Garry S. Brody

The Relationship Between Breast Cancer and Augmentation Mammaplasty: An Epidemiologic Study

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age suggests that many such women may have a reduced amount of breast tissue, but data on this are unavailable.

Are breast implants anticarcinogenic? A 14-year follow-up of the Los Angeles Study.

Despite decades of use, the long-term safety of breast implants in women remains a concern. While the incidence of breast cancer among women has increased dramatically in the past decade, the implant-related risk of carcinoma of the breast only recently has received widespread attention. An additional concern is that the presence of the implant may delay tumor detection. This study allows examination of breast cancer risk and detection issues among patients with long-term exposure. We conducted a record linkage cohort study of cosmetic breast implant patients. We abstracted the records of the private practices of 35 broad-certified plastic surgeons in Los Angeles County, California. We included 3182 white women who received cosmetic breast implants between 1953 and 1980. Spanish-surnamed women, nonresidents of Los Angeles County, and patients with prior subcutaneous mastectomy or breast cancer were excluded. Cancer outcomes through 1991 have been ascertained through record linkage with the Los Angeles County Cancer Surveillance Program. With a median follow-up of 14.4 years, 31 breast cancer cases were observed, compared with 49.2 expected, based on Los Angeles County population-based incidence rates (standardized incidence ratio = 63.0 percent; 95 percent confidence limits: 42.8 and 89.5 percent). The distribution of stage of disease at diagnosis among women with implants did not differ from that of all similar breast cancer patients in Los Angeles County. In Los Angeles County, augmentation mammaplasty patients experience a significantly lower than expected risk of breast cancer and no delay in breast cancer detection after an average of 14.4 years of exposure. While the linkage methodology allows the possibility of failing to detect diagnosed cancer cases and does not permit collection of some pertinent risk factors, the six other published epidemiologic studies on the topic also report breast cancer risk to be at or below the expected rate.

Anaplastic Large Cell Lymphoma Occurring in Women with Breast Implants: Analysis of 173 Cases.

Background: The first silicone breast implant was inserted in 1962. In 1997, the first case of anaplastic large cell lymphoma (ALCL) in association with a silicone breast implant was reported. The authors reviewed 37 articles in the world literature reporting on 79 patients and collected another 94 unreported cases as of the date of submission. Methods: The world literature was reviewed. Missing clinical and laboratory information was solicited from the authors and treating physicians. As several different specialties were involved, information was not in one place. Many (but not all) authors and treating physicians were responsive, resulting in incomplete data. Results: ALCL lesions first presented as late peri-implant seromas, a mass attached to the capsule, tumor erosion through the skin, in a regional node, or discovered during revision surgery. The clinical course varied widely from a single positive cytology result followed by apparent spontaneous resolution, to disseminated treatment-resistant tumor and death. There was no preference for saline or silicone fill or for cosmetic or reconstructive indications. Where implant history was known, the patient had received at least one textured-surface device. Extracapsular dissemination occurred in 18 cases; nine of those were fatal. Histochemical markers were primarily CD-30+ and Alk-1−. Other markers occurred at a lower frequency. Risk estimates ranged from one in 500,000 to one in 3 million women with implants. Conclusion: Breast implant–associated ALCL is a novel manifestation of site- and material-specific lymphoma originating in a specific scar location, presenting a wide array of diverse characteristics and suggesting a multifactorial cause.

The surgical treatment of drooling. A ten-year review.

We report a 10-year experience with 123 patients who had the surgical treatment for drooling originally described by Wilkie. All have been followed for at least 1.5 years, and in 86 percent a good or excellent result was obtained. We believe this procedure is indicated for persistent, severe drooling in any patient in whom non-operative methods have failed, and for whom general anesthesia is an acceptable risk. Severe intellectual impairment is not a contraindication, for the care of these patients may be made far easier. Bilateral removal of the submandibular glands is an integral part of the operation on all patients, and should be done at the same time the parotid ducts are rerouted. The complications have been few and most of them respond to secondary procedures.

Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

Background: A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant–associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Methods: Twenty-six breast implant–associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Results: Both the breast implant–associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant–associated ALCL, 4.7 × 106 cells/mg of tissue; capsule, 4.9 × 106 cells/mg of tissue). Analysis of the microbiome in breast implant–associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p < 0.05). In contrast, significantly more Staphylococcus spp. were found associated with nontumor capsule specimens compared with breast implant–associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. Conclusions: This novel finding of bacterial biofilm and a distinct microbiome in breast implant–associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Breast cancer stage at diagnosis and survival among patients with prior breast implants.

Longstanding concern exists regarding the potential for women with breast implants to experience delayed detection of breast cancer. Furthermore, survival among cosmetic breast implant patients who subsequently develop breast cancer is a concern. Since 1976, this institution has monitored cancer incidence in a cohort of 3182 women who underwent cosmetic breast augmentation between 1959 and 1981. The distributions of stage at diagnosis and survival of the 37 women who subsequently developed in situ or invasive breast cancer were compared with the observed population distributions. The distribution of stage at diagnosis for cosmetic breast implant patients who subsequently developed breast cancer was virtually identical to that of all breast cancer patients in Los Angeles County who were of the same age and race, and were diagnosed during the same time period. Furthermore, the 5-year survival rate of the 37 patients did not differ from that which would be expected based on rates established by the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. These results suggest that cosmetic breast implant patients are not at increased risk of delayed detection of breast cancer, nor do they suffer a poorer prognosis when breast cancer does occur. Although the number of breast cancer patients in this study is small, the results are highly consistent with the existing epidemiologic evidence related to breast cancer detection and survival among breast implant patients. Although breast implant patients should continue appropriate breast cancer screening behavior, there seems to be no cause for alarm.

Managing late periprosthetic fluid collections (seroma) in patients with breast implants: a consensus panel recommendation and review of the literature.

Background: The goal of this consensus is to establish an algorithm for the management of patients who develop a late or delayed periprosthetic fluid collection. A work group of practicing plastic surgeons and device industry physicians met periodically by teleconference and discussed issues pertinent to the diagnosis and management of late periprosthetic fluid collections in patients with breast implants. Based on these meetings, treatment recommendations and a treatment algorithm were prepared in association with an editorial assistant. Method: The work group participants discussed optimal care approaches developed in their private practices and from evidence in the literature. Results: The consensus algorithm and treatment and management recommendations represent the consensus of the group. Conclusions: The group concluded that late periprosthetic fluid collection (arbitrarily defined as occurring ≥1 year after implant) is an infrequently reported occurrence (0.1 percent) after breast implant surgery and that, at a minimum, management should include clinically indicated ultrasound-guided aspiration of fluid, with appropriate cultures and cytologic testing. Further evaluation and additional treatment is recommended for recurrence of periprosthetic fluid collection after aspiration, or clinical suspicion of infection or neoplasia.

Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: Establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity†

Primary lymphomas of the breast are very rare (0.2‐1.5% of breast malignancies) and the vast majority (95%) are of B‐cell origin. Recently, 40 cases of clinically indolent anaplastic large‐cell kinase (ALK)‐negative, T‐cell, anaplastic, non‐Hodgkin lymphomas (T‐ALCL) have been reported worldwide.

Cancer risk among Los Angeles women with cosmetic breast implants

Background: As the first generation of women who received cosmetic breast implants ages, questions remain about cancer risk. This study is an update of the Los Angeles Augmentation Mammaplasty Study and examines cancer risk among women with long-term exposure to breast implants. Methods: The authors conducted a record linkage cohort study of patients with cosmetic breast implants by abstracting from records of the private practices of 35 board-certified plastic surgeons in Los Angeles County, California. They included 3139 Caucasian women who received cosmetic breast implants between 1953 and 1980. Spanish-surnamed women, nonresidents of Los Angeles County, and patients with prior subcutaneous mastectomy or breast cancer were excluded. Cancer outcomes through 1994 were ascertained through record linkage with the Los Angeles County Cancer Surveillance Program. Results: With a mean follow-up period of 15.5 years, 43 cases of breast cancer were observed, compared with 62.6 expected, based on Los Angeles County population-based incidence rates (standardized incidence ratio, 0.69; 95% CI, 0.50 to 0.93). Significant increases were observed for cancer of the lung and bronchus (standardized incidence ratio, 2.14; 95% CI, 1.42 to 3.09) and vulvar cancer (standardized incidence ratio, 3.47; 95% CI, 1.39 to 7.16). Conclusions: The breast cancer results of this study are consistent with the previous reports of the Los Angeles study as well as with several other long-term cohort studies. Lung cancer has previously been found to be increased in this cohort and also in some, but not most, other studies. The increased risk of vulva cancer has previously been observed in this cohort and just one other.

Biomarkers Provide Clues to Early Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Almost 200 women worldwide have been diagnosed with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The unique location and specific lymphoma type strongly suggest an etio-pathologic link between breast implants and BIA-ALCL. It is postulated that chronic inflammation via bacterial infection may be an etiological factor. BIA-ALCL resembles primary cutaneous ALCL (pcALCL) in morphology, activated T-cell phenotype, and indolent clinical course. Gene expression array analysis, flow cytometry, and immunohistochemistry were used to study pcALCL and BIA-ALCL cell lines. Clinical samples were also studied to characterize transcription factor and cytokine profiles of tumor cells and surrounding lymphocytes. BIA-ALCL and pcALCL were found to have common expression of transcription factors SOCS3, JunB, SATB1, and a cytokine profile suggestive of a Th1 phenotype. Similar patterns were observed in a CD30+ cutaneous lymphoproliferative disorder (LPD). The patterns of cytokine and transcription factor expression suggest that BIA-ALCL is likely to arise from chronic bacterial antigen stimulation of T-cells. Further analysis of cytokine and transcription factor profiles may allow early detection and treatment of BIA-ALCL leading to better prognosis and survival. LEVEL OF EVIDENCE 5: Risk.