Breast Implant-associated Anaplastic Large Cell Lymphoma: A Prospective Series of 52 Patients.

OBJECTIVE: We sought to evaluate patients at a single academic institution in a prospective manner to report patient presentation, clinical course, treatment, and outcomes in breast implant ALCL patients. BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) is an uncommon T cell lymphoma, which is associated with textured surface breast implants. The disease has received increasing attention over the last 20 years. Previous retrospective studies have begun to outline the clinical course of breast implant ALCL. METHODS: We prospectively followed women with cytologically proven breast implant ALCL from 2014 to 2019. Demographic, clinical, treatment, and outcome data were collected and descriptive statistics were performed on variables of interest. RESULTS: We identified 52 women with pathologically confirmed breast implant ALCL. Implants were placed for augmentation in 61.5% of women and reconstruction in 36.5% of women. All of the 41 patients with known implant information had implants with textured surface. The majority of patients presented with delayed seroma (69.2%) and without systemic symptoms (86.5%). Most patients with staging information presented with Stage IA disease. Patient outcomes were excellent with 2 disease recurrence (3.8%) and all patients ultimately achieved complete remission. CONCLUSIONS: Further evaluation of the prospective and growing database of patients with breast implant ALCL will further improve our understanding of the disease and its clinical course. Robust participation in the breast implant ALCL PROFILE registry will improve our knowledge of long-term outcomes after implant placement. Finally, increasing awareness for patients and providers will lead to earlier diagnosis and improved outcomes for patients.

Differences in Human Leukocyte Antigen Expression Between Breast Implant-Associated Anaplastic Large Cell Lymphoma Patients and the General Population.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma associated with textured-surface breast implants. Human leukocyte antigen (HLA) polymorphisms have been described with other forms of lymphoma, but have not been described for BIA-ALCL. OBJECTIVES: The aim of this study was to evaluate HLA polymorphisms in BIA-ALCL patients. METHODS: We prospectively evaluated HLA alleles in patients with BIA-ALCL. HLA was analyzed by probe-based sequence-specific testing and sequence-based typing. The frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles were evaluated. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program to serve as normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals from a t test. RESULTS: Thirteen patients who had undergone BIA-ALCL and HLA testing were identified from 2017 to 2018. Patients carried 10, 11, and 9 HLA-A, HLA-B, and HLA-C alleles, respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The A*26 allele occurred significantly more frequently in the general population compared with BIA-ALCL patients (0.2992 vs 0.07692, P < 0.001). CONCLUSIONS: Our results identify a difference between HLA A*26 in patients who develop BIA-ALCL and the general population, and may signify genetic susceptibility factors responsible for germline genetic variation in HLA in patients with BIA-ALCL. Further work is needed to elucidate if these alleles are predictive for BIA-ALCL in women with textured-surface breast implants.Level of Evidence: 4.

Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial.

Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P = .96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P = .73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.

Stepwise En Bloc Resection of Breast Implant-Associated Anaplastic Large Cell Lymphoma with Oncologic Considerations.

Guidelines published by the National Comprehensive Cancer Network state that standard of care treatment for the majority of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is surgical resection. This cancer is generally indolent, and if confined to the capsule, curative treatment is usually surgery alone. An en bloc resection involves a total capsulectomy, explantation, complete excision of associated masses, and excision of any involved lymph node(s). Patients with surgical control of disease have favorable long-term overall and event-free survival. Oncologic principles should be applied when resecting BIA-ALCL, and a complete oncologic resection is essential to cure patients of the disease. Incomplete resections, partial capsulectomies, and positive margins are all associated with high rates of disease recurrence and have potential for progression of the disease. Routine sentinel lymph node biopsy is unnecessary and full axillary lymph node dissection is rarely indicated except in cases of proven involvement of multiple nodes. Lymphoma oncology consultation and disease staging by imaging is performed prior to surgery. Importantly, en bloc resection is indicated only for an established diagnosis of BIA-ALCL, and is not recommended for merely suspicious or prophylactic surgeries. The purpose of this article was to demonstrate a stepwise approach to surgical ablation of BIA-ALCL with an emphasis on oncologic considerations critical to disease prognosis.

Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial.

BACKGROUND: Neoadjuvant chemotherapy with trastuzumab for patients with HER2-positive breast cancer can produce a pathological complete response in the breast in 30-65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. METHODS: This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. FINDINGS: From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56·5%, 95% CI 47·8-64·9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54·2%, 95% CI 45·7-62·6) who received concurrent treatment (difference 2·3%, 95% CI -9·3 to 13·9). No treatment-related deaths occurred. The most common severe toxic effects were neutropenia (35 [25·3%] of 138 patients in the sequential group vs 45 [31·7%] of 142 patients in the concurrent group) and fatigue (six [4·3%] vs 12 [8·5%]). Left ventricular ejection fraction dropped below the institutional lower limit of normal at week 12 in one (0·8%) of 130 patients who received sequential treatment and four (2·9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7·1%) of 126 patients and in six (4·6%) of 130 patients, respectively. INTERPRETATION: Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted. FUNDING: US National Cancer Institute.