Disaggregating the Asian-American Breast Cancer Population: Disparities in Reconstruction Rates.

INTRODUCTION: Breast cancer (BC) incidence has been increasing among Asian-Americans (AsAms); recent data suggest these patients are less likely to undergo postmastectomy breast reconstruction (PMBR) compared to non-Asian women. Historically, AsAm BC patients are reported in aggregate, masking heterogeneity within this population. We aim to identify patterns of postmastectomy reconstruction among disaggregated AsAm BC patients at our institution. METHODS: A retrospective chart review was performed for BC patients who underwent mastectomy between 2017 and 2021. Patient demographic and clinical information was collected including self-reported race/ethnicity and reconstruction at time of mastectomy. Self-identified Asian patients were disaggregated into East Asian, Southeast Asian, South Asian, and 'Asian Other.' We examined rates of reconstruction between the different races and the disaggregated Asian subgroups. Univariable and multivariable analysis was performed to examine patient factors associated with PMBR. RESULTS: Six hundred and five patients met inclusion criteria. Forty seven percent of patients identified as Asian, 36% of which as East Asian. Forty four percent of all patients underwent PMBR. Southeast Asian and South Asian women were least likely to undergo reconstruction, while Hispanic and non-Hispanic Black women were most likely to pursue PMBR (P = 0.020). On multivariable analysis, Hispanic, non-Hispanic White, and non-Hispanic Black women were more likely to undergo reconstruction compared to Asian women. Other factors associated with reconstruction were coverage with private insurance and diagnosis of noninvasive disease. CONCLUSIONS: Rates of PMBR are lower among AsAms than non-Asian patients and vary between Asian ethnic subgroups. Further investigation is needed to identify patterns of reconstruction among the disaggregated AsAm population to address disparities.

Comparisons of Impact of Vein Grafting with Different Indications on Outcomes of Reconstruction with Free Flaps.

BACKGROUND: Prior studies have shown an increased risk of complications and flap loss with the use of vein grafts in microsurgery. We hypothesize that indication for use of a vein graft can affect flap complications and loss rates. METHODS: We performed a retrospective review of all patients at our institution from 2010 to 2020 who underwent free flap reconstruction and required use of a vein graft. Indications for vein grafting included: salvage of flap during primary operation after microvascular compromise, augmentation of flow during primary operation, lengthening of the flap pedicle during the primary operation, and salvage of the flap during a secondary salvage operation after microvascular compromise. RESULTS: A total of 79 patients met the study inclusion criteria. There were significant differences among the vein graft indication groups and the following: area of reconstruction (p = 0.002), vein graft length (p = 0.018), vessels grafted (p = 0.001), vein graft donor site (p = 0.011), and total flap loss (p = 0.047). Of the four indications for vein grafting, salvage of the flap during secondary salvage operation after microvascular compromise had the highest rate of total flap loss (26.7%). There were no significant associations between other flap complications and vein graft indications. CONCLUSION: Vein graft use in the primary reconstructive setting is efficacious, with low risk of thrombosis. Use in secondary procedures, however, is associated with higher rates of total flap loss, likely due to the thrombotic process, which was initiated prior to the use of the graft resulting in the salvage procedure and not secondary to the graft itself.

The Impact of Lymphedema on Patient-Reported Outcomes After Breast Reconstruction: A Preliminary Propensity Score-Matched Analysis.

BACKGROUND: Studies on the impact of secondary lymphedema on patient-reported satisfaction and quality of life following postmastectomy breast reconstruction are limited by their heterogeneity. We aimed to reduce heterogeneity in study sample populations and compare BREAST-Q Reconstruction Module scores of patients with lymphedema matched to patients without lymphedema. METHODS: We identified patients who underwent postmastectomy breast reconstruction from 2009 to 2017 and performed a propensity score-matched analysis to compare patient-reported outcomes of patients who developed lymphedema with those who did not. Matched covariates included age, body mass index, race/ethnicity, smoking history, radiation or chemotherapy exposure, postoperative infection, and reconstruction modality and laterality. Outcomes of interest were pre- and postoperative BREAST-Q scores for Satisfaction with Breasts, Physical Well-being of the Chest, Sexual Well-Being, and Psychosocial Well-Being; the minimal clinically important difference (MCID) was four points. RESULTS: Matched cohorts included 322 patients per group. Preoperative BREAST-Q scores did not differ between lymphedema and non-lymphedema matched cohorts. Postoperative BREAST-Q scores were significantly lower in lymphedema patients: Physical Well-Being of the Chest (all time points), Satisfaction with Breast (at 1 and 2 years), Sexual Well-Being (at 2 years), and Psychosocial Well-Being (at 2 and 3 years). All significant differences in average scores were greater than the MCID. CONCLUSIONS: Patients with breast cancer-related lymphedema reported significantly lower Physical Well-Being of the Chest, Satisfaction with Breasts, Sexual Well-Being, and Psychosocial Well-Being at various time points. Our findings may prove useful for patient counseling and justify the need for further research on the prevention and treatment of this devastating disease.

An updated systematic review of esthetic grading tools in postmastectomy breast reconstruction.

BACKGROUND AND OBJECTIVES: We ascertained whether a validated esthetic grading tool for breast reconstruction had been developed and widely adopted since the last published systematic review on the topic from 2015. METHODS: We performed a systematic review identifying all studies using a grading tool to assess breast reconstruction, using search terms associated with all types of breast surgery and outcomes research. Articles were assessed for patient number, validated scale use, assessor type and training, assessor blinding, assessment method, scoring system type, type and timing of reconstruction, and usage of corroborating scales. RESULTS: Of 2809 articles screened, 148 met the criteria. Only 3 used a validated tool, the Esthetic Items Scale. Most used study-only tools (n = 111) or unvalidated tools (n = 28). The most used unvalidated tool was the Garbay/Lowery 5-subscale rubric. Unanchored Likert scales were the most common subjective tool; two-dimensional images were the most used medium. Surgeons, patients, and nurses were the most common assessors. Twenty percent of studies used corroborating scales. CONCLUSIONS: In the absence of a validated esthetic grading tool for breast reconstruction, researchers continue to rely on unvalidated scales. The only validated scale available is used infrequently and only validated among physicians. A validated, reliable, simple grading tool with clinical and scholastic relevance is needed.

Accuracy, Sensitivity, and Specificity of the LLIS and ULL27 in Detecting Breast Cancer-Related Lymphedema.

INTRODUCTION: Breast cancer-related lymphedema occurs in up to 30% of women following axillary lymph node dissection (ALND) and less commonly following sentinel lymph node biopsy. To quantify disability in these patients, patient-reported outcome measures (PROMs) have proven useful; however, given the overlap of symptoms between ALND and lymphedema, examination of their accuracy, sensitivity, and specificity in detecting lymphedema in breast cancer patients undergoing ALND is needed. METHODS: The Lymphedema Life Impact Scale (LLIS) and the Upper Limb Lymphedema 27 scale (ULL27) were administered to patients who had undergone ALND at least 2 years prior and either did or did not develop lymphedema. Survey responses and the degree of disability were compared to generate receiver operator characteristic (ROC) curves, and the sensitivity and specificity of PROMs to diagnose lymphedema were analyzed. RESULTS: Both PROMs were highly accurate, sensitive, and specific for detecting lymphedema. The LLIS had an accuracy of 97%, sensitivity of 100%, and specificity of 84.8% at a cutoff of ≥ 5.88 overall percent impairment score (higher scores indicate worse disability). The ULL27 had an accuracy of 93%, sensitivity of 88.6%, and specificity of 90.9% at a cutoff of ≤ 83.3 global score (lower scores indicate worse disability). CONCLUSIONS: The LLIS and the ULL27 appear to be highly specific for lymphedema and capable of differentiating it from symptoms resulting from ALND alone. Our findings suggest that use of these questionnaires with a threshold may be effective for diagnosing lymphedema, potentially reducing the need for frequent clinic visits and time-consuming measurements.

Noninvasive Systemic Modalities for Prevention of Head and Neck Radiation-Associated Soft Tissue Injury: A Narrative Review.

BACKGROUND: Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as xerostomia, which requires frequent daily maintenance, to destructive degenerative processes such as osteoradionecrosis, which can contribute to flap failure and delay or reverse oral rehabilitation. Despite the need for effective radioprotectants, the literature remains sparse, primarily focused on interventions beyond the surgeon's control, such as maintenance of good oral hygiene or modulation of radiation dose. METHODS: This narrative review aggregates and explores noninvasive, systemic treatment modalities for prevention or amelioration of radiation-associated soft tissue injury. RESULTS: We highlighted nine modalities with the most clinical potential, which include amifostine, melatonin, palifermin, hyperbaric oxygen therapy, photobiomodulation, pentoxifylline-tocopherol-clodronate, pravastatin, transforming growth factor-ß modulators, and deferoxamine, and reviewed the benefits and limitations of each modality. Unfortunately, none of these modalities are supported by strong evidence for prophylaxis against radiation-associated soft tissue injury. CONCLUSION: While we cannot endorse any of these nine modalities for immediate clinical use, they may prove fruitful areas for further investigation.

Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience.

BACKGROUND: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor-positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. PATIENTS AND METHODS: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. RESULTS: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. CONCLUSIONS: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.

Bilateral Breast Reduction Without Opioid Analgesics: A Comparative Study.

BACKGROUND: Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. OBJECTIVES: This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. METHODS: A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. RESULTS: When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P < 0.05), fewer unplanned hospital admissions (P < 0.05), and highly significant decrease in postoperative opioid use (P < 0.001). CONCLUSIONS: This multimodal approach allows patients to safely undergo opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. LEVEL OF EVIDENCE: 3.

Positive Outcomes and Surgical Strategies for Bilateral Cochlear Implantation in a Child With X-Linked Deafness.

OBJECTIVES: To recognize that bilateral cochlear implantation (CI) in X-linked deafness is safe, describe techniques to maximize successful electrode placement and minimize surgical risks, and recognize that normalization of hearing as well as language acquisition is achievable. METHODS: A 6-month-old male patient presented with bilateral profound sensorineural hearing loss and was confirmed to have X-linked deafness secondary to POU3F4 gene mutation. Due to lack of benefit from amplification, he underwent bilateral CI in a staged fashion at 12 (right) and 15 months (left) of age. A transmastoid-facial recess approach was used bilaterally utilizing perimodiolar electrodes. High-flow gushers were controlled with muscle plugs. C-arm fluoroscopy was used during insertion of electrodes. RESULTS: Follow-up data are available for 12 months. No complications were encountered, including no postoperative cerebrospinal fluid (CSF) leakage or facial stimulation. Postoperative audiograms in aided conditions showed hearing thresholds <40 dB. At 11 months following activation of his second CI, he scored in the normal range for his chronological age on standardized language measures. CONCLUSION: With careful preparation and the assistance of intraoperative fluoroscopy, CI in patients with congenital X-linked deafness can be done safely. Performing bilateral CI followed by dedicated auditory-verbal rehabilitation may allow patients to achieve normal language development.

Spreader Grafts in Functional Rhinoplasty.

Management of the middle vault is paramount to achieving optimal aesthetic and functional outcomes in rhinoplasty. The ideal treatment for middle vault complications, such as internal nasal valve collapse, inverted-V deformity, and middle vault dorsal asymmetry, is prevention. Risk factors for middle vault problems in rhinoplasty that may be identified in preoperative consultation include short nasal bones, long and weak upper lateral cartilages, thin skin, previous trauma or surgery, preoperative positive Cottle maneuver, tension nose deformity, and anteriorly positioned inferior turbinates. When any of these risk factors are identified, preventive measures should be pursued. These include preservation of middle vault support structures, judicious resection in dorsal hump reduction, use of conservative osteotomies, and reconstruction of the cartilaginous middle vault with structural grafting. Spreader grafts have become the workhorse in middle vault reconstruction. They are invaluable in restoring nasal dorsal aesthetic lines, repairing or maintaining the internal nasal valve, and buttressing a corrected crooked nose. Functional and aesthetic problems related to the middle nasal vault are among the most common reasons for patients seeking revision rhinoplasty. Although complications in rhinoplasty are inevitable, underlying their etiology and instituting prophylactic treatment can significantly help reduce their occurrence.

Male Rejuvenation: Injectables.

The use of injectables can effectively treat the areas of greatest facial esthetic concern in males. Due to significant differences in the facial anatomy of men compared to women, treatment strategy, dosage, and technique differs. This article will review the pharmacology, preparation, pertinent anatomy, technique, risks, and adverse events associated with injectable agents emphasizing unique differences in male anatomy and esthetics.

Prevention and Management of Complications in Nasal Reconstruction.

Nasal reconstruction is a challenging practice with the potential for complications. Surgeons can prevent complications through preoperative optimization of patient factors, refinement of intraoperative surgical techniques, and postoperative surgical and nonsurgical wound care. Preoperatively, optimization of modifiable and recognition of nonmodifiable risk factors is paramount. Intraoperatively, meticulous flap design and surgical technique promote healing. In the postoperative setting, attentive wound care, adjuvant therapies, and close follow-up for consideration of additional procedures enhance outcomes. By anticipating potential complications across perioperative settings, surgeons can prevent common complications in nasal reconstruction and more effectively manage those complications that arise.

Tandem Reconstruction of the Femoral Diaphysis Using an Intercalary Prosthesis and a Fibular Free Flap.

BACKGROUND: Femoral diaphyseal reconstructions with metal prostheses have mediocre results because of high mechanical forces that result in eventual implant failure. Biological alternatives require prolonged restrictions on weight-bearing and have high rates of infection, nonunion, and fracture. A novel method of utilizing a vascularized fibula in combination with an intercalary prosthesis was developed to complement the immediate stability of the prosthesis with the long-term biological fixation of a vascularized fibular graft. METHODS: A prospectively maintained database was retrospectively reviewed to identify patients who underwent reconstruction of an oncological intercalary femoral defect using an intercalary prosthesis and an inline fibular free flap (FFF). They were compared with patients who underwent femoral reconstruction using an intercalary allograft and an FFF. RESULTS: Femoral reconstruction with an intercalary metal prosthesis and an FFF was performed in 8 patients, and reconstruction with an allograft and an FFF was performed in 16 patients. The mean follow-up was 5.3 years and 8.5 years, respectively (p = 0.02). In the bioprosthetic group, radiographic union of the fibula occurred in 7 (88%) of 8 patients, whereas in the allograft group, 13 (81%) of 16 patients had allograft union (p = 1.00) and all 16 patients had fibular union (p = 0.33). The mean time to fibular union in the bioprosthetic group was 9.0 months, whereas in the allograft group, the mean time to allograft union was 15.3 months (p = 0.03) and the mean time to fibular union was 12.5 months (p = 0.42). Unrestricted weight-bearing occurred at a mean of 3.7 months in the prosthesis group and 16.5 months in the allograft group (p < 0.01). Complications were observed in 2 (25%) of 8 patients in the prosthesis group and in 13 (81%) of 16 patients in the allograft group (p = 0.02). Neither chemotherapy nor radiation affected fibular or allograft union rates. Musculoskeletal Tumor Society scores did not differ significantly between the groups (mean, 26 versus 28; p = 0.10). CONCLUSIONS: Bioprosthetic intercalary femoral reconstruction with a metal prosthesis and an FFF resulted in earlier weight-bearing, a shorter time to union, fewer operations needed for union, and lower complication rates than reconstruction with an allograft and an FFF. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Osseous Maxillary Reconstruction with Immediate Dental Implant Placement: An Optimized Workflow for the Oncologic Patient.

INTRODUCTION: Maxillary reconstruction is a complex undertaking characterized by a 3-dimensional surgical site with deficiencies in multiple tissue types. Prior to virtual surgical planning(VSP), bony reconstruction was inaccurate and inefficient, thus reconstructions defaulted to soft tissue flaps or obturators. The current study describes an efficient and accurate approach to bony maxillary reconstruction with immediate dental implant placement(IDIP). METHODS: A reconstructive workflow was developed for osseous reconstruction to improve functional and aesthetic outcomes. Critical aspects include VSP, 3-D printed plates and IDIP. Review of a prospectively maintained database identified patients who underwent osseous maxillary reconstruction with a fibula flap and immediate dental implants from 2017-2022, with a focus on oncologic characteristics and reconstructive outcomes. RESULTS: During the study, 20 patients underwent maxillary reconstruction with VSP and IDIP. One dental implant out of 55 failed to osseointegrate and no flaps were lost. Three patients suffered partial loss of the fibula skin island; one required palatal closure with a radial forearm flap, and two were managed with outpatient debridement. Fifteen patients achieved either an interim or final retained dental prosthesis. All prostheses achieved acceptable aesthetic results without the instability associated with non-bone borne devices(e.g.dentures/obturators). No patients experienced delays in oncologic treatment. CONCLUSIONS: VSP technology has enabled surgeons to replace like with like to achieve better outcomes with acceptable morbidity for maxillary defects. IDIP provides all patients an opportunity for a fixed prosthesis even though not all complete the process. This maxillary reconstruction workflow can be safely accomplished in oncologic patients with promising and effective early results.

Beta-HPV 5 and 8 E6 promote p300 degradation by blocking AKT/p300 association.

The E6 oncoprotein from high-risk genus alpha human papillomaviruses (α-HPVs), such as HPV 16, has been well characterized with respect to the host-cell proteins it interacts with and corresponding signaling pathways that are disrupted due to these interactions. Less is known regarding the interacting partners of E6 from the genus beta papillomaviruses (ß-HPVs); however, it is generally thought that ß-HPV E6 proteins do not interact with many of the proteins known to bind to α-HPV E6. Here we identify p300 as a protein that interacts directly with E6 from both α- and ß-HPV types. Importantly, this association appears much stronger with ß-HPV types 5 and 8-E6 than with α-HPV type 16-E6 or ß-HPV type 38-E6. We demonstrate that the enhanced association between 5/8-E6 and p300 leads to p300 degradation in a proteasomal-dependent but E6AP-independent manner. Rather, 5/8-E6 inhibit the association of AKT with p300, an event necessary to ensure p300 stability within the cell. Finally, we demonstrate that the decreased p300 protein levels concomitantly affect downstream signaling events, such as the expression of differentiation markers K1, K10 and Involucrin. Together, these results demonstrate a unique way in which ß-HPV E6 proteins are able to affect host-cell signaling in a manner distinct from that of the α-HPVs.

Accessory Lymphatic Drainage Pathways on Indocyanine Green Lymphography in Patients with Breast Cancer-Related Lymphedema.

BACKGROUND: Current predictive models of lymphedema risk cannot predict with 100% certainty which patients will go on to develop lymphedema and which will not. Patient-specific anatomic and physiologic differences may be the missing factor. The authors hypothesize that patients with accessory lymphatic pathways may have improved lymphatic drainage, resulting in smaller limb volumes. METHODS: The authors reviewed indocyanine green (ICG) lymphography images of all patients who presented to their institution for evaluation of breast cancer-related lymphedema. Patients with unilateral upper extremity lymphedema, a full set of bilateral limb measurements, and ICG images of both limbs were included. Other variables of interest included patient demographics and length of follow-up. Patients with accessory pathways were determined independently, and conflicts were resolved with discussion. Abnormal images were also evaluated for common drainage pathways. RESULTS: Thirty patients were identified as having accessory lymphatic drainage pathways. These patients had significantly smaller limb volume differences [8.19% (SD, 11.22)] compared with patients who did not exhibit these pathways [20.74% (SD, 19.76); P < 0.001]. The most common pathway was absence or rerouting of the radial bundle to the ulnar or volar bundles ( n = 16). CONCLUSIONS: The ability to create accessory lymphatic drainage pathways may be associated with improved lymphatic drainage, resulting in smaller limb volumes. Furthermore, certain drainage pathways appear to be more common than others. Description of these pathways should be considered for inclusion in ICG lymphography image grading criteria. Further study is needed to clarify the nature of these pathways and whether these pathways affect subjective symptoms and quality of life. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Multiple Cutaneous Solitary Circumscribed Neuroma in a Patient with Neurofibromatosis Type 2: An "Incidentaloma" or New Association?

Solitary circumscribed neuroma formerly known as palisaded encapsulated neuroma is a rare, benign neural tumor that usually presents as a painless firm nodule or papule on the face and within oral cavity, although they can occur elsewhere on the body. No association with neurofibromatosis has been reported in the literature. Herein, we report, a previously unreported unique association of neurofibromatosis type 2 (NF-2) with multiple cutaneous solitary circumscribed neuromas in a 24-year-old female. A 24-year-old female with history of NF-2 presented with two slow-growing soft-to-firm papules on the chin and forehead that had been gradually increasing in size over a period of 5 years. The papule on the chin was increasingly tender to palpation. Histologic sections demonstrated a dermal based almost encapsulated, smoothly contoured tumefactive mass composed of spindle cell proliferation with neuroid structures and foci of palisaded growth (resembling schwannoma) and intralesional cleft like spaces. By immunohistochemistry, the lesional cells were strongly and diffusely positive for S-100 and SOX10 with multifocal neurofilament expression while the "capsule" was diffusely reactive for epithelial membrane antigen. The overall features were considered prototypic for solitary circumscribed neuroma. The patient is 18-months post-surgical resection with no evidence of recurrence. In summary, we report for the first time a case of multiple solitary circumscribed neuromas in a patient with known NF2. We highlight pertinent diagnostic clues relevant to surgical pathologist to facilitate recognition (as this tumor is often mistaken for schwannoma or neurofibroma). The clinical behavior is excellent and surgical resection is considered curative.

A Gene Panel Associated With Abemaciclib Utility in ESR1-Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression.

PURPOSE: For patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), first-line treatment is endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibition (CDK4/6i). After disease progression, which often comes with ESR1 resistance mutations (ESR1-MUT), which therapies to use next and for which patients are open questions. An active area of exploration is treatment with further CDK4/6i, particularly abemaciclib, which has distinct pharmacokinetic and pharmacodynamic properties compared with the other approved CDK4/6 inhibitors, palbociclib and ribociclib. We investigated a gene panel to prognosticate abemaciclib susceptibility in patients with ESR1-MUT MBC after palbociclib progression. METHODS: We examined a multicenter retrospective cohort of patients with ESR1-MUT MBC who received abemaciclib after disease progression on ET plus palbociclib. We generated a panel of CDK4/6i resistance genes and compared abemaciclib progression-free survival (PFS) in patients without versus with mutations in this panel (CDKi-R[-] v CDKi-R[+]). We studied how ESR1-MUT and CDKi-R mutations affect abemaciclib sensitivity of immortalized breast cancer cells and patient-derived circulating tumor cell lines in culture. RESULTS: In ESR1-MUT MBC with disease progression on ET plus palbociclib, the median PFS was 7.0 months for CDKi-R(-) (n = 17) versus 3.5 months for CDKi-R(+) (n = 11), with a hazard ratio of 2.8 (P = .03). In vitro, CDKi-R alterations but not ESR1-MUT induced abemaciclib resistance in immortalized breast cancer cells and were associated with resistance in circulating tumor cells. CONCLUSION: For ESR1-MUT MBC with resistance to ET and palbociclib, PFS on abemaciclib is longer for patients with CDKi-R(-) than CDKi-R(+). Although a small and retrospective data set, this is the first demonstration of a genomic panel associated with abemaciclib sensitivity in the postpalbociclib setting. Future directions include testing and improving this panel in additional data sets, to guide therapy selection for patients with HR+/HER2- MBC.