SCOUT® Radar Localization at Time of Breast Biopsy.

OBJECTIVE: Evaluate surgical utilization of SCOUT reflectors placed at breast biopsy. METHODS: Consent was waived for this retrospective IRB-approved, HIPAA-compliant study. Breast biopsy examinations that reported the term "SCOUT" between January 2021 and June 2022 were identified using an institutional search engine. Cases were included if a SCOUT reflector was placed at time of breast biopsy and excluded if lesion pathology was already known. Analysis was performed at the lesion level. A multivariate-regression analysis evaluated 6 variables with potential impact on SCOUT utilization. RESULTS: One hundred twenty-one lesions in 112 patients met inclusion criteria. Biopsy yielded 93% (113/121) malignant, 3% (4/121) elevated risk, 2% (2/121) benign-discordant, and 2% (2/121) benign-concordant results. Two cases lost to follow-up were excluded. SCOUT reflectors were utilized for lumpectomy (58%, 69/119 lesions) and excisional biopsy (6%, 7/119 lesions). SCOUTs were not utilized due to mastectomy (23%, 27/119), subsequent wire localization (2%, 2/119), and nonsurgical cases (12%, 14/119). Reflector placement utilization was 52% higher for findings less than 3.5 cm in size (P <.001), 33% higher in patients without prior treated breast cancer (P = .012), and 19% higher in patients with no suspicious ipsilateral lymph node (P = .048). CONCLUSION: SCOUT reflector placement at time of biopsy was utilized for surgery 64% (76/119) of the time, although most (98%, 119/121) biopsies were malignant, elevated risk, or benign-discordant. Factors increasing reflector utilization include smaller lesion size, no suspicious ipsilateral lymph node, and no prior treated breast cancer.

A Novel Fat-Augmented Omentum-Based Construct for Unilateral and Bilateral Free-Flap Breast Reconstruction in Underweight and Normal Weight Women Receiving Nipple or Skin-Sparing Mastectomies.

BACKGROUND: Autologous tissue has proven advantages, however it is often not an option for women of low or normal body mass index (BMI). Omentum has been used sparingly, typically as a pedicled flap to correct breast deformities, but is considered suboptimal for full breast reconstruction. We developed a new construct, the omental fat-augmented free flap (O-FAFF) as an alternative for breast reconstruction. METHODS: O-FAFF involves laparoscopic omentum harvesting, creation of an acellular dermal matrix shell for its encasement, and lipoinjection to augment volume. The gastroepiploic vessels are microsurgically anastomosed to internal mammary vessels. Tissue and O-FAFF construct weights as well as outcomes are reported. RESULTS: Thirty-four consecutive women (50 breasts) received O-FAFF breast reconstruction after 18 unilateral and 16 bilateral mastectomies (10 non-nipple-sparing, 40 nipple-sparing). Thirty-seven were immediate and 13 were revisions of previous breast reconstructions. Patient mean age was 48.2 (range 23-73) years and mean BMI was 22.3 (range 17.6-32.4) kg/m2. Mean follow-up was 14.8 (range 3-33) months. The median weight of the omentum was 161.7 g (range 81-852, interquartile range [IQR] 102) and the mean ratio of fat to omentum weight was 0.73 (range 0.22-1.38) and 1.97 (range 0.24-3.8) for unilateral and bilateral cases, respectively. Postoperative pain scores and oral morphine equivalent consumption were more favorable for the O-FAFF group compared with controls (p < 0.001). Follow-up breast MRI demonstrated intact perfusion and no fat necrosis. CONCLUSIONS: The O-FAFF is ideally suited for women of lower BMI and could dramatically increase the number of women who are candidates for autologous breast reconstruction.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.

Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.

Patient perspectives on window of opportunity clinical trials in early-stage breast cancer.

PURPOSE: Window of opportunity trials (WOT) are increasingly common in oncology research. In WOT participants receive a drug between diagnosis and anti-cancer treatment, usually for the purpose of investigating that drugs effect on cancer biology. This qualitative study aimed to understand patient perspectives on WOT. METHODS: We recruited adults diagnosed with early-stage breast cancer awaiting definitive therapy at a single-academic medical center to participate in semi-structured interviews. Thematic and content analyses were performed to identify attitudes and factors that would influence decisions about WOT participation. RESULTS: We interviewed 25 women diagnosed with early-stage breast cancer. The most common positive attitudes toward trial participation were a desire to contribute to research and a hope for personal benefit, while the most common concerns were the potential for side effects and how they might impact fitness for planned treatment. Participants indicated family would be an important normative factor in decision-making and, during the COVID-19 pandemic, deemed the absence of family members during clinic visits a barrier to enrollment. Factors that could hinder participation included delay in standard treatment and the requirement for additional visits or procedures. Ultimately, most interviewees stated they would participate in a WOT if offered (N = 17/25). CONCLUSION: In this qualitative study, interviewees weighed altruism and hypothetical personal benefit against the possibility of side effect from a WOT. In-person family presence during trial discussion, challenging during COVID-19, was important for many. Our results may inform trial design and communication approaches in future window of opportunity efforts.

Creating a Biological Breast Implant with an Omental Fat-Augmented Free Flap.

SUMMARY: Women with inadequate myocutaneous or fasciocutaneous soft-tissue donor sites for breast reconstruction after mastectomy are mostly limited to implants. Alternative substitutes are needed for those who do not want-or in whom there are contraindications for-implant-based reconstruction. The authors report a novel technique using an omental fat-augmented free flap to create an autologous breast mound that has comparable shape and projection to a breast implant. Three patients with breast cancer who desired unilateral reconstruction were identified in the period 2019 to 2020. All had insufficient traditional autologous sites and were averse to the use of implants. A nipple-sparing mastectomy was performed, and the omentum was laparoscopically harvested and fat-grafted ex vivo and then encased in acellular dermal matrix for microvascular anastomoses. The body mass indexes of the three patients were 17.6, 25, and 28.3 kg/m2. Each individual's mastectomy specimens and corresponding omentum plus fat-grafting weights were 113.7/228, 271/293, and 270/360 g. No postoperative complications occurred. The reconstructed breast remains soft, with stable breast volume at 6 months and without evidence of fat necrosis. This novel use of fat grafting into an omental flap enveloped in acellular dermal matrix, the omental fat-augmented free flap, provides a viable and successful autologous alternative for patients who are not candidates for traditional autologous breast reconstruction options because of body habitus or personal preference.

Locally advanced breast cancer.

Locally advanced breast cancer (LABC) is defined here as inoperable breast adenocarcinoma without distant metastases. Patients with LABC require a multidisciplinary approach. Given the risk of distant metastasis, staging exams are necessary. The incidence of LABC (stages IIIB and IIIC) has decreased in recent years. LABC has rarely been investigated separately: patients with LABC have participated both in clinical trials of palliative and of neoadjuvant therapy. Most trials did not analyze responses and long-term outcomes independently; thus, the treatment of patients with LABC is extrapolated from studies of patients with less or more advanced disease. Pathologic confirmation and molecular profiling are essential for the choice of neoadjuvant chemotherapy. Preoperative endocrine therapy may be considered in certain clinical situations; the addition of a CDK4/6 inhibitor is being investigated. HER2 positive LABCs are targeted with anti-HER2 agents combined with chemotherapy. PD-1 and PD-L1 antibodies in 'triple-negative' LABC are promising. Excellent responses to neoadjuvant therapy enable conservative surgery in many patients; however, inflammatory breast cancer may still indicate mastectomy. Postoperative radiotherapy is usually indicated. Target volumes include breast/chest wall, axillary, supraclavicular and internal mammary nodal basins. Preoperative radiation therapy can be useful in patients without response to systemic therapies. Palliative surgery for poor responders after neoadjuvant systemic and radiation therapy can be considered. Multidisciplinary teams can optimize local control and prevent relapses. However, modest improvement in survival was achieved between 2000 and 2014 underscoring the unmet need in patients with LABC who will benefit from specific research efforts in this disease entity.

Maintaining Contour with a Three-dimensional Interstitial Tissue Marker in 134 Lumpectomies.

Breast-conserving surgery (BCS) is meant to preserve the natural appearance of the breast; however, tissue volume deficits cannot always be compensated by soft tissue mobilization. A three-dimensional (3D) interstitial tissue marker (BioZorb) was designed to delineate the lumpectomy cavity for targeting boost irradiation, but an unexpected secondary benefit may be in guiding wound contraction and restoring contour to the lumpectomy bed. We analyze tissue volume excised at the time of lumpectomy as a function of device size selected. METHODS: In total, 134 consecutive lumpectomy patients implanted with BioZorb between May 2015 and February 2020 were retrospectively analyzed for tissue volume excised, device size used, location, and re-operation rates, including explantation of the device. RESULTS: An estimated 113 patients underwent device implantation at initial lumpectomy, and 21 at margin re-excision. Twenty-seven patients underwent re-excision, while 14 elected mastectomy for positive margins following insertion; 22 had the same device reimplanted. Mean lumpectomy volume was 79.0 cm3 (range 10.3-275.8 cm3) during the first implant procedure. Large-volume lumpectomies, averaging 136.5 cm3, were associated with selection of larger devices, which aided in restoring volume and maintaining breast contour. Three (2.2%) patients requested removal of the device. CONCLUSIONS: BioZorb implantation can be a safe and useful oncoplastic technique for restoring volume with BCS. Large-volume lumpectomies can be performed without contouring defects using the device. An unexpected secondary benefit of the device may be scaffolding for wound contraction.

Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial.

Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.

Methotrexate in the Treatment of Idiopathic Granulomatous Mastitis.

OBJECTIVE: Idiopathic granulomatous mastitis (IGM) is a disfiguring inflammatory breast disease without effective treatment. We report the largest IGM cohort treated with methotrexate (MTX) monotherapy. METHODS: Chart review was performed on patients evaluated by the Stanford Immunology and Rheumatology Clinic, with histopathologically established IGM treated with MTX, and at least 1 followup appointment. RESULTS: Nineteen female patients with a mean age of 33.5 years were identified. Most failed treatment with antibiotics, prednisone, and surgical intervention. By 15 months of treatment with MTX, 94% had disease improvement and 75% achieved disease remission. CONCLUSION: MTX monotherapy is an effective treatment for IGM.

Dilemma in management of hemorrhagic myositis in dermatomyositis.

Dermatomyositis (DM) is a rare inflammatory disorder affecting the muscle and skin. DM patients can present with spontaneous muscle hemorrhage, a potentially fatal complication. The best practice for management of hemorrhagic myositis in these patients remains unclear. Here we discuss the case of a patient who presented with progressive muscle weakness and intermittent rash that was diagnosed with dermatomyositis. During admission, she developed spontaneous hemorrhagic myositis of the right pectoralis major treated with surgical evacuation. She also developed a spontaneous left anterior thigh hematoma which was treated conservatively. She recovered and showed no evidence of recurrent bleeding at either location. We performed a literature review and identified ten cases of spontaneous hemorrhage in DM patients, with a 60% mortality rate among reported cases. Given the high mortality rate associated with spontaneous hemorrhage in DM patients, it is important for physicians to be aware of the diagnosis, workup, and management strategies.

Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer.

Purpose There is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer. Methods We identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT. Results Of 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT. Conclusions PreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

Pretreatment Tattoo Marking of Suspicious Axillary Lymph Nodes: Reliability and Correlation with Sentinel Lymph Node.

BACKGROUND: Tattooing is an alternative method for marking biopsied axillary lymph nodes (ALNs) before initiation of treatments for newly diagnosed breast cancer. Detection of black ink-stained nodes is performed under direct visualization at surgery and is combined with sentinel node (SLN) mapping procedures. METHODS: Women with newly diagnosed breast cancer who underwent fine or core-needle biopsy of suspicious ALNs were recruited. The nodal cortex and perinodal soft tissue was injected with 0.1-1.0 ml of Spot™ (GI Supply) black ink under ultrasound guidance. Intraoperatively, black stained nodes were removed along with SLNs, noting concordance between the two. RESULTS: Sixty-six evaluable patients were enrolled (2013-2017). Nineteen received surgery first (Group 1) and 47 neoadjuvant therapy (NAT, Group 2). The average number of nodes tattooed was 1.16 for Group 1 and 1.04 for Group 2. The average interval from tattoo to surgery was 21 days (range 1-62) for Group 1 and 148 days (range 71-257) for Group 2. The tattooed node(s) were visually identified at surgery and corresponded to the sentinel lymph node(s) in 98.5% of cases (18/19 in Group 1 and 47/47 in Group 2). Of the 14 patients in Group 2 whose nodes remained positive following NAT, the tattooed node was the SLN associated with carcinoma. CONCLUSIONS: Tattooing is an alternative method for marking biopsied ALNs. Tattooed nodes coincided with SLNs in 98.5% of cases. This technique is advantageous, because it allows for fewer procedures and lower costs compared with other methods.

Current Strategies for the Management of Locoregional Breast Cancer Recurrence.

Advances in the treatment of breast cancer have decreased the rate of isolated locoregional recurrences (ILRRs) over time. Surgery, radiation therapy, and systemic therapies are used to manage these failure events and their associated poor prognosis. Operable ipsilateral breast tumor recurrences (IBTRs) are treated by either salvage mastectomy or, in select cases, repeat lumpectomy. Axillary nodal recurrences and postmastectomy chest wall relapses are commonly amenable to surgical resection, too. Repeat sentinel node mapping may be undertaken after IBTRs and chest wall recurrences. Aberrant lymphatic drainage, especially after previous mastectomy, is frequently observed. Adjuvant radiation is recommended for most ILRR cases; the dose and volume must be adjusted for prior to receipt of therapy. Implementation of adjuvant systemic therapies after ILRR should be based on the expression of molecular markers in the recurrent tumor. Administration of chemotherapy for estrogen receptor-negative ILRR is indicated, since it significantly decreases the rate of distant metastases.

The Impact of Device Innovation on Clinical Outcomes in Expander-based Breast Reconstruction.

Staged expander-based breast reconstruction represents the most common reconstructive modality in the United States. The introduction of a novel tissue expander with an integrated drain (Sientra AlloX2) holds promise to further improve clinical outcomes. METHODS: Patients who underwent immediate expander-based pre-pectoral breast reconstruction were identified. Two cohorts were created, that is, patients who underwent placement of a conventional tissue expander [133MX (Allergan)] (Group 1) versus AlloX2 (Sientra) (Group 2). The study endpoint was successful completion of expansion with the objective being to investigate differences in outcome following expander placement. RESULTS: Fifty-eight patients underwent 99 breast reconstructions [Group 1: N = 24 (40 breasts) versus Group 2: N = 34 (59 breast)]. No differences were noted for age (P = 0.586), BMI (P = 0.109), history of radiation (P = 0.377), adjuvant radiotherapy (P = 1.00), and overall complication rate (P = 0.141). A significantly longer time to drain removal was noted in Group 1 (P < 0.001). All patients with postoperative infection in Group 1 required surgical treatment versus successful washout of the peri-prosthetic space via the AlloX2 drain port in 3 of 5 patients in Group 2 (P = 0.196). Furthermore, both cases of seroma in Group 1 required image-guided drainage versus in-office drainage via the AlloX2 drain port in 1 patient in Group 2 (P =0.333). CONCLUSION: The unique feature of the AlloX2 provides surgeons easy access to the peri-prosthetic space without altering any of the other characteristics of a tissue expander. This resulted in a reduced time to drain removal and facilitated management of postoperative seroma and infection.

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.

BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause). RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone. CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).