ABSTRACT
Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.
Subject(s)
Breast Neoplasms , Mastectomy , Humans , Female , Mastectomy/methods , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Neoadjuvant Therapy/methods , Prospective Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Mastectomy, Segmental , Chemotherapy, Adjuvant/methods , Retrospective StudiesABSTRACT
BACKGROUND: Invasive lobular carcinoma (ILC) of the breast is known for high risk of late recurrence, yet some patients still recur within 5 years of diagnosis. Determining factors associated with early/late recurrence could help tailor treatment and surveillance strategies. METHODS: Using an institutional database, we evaluated patients with ILC and ≥ 5 years of follow-up or recurrence within 5 years. We used multivariate logistic regression and the Kaplan-Meier method to evaluate which clinicopathologic features and treatment strategies were associated with recurrence < 5 years since diagnosis versus recurrence ≥ 5 years since diagnosis. Additionally, we explored the association between Clinical Treatment Score 5 (CTS5) with early versus late recurrence. RESULTS: Among 513 cases of stage I-III ILC, there were 75 early and 54 late recurrences during a median follow-up period of 9.4 years. Early recurrence was associated with larger tumors (mean 4.2 cm vs. 2.9 cm, p < 0.0001), higher incidence of > 3 positive nodes (32.4% vs. 9.11%, p > 0.0001), and more aggressive tumor biology (low/negative progesterone receptor expression, higher grade, and higher Ki67). Late recurrence was associated with younger age (mean 55.6 vs. 59.2 years, p = 0.037) and elevated body mass index (BMI > 25 kg/m2 in 60.1.0% vs. 45.4%, p = 0.021). Omission of adjuvant endocrine therapy or radiotherapy after lumpectomy conferred increased risk of early rather than late recurrence. CONCLUSION: Factors related to tumor aggressiveness and treatment were associated with early recurrence, whereas patient related factors were related to late recurrence. These data may help guide treatment strategies and surveillance approaches for patients with ILC.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Lobular , Humans , Female , Carcinoma, Lobular/pathology , Breast Neoplasms/pathology , Mastectomy, Segmental , Combined Modality Therapy , Carcinoma, Ductal, Breast/pathology , Neoplasm Recurrence, Local/therapy , Retrospective StudiesABSTRACT
BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.
Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Sentinel Lymph Node Biopsy/methods , Neoadjuvant Therapy/methods , Axilla/pathology , Prospective Studies , Lymphatic Metastasis/pathology , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Lymph Node ExcisionABSTRACT
TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel that is predominantly localized to the membranes of late endosomes and lysosomes (LELs). Intracellular release of Ca2+ through TRPML1 is thought to be pivotal for maintenance of intravesicular acidic pH as well as the maturation, fusion, and trafficking of LELs. Interestingly, genetic ablation of TRPML1 in mice (Mcoln1-/- ) induces a hyperdistended/hypertrophic bladder phenotype. Here, we investigated this phenomenon further by exploring an unconventional role for TRPML1 channels in the regulation of Ca2+-signaling activity and contractility in bladder and urethral smooth muscle cells (SMCs). Four-dimensional (4D) lattice light-sheet live-cell imaging showed that the majority of LELs in freshly isolated bladder SMCs were essentially immobile. Superresolution microscopy revealed distinct nanoscale colocalization of LEL-expressing TRPML1 channels with ryanodine type 2 receptors (RyR2) in bladder SMCs. Spontaneous intracellular release of Ca2+ from the sarcoplasmic reticulum (SR) through RyR2 generates localized elevations of Ca2+ ("Ca2+ sparks") that activate plasmalemmal large-conductance Ca2+-activated K+ (BK) channels, a critical negative feedback mechanism that regulates smooth muscle contractility. This mechanism was impaired in Mcoln1-/- mice, which showed diminished spontaneous Ca2+ sparks and BK channel activity in bladder and urethra SMCs. Additionally, ex vivo contractility experiments showed that loss of Ca2+ spark-BK channel signaling in Mcoln1-/- mice rendered both bladder and urethra smooth muscle hypercontractile. Voiding activity analyses revealed bladder overactivity in Mcoln1-/- mice. We conclude that TRPML1 is critically important for Ca2+ spark signaling, and thus regulation of contractility and function, in lower urinary tract SMCs.
Subject(s)
Calcium Channels/metabolism , Calcium/metabolism , Muscle Contraction , Muscle, Smooth/metabolism , Myocytes, Smooth Muscle/metabolism , Transient Receptor Potential Channels/metabolism , Urinary Tract Physiological Phenomena , Animals , Biomarkers , Fluorescent Antibody Technique , Gene Expression , Intracellular Space/metabolism , Male , Membrane Potentials , Mice , Mice, Knockout , Muscle Contraction/genetics , Protein Transport , Transient Receptor Potential Channels/genetics , Urinary Bladder/metabolism , Urinary Bladder/physiopathologyABSTRACT
BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Mastectomy, Segmental/methods , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Combined Modality Therapy , Female , Humans , Intraoperative Care , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome , Tumor Burden , Whole-Body IrradiationABSTRACT
The RET receptor tyrosine kinase is crucial for the development of the enteric nervous system (ENS), acting as a receptor for Glial cell line-derived neurotrophic factor (GDNF) via GFR co-receptors. Drosophila has a well-conserved RET homolog (Ret) that has been proposed to function independently of the Gfr-like co-receptor (Gfrl). We find that Ret is required for development of the stomatogastric (enteric) nervous system in both embryos and larvae, and its loss results in feeding defects. Live imaging analysis suggests that peristaltic waves are initiated but not propagated in mutant midguts. Examination of axons innervating the midgut reveals increased branching but the area covered by the branches is decreased. This phenotype can be rescued by Ret expression. Additionally, Gfrl shares the same ENS and feeding defects, suggesting that Ret and Gfrl might function together via a common ligand. We identified the TGFß family member Maverick (Mav) as a ligand for Gfrl and a Mav chromosomal deficiency displayed similar embryonic ENS defects. Our results suggest that the Ret and Gfrl families co-evolved before the separation of invertebrate and vertebrate lineages.
Subject(s)
Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/growth & development , Drosophila melanogaster/genetics , Enteric Nervous System/growth & development , GPI-Linked Proteins/metabolism , Proto-Oncogene Proteins c-ret/genetics , Transforming Growth Factor beta/metabolism , Alleles , Animals , Animals, Genetically Modified , COS Cells , Chlorocebus aethiops , Drosophila melanogaster/metabolism , Enteric Nervous System/embryology , Enteric Nervous System/metabolism , GPI-Linked Proteins/genetics , Genes, Insect , Ligands , Mutation , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-ret/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Signal TransductionABSTRACT
BACKGROUND: Although rates of total skin-sparing (nipple-sparing) mastectomies are increasing, the oncologic safety of this procedure has not been evaluated in invasive lobular carcinoma (ILC). ILC is the second most common type of breast cancer, and its diffuse growth pattern and high positive margin rates potentially increase the risk of poor outcomes from less extensive surgical resection. METHODS: We compared time to local recurrence and positive margin rates in a cohort of 300 patients with ILC undergoing either total skin-sparing mastectomy (TSSM), skin-sparing mastectomy, or simple mastectomy between the years 2000-2020. Data were obtained from a prospectively maintained institutional database and were analyzed by using univariate statistics, the log-rank test, and multivariate Cox proportional hazards models. RESULTS: Of 300 cases, mastectomy type was TSSM in 119 (39.7%), skin-sparing mastectomy in 52 (17.3%), and simple mastectomy in 129 (43%). The rate of TSSM increased significantly with time (p < 0.001) and was associated with younger age at diagnosis (p = 0.0007). There was no difference in time to local recurrence on univariate and multivariate analysis, nor difference in positive margin rates by mastectomy type. Factors significantly associated with shorter local recurrence-free survival were higher tumor stage and tumor grade. CONCLUSIONS: TSSM can be safely offered to patients with ILC, despite the diffuse growth pattern seen in this tumor type.
Subject(s)
Breast Neoplasms , Carcinoma, Lobular , Mammaplasty , Breast Neoplasms/surgery , Carcinoma, Lobular/surgery , Humans , Mastectomy , Neoplasm Recurrence, Local/surgery , Nipples/surgery , Organ Sparing Treatments , Retrospective StudiesABSTRACT
PURPOSE: Clinical trials have shown that axillary lymph node dissection (ALND) can be avoided for many breast cancer patients with limited nodal involvement. However, whether its omission is safe for those with invasive lobular carcinoma (ILC) is still questioned. We sought to evaluate the impact of ALND on recurrence-free survival (RFS) by extent of nodal disease in patients with ILC. METHODS: We performed a retrospective, cross-sectional analysis of ILC patients treated between 1990 and 2019 at our institution. Patients underwent either breast conservation surgery (BCS) or mastectomy. We used univariate and multivariate statistics in Stata 14.2 to evaluate associations between extent of axillary surgery and time to recurrence stratified by nodal burden. RESULTS: Of 520 cases, 387 (78.4%) were node negative, 74 (14.9%) had 1-2 positive nodes, and 59 (11.4%) had three or more positive nodes. Most patients (93.3%) had hormone receptor-positive disease, and 94.8% had low or intermediate-grade tumors. The rate of ALND significantly decreased over time (p < 0.002). Using a multivariate model, there was no significant difference in RFS estimates based on receipt of ALND (HR = 0.53, 95% CI 0.17-1.64, p = 0.27), which also held true for patients with 1-2 positive nodes using a test of interaction (HR = 0.91, 95% CI 0.12-6.76, p = 0.92). CONCLUSIONS: These findings support the safety of omitting ALND in selected patients with ILC. Further studies of axillary management in ILC and imaging tools to predict nodal involvement and therapeutic response are warranted.
Subject(s)
Breast Neoplasms , Carcinoma, Lobular , Axilla/pathology , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Cross-Sectional Studies , Dissection , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Mastectomy , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Retrospective Studies , Sentinel Lymph Node BiopsyABSTRACT
PURPOSE: Pleomorphic invasive lobular carcinoma (ILC) has long been thought to have worse outcomes than classic ILC and is therefore often treated with chemotherapy. However, recent data question the utility of the pleomorphic designation, as the poor outcomes seen may be related to other associated high-risk features. Importantly, mitotic count may better define a subset of ILC with high risk of recurrence. We sought to determine the impact of pleomorphic histology versus mitotic count on disease-free survival (DFS) in pure ILC. Additionally, we evaluated whether pleomorphic histology was associated with receipt of chemotherapy when adjusting for other factors. METHODS: We analyzed a cohort of 475 patients with stage I-III pure ILC. We used Kaplan-Meier estimates, and Cox proportional hazards and logistic regression for multivariate analyses. Pleomorphic histology was confirmed by central pathology review. RESULTS: In a multivariate model, pleomorphic histology was not associated with reduced DFS. Only mitotic score, receptor subtype, and pathologic stage were independently and significantly associated with DFS. Patients with pleomorphic ILC were significantly more likely to receive chemotherapy than patients with classic ILC (adjusted odds ratio 2.96, p = 0.026). CONCLUSIONS: The pleomorphic designation in ILC does not have clinical utility and should not be used to determine therapy. Rather, mitotic count identified clear prognostic groups in this cohort of pure ILC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Carcinoma, Lobular/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/mortality , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Middle Aged , Mitotic Index , Neoplasm Invasiveness , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival RateABSTRACT
In the original article the authors' disclosures were incomplete.
ABSTRACT
BACKGROUND: The frequency of "exhausted" or checkpoint-positive (PD-1+CTLA-4+) cytotoxic lymphocytes (Tex) in the tumor microenvironment is associated with response to anti-PD-1 therapy in metastatic melanoma. The current study determined whether pretreatment Tex cells in locally advanced melanoma predicted response to neoadjuvant anti-PD-1 blockade. METHODS: Pretreatment tumor samples from 17 patients with locally advanced melanoma underwent flow cytometric analysis of pretreatment Tex and regulatory T cell frequency. Patients who met the criteria for neoadjuvant checkpoint blockade were treated with either PD-1 monotherapy or PD-1/CTLA-4 combination therapy. Best overall response was evaluated by response evaluation criteria in solid tumors version 1.1, with recurrence-free survival (RFS) calculated by the Kaplan-Meier test. The incidence and severity of adverse events were tabulated by clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. RESULTS: Of the neoadjuvant treated patients, 10 received anti-PD-1 monotherapy and 7 received anti-CTLA-4/PD-1 combination therapy. Of these 17 patients, 12 achieved a complete response, 4 achieved partial responses, and 1 exhibited stable disease. Surgery was subsequently performed for 11 of the 17 patients, and 8 attained a complete pathologic response. Median RFS and overall survival (OS) were not reached. Immune-related adverse events comprised four grade 3 or 4 events, including pneumonitis, transaminitis, and anaphylaxis. CONCLUSION: The results showed high rates of objective response, RFS, and OS for patients undergoing immune profile-directed neoadjuvant immunotherapy for locally advanced melanoma. Furthermore, the study showed that treatment stratification based upon Tex frequency can potentially limit the adverse events associated with combination immunotherapy. These data merit further investigation with a larger validation study.
Subject(s)
Immune Checkpoint Inhibitors , Immunotherapy , Melanoma , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Kaplan-Meier Estimate , Melanoma/immunology , Melanoma/therapy , Neoadjuvant Therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Tumor MicroenvironmentABSTRACT
BACKGROUND: Sentinel lymph node biopsy (SLNB) is a highly accurate method for staging the axilla in early breast cancer. Superparamagnetic iron oxide mapping agents have been explored to overcome the disadvantages of the standard SLNB technique, which uses a radioisotope tracer with or without blue dye. One such agent, Sienna+, was shown to be non-inferior to the standard technique for SLNB in a number of studies. The SentimagIC trial was designed to establish the non-inferiority of a new formulation of this magnetic tracer, Magtrace (formerly SiennaXP). METHODS: Patients with clinically node-negative early-stage breast cancer were recruited from six centers in the US. Patients received radioisotope and isosulfan blue dye injections, followed by an intraoperative injection of magnetic tracer, prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate non-inferiority and concordance. RESULTS: Data were collected for 146 procedures in 146 patients. The per patient detection rate was 99.3% (145/146) when using the magnetic tracer and 98.6% (144/146) when using the standard technique, while the nodal detection rate was 94.3% (348/369 nodes) when using the magnetic tracer and 93.5% (345/369) when using the standard technique (difference 0.8%, 95% binomial confidence interval lower bound - 2.1%). Of the 22 patients with positive sentinel lymph nodes (SLNs), 21 (95.4%) were detected by both the magnetic tracer and the standard technique. All malignant nodes detected by standard technique were also identified by the magnetic technique. CONCLUSION: The magnetic technique is non-inferior to the standard technique of radioisotope and blue dye for axillary SLN detection in early-stage breast cancer. The magnetic technique is therefore a viable alternative.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Ferric Compounds , Magnetite Nanoparticles , Rosaniline Dyes , Sentinel Lymph Node/pathology , Technetium , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/surgery , Equivalence Trials as Topic , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prospective Studies , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node BiopsyABSTRACT
OBJECTIVE. The objective of this study was to evaluate the feasibility of using a magnetic seed system for preoperative localization of axillary lymph nodes in patients with breast cancer. MATERIALS AND METHODS. We performed a retrospective analysis that included patients with breast cancer who underwent preoperative magnetic seed localization of axillary lymph nodes at our institution between January 1, 2017, and January 1, 2019. Magseed (Endomag) is a nonradioactive inducible magnetic seed that is induced to become a magnet when under the influence of its detector in the operating room. Clinical history, prior axillary sampling and clip placement, and procedure details and surgical outcomes were determined from a search of our PACS and electronic medical records. RESULTS. Thirty-five patients (34 women and one man) composed our study cohort. The mean patient age was 56 years (range, 32-78 years). One patient underwent two separate consecutive localizations for two separate operations, and another patient had bilateral lesions, for a total of 37 axillary lymph node localizations. One case of seed misplacement occurred during the ultrasound-guided localization procedure, resulting in immediate placement of a second seed, for a total of 38 Magseeds placed. All seeds were placed under ultrasound guidance. The mean number of days from seed placement to surgery was 5 days (range, 0-31 days). Thirty-seven of 38 Magseeds (97%) were documented to be successfully retrieved in the operating room. CONCLUSION. Magseed localization appears to be a safe, nonradioactive way to accurately localize axillary lymph nodes preoperatively.
Subject(s)
Axilla/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Fiducial Markers , Lymphatic Metastasis/diagnostic imaging , Magnetics , Adult , Aged , Axilla/pathology , Breast Neoplasms/pathology , Feasibility Studies , Female , Humans , Lymphatic Metastasis/pathology , Magnetic Resonance Imaging , Middle Aged , Preoperative Care , Retrospective StudiesABSTRACT
BACKGROUND: Invasive lobular carcinoma (ILC) of the breast grows in a diffuse pattern, making complete surgical excision difficult. This results in high rates of positive margins and low rates of successful breast-conserving surgery. We hypothesized that utilizing oncoplastic surgical techniques and selective shave margins would be associated with lower positive margin rates and increased breast conservation in women with ILC. METHODS: We performed a retrospective cross-sectional analysis in a large cohort of prospectively collected ILC cases who received surgical treatment at the University of California, San Francisco, between 1992 and 2017. We identified all patients with histologically proven, unilateral or bilateral, stage 1-3 ILC. The primary outcome was positive margin rates, defined as no ink on tumor. RESULTS: We identified 365 tumors in 358 women, with an average age of 61 years, who underwent breast-conserving surgery, and found that the use of oncoplastic techniques (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.21-0.79, p = 0.008) and the selective use of shave margins (OR 0.393, 95% CI 0.22-0.7, p = 0.002) were significantly associated with lower positive margin rates, when adjusted for tumor size and multifocality. The success rate for breast-conservation surgery was 75%, with a 25% conversion rate to mastectomy. CONCLUSIONS: Surgeons should consider routine use of oncoplastic techniques and shave margins when performing breast-conservation surgery for women with ILC as these methods are associated with significantly lower odds of having positive margins and higher breast-conservation rates.
Subject(s)
Breast Neoplasms/surgery , Carcinoma, Lobular/surgery , Mastectomy, Segmental/mortality , Neoplasm Recurrence, Local/prevention & control , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/pathology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Invasiveness , Prognosis , Prospective Studies , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival RateABSTRACT
OBJECTIVE: The purpose of this study is to evaluate a nonradioactive inducible magnetic seed system (Magseed, Endomag) for preoperative localization of nonpalpable breast lesions. CONCLUSION: All of the 73 seeds placed in the first 4 months of clinical use were successfully placed and all were successfully retrieved intraoperatively. The mean time from seed placement to surgery was 3 days. Early clinical experience suggests that Magseed is an effective and accurate means of preoperative breast lesion localization.
Subject(s)
Breast Neoplasms/diagnostic imaging , Fiducial Markers , Magnetics , Adult , Aged , Aged, 80 and over , Biopsy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Equipment Design , Female , Humans , Mammography , Middle Aged , Stainless Steel , Ultrasonography, MammaryABSTRACT
BACKGROUND: Many patients undergoing total-skin sparing mastectomy (TSSM) and 2-staged expander-implant (TE-I) reconstruction require postmastectomy radiation therapy (PMRT). Additionally, many patients undergoing TSSM for recurrent cancer have a history of lumpectomy and radiation therapy (XRT). Few studies have looked at the impact of XRT on the stages of TE-I reconstruction. METHODS: Patients undergoing TSSM and immediate TE-I reconstruction between 2006 and 2013 were identified from a prospectively maintained database. Rates of TE-I loss and severe infection requiring intravenous antibiotics were compared in patients with prior XRT (85 cases) and PMRT (133 cases). Complications were divided by stage of reconstruction: first stage (TSSM and TE placement) and second stage (TE-I exchange). RESULTS: Mean follow-up time was 2.5 years. Patients with prior XRT had more complications after the first stage of reconstruction than the second (TE-I loss: 15% vs 5%, P = 0.03; infection: 20% vs 8%, P = 0.04). Patients receiving PMRT had low complication rates after the first stage, when they had not yet received radiation (TE-I loss: 2%; infection: 5%). However, complication rates after TE-I exchange (TE-I loss, 18%; infection, 31%) were significantly higher, and nearly 4-fold higher than patients with prior XRT. CONCLUSIONS: Patients with prior XRT are at high risk for complications after the first stage of TE-I reconstruction after TSSM; however, the risk of complications at the second stage is comparable to patients without radiation exposure and significantly lower than patients receiving PMRT. Patients receiving radiation therapy should be given appropriate preoperative counseling regarding their risks.
Subject(s)
Breast Implantation , Breast Neoplasms/radiotherapy , Mastectomy, Subcutaneous , Postoperative Complications/etiology , Tissue Expansion , Adult , Aged , Breast Implantation/instrumentation , Breast Implantation/methods , Breast Implants , Breast Neoplasms/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors , Tissue Expansion/instrumentation , Tissue Expansion/methods , Tissue Expansion Devices , Treatment OutcomeABSTRACT
Most newly diagnosed ductal carcinoma in situ (DCIS) is treated with breast-conserving surgery (BCS) ± radiation therapy (RT). A key challenge is deciding whether or not to include RT with BCS. This decision is often determined by the degree of risk associated with disease recurrence. However, methods for risk assessment have not kept pace with diagnostic advances. The DCIS Score is an independent predictor and quantifier of individualized recurrence risk in patients with DCIS. Although the test is the only available genomic classifier for DCIS, the degree of adoption is varied, and it has not yet been fully accepted as standard practice. Recognizing the importance of individualizing recurrence assessment in patients with DCIS, the authors convened to review relevant clinical data, share best practices, and establish recommendations regarding how the assay should be incorporated into the decision-making process. Based on their clinical experiences, the authors concluded that effective integration of the DCIS Score should involve shared decision-making between surgeons and other specialties (radiation oncologists, pathologists, patient navigators, and physician assistants), with the patient's preference being a primary consideration. This manuscript aims to provide easy-to-use, clear-cut, and practical guidance to help physicians utilize the DCIS Score to improve risk assessment and inform treatment decisions for their patients with DCIS, including how to understand, run, interpret, and communicate the actionable results to patients.
Subject(s)
Breast Neoplasms/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , Breast Neoplasms/therapy , Carcinoma, Intraductal, Noninfiltrating/therapy , Decision Making , Female , Genomics , Humans , Neoplasm Recurrence, Local , Patient Education as Topic , Risk AssessmentABSTRACT
BACKGROUND AND OBJECTIVES: Invasive chest wall recurrences (CWR) following mastectomy are typically treated with surgical excision, radiation therapy (RT) to the chest wall and supraclavicular (SCV) region, and appropriate systemic therapy. Repeat axillary surgery is not routinely performed if the axilla is clinically negative. We evaluated sentinel node biopsy (SNB) in patients with an isolated invasive CWR, for identification and biopsy rates, non-axillary drainage, and clinical implications for radiation fields and outcome. METHODS: Between 2008 and 2013, 12/19 women with an isolated invasive CWR had sentinel node (SN) mapping with Tc99m. Median age was 53 years, and 92% (11/12) had initial path N0 disease. All had prior SNB, with axillary dissection in one patient. RESULTS: Overall, 83% (10/12) had successful mapping, with 70% (7/10) having an axillary SN. Ninety percent (9/10) had successful axillary node biopsy, with one patient having positive nodes. SCV RT was omitted in those with negative axillary nodes. With a median follow-up of 4.6 years from recurrence, there have been no SCV recurrences and no instances of lymphedema. CONCLUSIONS: SNB is possible in women with an isolated CWR with acceptable identification and biopsy rates. Omission of routine irradiation of the SCV region has not jeopardized regional control and results in decreased morbidity.