time. The moratorium was lifted in 2006. There was no such moratorium placed in Europe, and so Europeans continued to use silicone implants.
In 1998, the first report in the medical literature was published of ALCL in the capsule of a breast implant, which was subsequently cured by removal of the implant. It should be appreciated how rare these tumors are, making up less than 3% of breast lymphomas, which are already quite rare. Similar cases were subsequently reported, and pathologists found the genetics of breast implant–associated ALCLs were different from that of ALCLs in other parts of the body (often ALK-negative), suggesting a distinct etiology.
In 2008, a seminal paper was published in JAMA,4 which provided the first epidemiologic evidence of an association between breast implants and ALCL. This Dutch population-based study found the risk of breast ALCL in women with implants was elevated by approximately 40 times, although the occurrence was still very rare.
The FDA subsequently issued a safety communication in 2011 of an association between breast implants and ALCL. The association was confirmed in epidemiologic studies in the United States5 and Australia/New Zealand.6 Breast implant–associated ALCLs almost always occurred in association with macrotextured implants—implants with a textured surface that helps them adhere to native tissue. Many cases occurred in association with a specific model of implants manufactured by Allergan/Biocell.
“The jury may still be out on the risk of SCC. However, the association of ALCL with macrotextured implants is well established.”— CONNOR J. KINSLOW, MD, AND COLLEAGUES
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In 2019, the FDA requested that Allergan make a voluntary recall of the product, which was obliged by the company worldwide. In 2020, the FDA issued a “black box” warning on all saline and silicone implants, warning of an association with ALCL. Responses from other governmental regulatory agencies around the world have varied. Australia, France, and Canada have suspended or banned either specific brands of macrotextured implants or all macrotextured implants. Other countries in Europe and throughout the world have not implemented any specific bans or regulations.
Most recently, in 2023, the FDA announced additional SCCs and “various lymphomas” associated with the capsule of breast implants. This announcement was based on 19 cases in the medical literature of implant-associated SCCs. In comparison, there have been approximately 1,400 cases of implant-associated ALCL reported worldwide.
What Is the Risk of Implant-Associated SCC?
Our group was motivated to measure the association between implants and breast SCC,7 given the paucity of cases reported and the lack of empiric evidence. We retrospectively identified a cohort of approximately 57,000 women who underwent mastectomy with implant-based reconstruction for breast cancer or pre-cancer treatment and “followed” the cohort for subsequent breast SCC. Most women were followed for around 6 to 7 years. Two cases of SCC of the breast were identified. Although the risk of SCC was approximately twice as high as expected, the risk was not statistically significant; so, we cannot say with any reasonable confidence that the increased risk was more than pure chance. The bottom line is the risk of breast SCC is extremely low.
Of course, our study has the following caveats:
1. Most women were followed for 6 to 7 years. In contrast, most cases of breast SCC are diagnosed about 20 years after implantation. It is likely we may find more cases of breast SCC if the women were followed for longer. Still, approximately 16,000 women were followed for more than 10 years without any additional cases.
2. All women underwent reconstructive surgery after mastectomy. It is unknown whether our results would be applicable to women who undergo cosmetic implantation.
3. We had no information on implant type. However, unlike breast ALCL, which occurs almost exclusively in women with macrotextured implants, SCC has been reported in association with both smooth and textured implants.
What About the Risk of ALCL?
The jury may still be out on the risk of SCC. However, the association of ALCL with macrotextured implants is well established. In larger epidemiologic studies, the risk has been reported between the range of 1 in 30,000 women and 1 in 3,000 women. In one smaller institutional study, the risk was as high as 1 in 600 women. In our opinion, the best study was conducted by the Dutch group; it found the risk to be approximately 1 in 12,000 women, but it depends on the type of implant and the duration of follow-up. A study from Australia/New Zealand found the risk associated with textured implants to be approximately 1 in 3,000 to 1 in 86,000, depending on the manufacturer. There appears to be no risk associated with smooth implants.
It is also not known whether the risk is different between reconstructive and cosmetic implantation. Some researchers have suggested the risk may be higher in women who undergo reconstruction. However, we have studied this7 and found the risk is still extremely low and, in our opinion, probably similar. Additionally, our group and others have found the number of cases of ALCL diagnosed per year in the United States8 and around the world is rapidly rising. Thus, the risk of ALCL may have been underestimated in previous studies, and we may find in the future that the risk is higher than we previously thought.
Why Are Textured Implants Used?
The textured surface is favored by some surgeons because it may maintain the position of the implant better. The textured surface may be thought of as a better “grip” on the native tissue.
In Europe and in Australia/New Zealand, textured implants make up more than 90% of the market. In contrast, in the United States, textured implants account for less than 20% of the market. The reason is historical; when the FDA ordered a moratorium on silicone implants in 1992, this included textured implants, which are made of silicone. As a result, U.S. plastic surgeons trained with smooth implants and probably became more comfortable using them. Recently, the popularity of textured implants is increasing in the United States, even after the FDA’s 2011 warning. One study showed the use of textured implants increased from 5% to 15% from 2012 to 2018.9
What Are the Clinical Implications for Women Who Want Implants?
Implant-associated SCC is an aggressive disease and sometimes fatal. Fortunately, these cases are extremely rare, and currently, it’s unclear whether the risk is significantly elevated in women with implants. ALCL, on the other hand, can usually be cured by removing the implant. Very few deaths have been reported, and this has occurred in cases when the lymphoma has spread outside the breast capsule into the lymph nodes or distant sites of the body.
For women who undergo mastectomy for breast cancer treatment or prevention, reconstruction can be important for quality of life. The risk of ALCL in women who undergo reconstruction is extremely low. We previously found the risk of ALCL in women who undergo reconstruction (most followed for about 7 years) is approximately 1 in 10,000 women.10 In comparison, the risk of breast cancer recurrence or a new breast cancer can be between 5% and 15%.
“Women who are interested in cosmetic implantation but are worried about the risk of ALCL should discuss smooth implants with their surgeon.”— CONNOR J. KINSLOW, MD, AND COLLEAGUES
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For women who are interested in cosmetic implantation, the decision may be more individualized. Since the procedure is purely cosmetic, many women may be unwilling to tolerate any risk of malignancy, no matter how small. Furthermore, few studies have reported outcomes after 20 years. For a woman receiving implants in her 20s, 30s, or 40s, not knowing the long-term risks several decades out may dissuade them. Women who are interested in cosmetic implantation but are worried about the risk of ALCL should discuss smooth implants with their surgeon. The risk of ALCL with smooth implants is probably close to zero.
What About Women Who Already Have Breast Implants?
For women with implants, there is no recommendation from the United States or any other country, to our knowledge, that the implant should be removed prophylactically. Instead, women should continue routine follow-up with their surgeon or another physician. They should report any new symptoms to their doctor, including changes lumps, swelling, pain, redness, or skin changes in the breast.
DISCLOSURE: Dr. Kinslow and Dr. Horowitz reported no conflicts of interest. Dr. Neugut has consulted for Otsuka, Organon, GlaxoSmithKline, United Biosource Corp, Value Analytics, Merck, and EHE International.
REFERENCES
1. Rabin RC: Breast implants may be linked to additional cancers, FDA warns. The New York Times. September 8, 2022. Available at www.nytimes.com/2022/09/08/health/breast-implants-cancer.html. Accessed March 21, 2024.
2. U.S. Food and Drug Administration: UPDATE: Reports of squamous cell carcinoma in the capsule around breast implants—FDA Safety Communication. March 22, 2023. Available at www.fda.gov/medical-devices/safety-communications/update-reports-squamous-cell-carcinoma-scc-capsule-around-breast-implants-fda-safety-communication. Accessed March 21, 2024.
3. Rabin RC: Patients must be warned of breast implant risks, FDA warns. The New York Times. October 27, 2021. Available at www.nytimes.com/2021/10/27/health/breast-implants-cancer-fda.html. Accessed March 21, 2024.
4. de Jong D, Vasmel WLE, de Boer JP, et al: Anaplastic large-cell lymphoma in women with breast implants. JAMA 300:2030-2035, 2008.
5. Doren EL, Miranda RN, Selber JC, et al: U.S. epidemiology of breast implant-associated anaplastic large cell lymphoma. Plast Reconstr Surg 139:1042-1050, 2017.
6. Loch-Wilkinson A, Beath KJ, Knight RJW, et al: Breast implant-associated anaplastic large cell lymphoma in Australia and New Zealand: High-surface-area textured implants are associated with increased risk. Plast Reconstr Surg 140:645-654, 2017.
7. Kinslow CJ, Yu JB, DeStephano DM, et al: Risk of squamous cell carcinoma of the breast following postmastectomy implant reconstruction in women with breast cancer and carcinoma in situ. JAMA Surg 158:769-771, 2023.
8. Kinslow CJ, Kim A, Sanchez GI, et al: Incidence of anaplastic large-cell lymphoma of the breast in the US, 2000 to 2018. JAMA Oncol 8:1354-1356, 2022.
9. Tandon VJ, DeLong MR, Ballard TN, et al: Evolving trends in textured implant use for cosmetic augmentation in the United States. Plast Reconstr Surg 142:1456-1461, 2018.
10. Kinslow CJ, DeStephano DM, Rohde CH, et al: Risk of anaplastic large cell lymphoma following postmastectomy implant reconstruction in women with breast cancer and ductal carcinoma in situ. JAMA Netw Open 5:e2243396, 2022.
Dr. Kinslow works in the Department of Radiation Oncology at the Vagelos College of Physicians and Surgeons, Columbia University, New York. Dr. Horowitz works in the Department of Radiation Oncology at Columbia University Irving Medical Center, New York. Dr. Neugut works in the Department of Medicine, Vagelos College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York.
