Staged Nipple Delay Procedure Expands Candidacy for Nipple-Sparing Mastectomy.

BACKGROUND: Nipple delay (ND) is a staged procedure that improves nipple-areolar complex (NAC) viability in nipple-sparing mastectomy (NSM) patients who are high-risk for NAC or skin-flap necrosis. This study compared postoperative outcomes and risk factors between patients treated with ND-NSM and NSM alone. METHODS: Patient demographics, risk factors for NAC or skin-flap necrosis, tumor characteristics, and operative outcomes were compared between ND-NSM and NSM groups from 2009 to 2023. Univariate and multivariate analyses were performed to identify significant variables associated with NAC or skin-flap necrosis. RESULTS: Overall, 71 ND-NSM patients and 537 NSM patients were compared. ND-NSM patients had larger breasts (p < 0.01), body mass index ≥ 30 (p = 0.01), prior breast/chest wall radiation (XRT) [p < 0.01], prior breast operations (p < 0.01), less axillary surgery (p < 0.01), more autologous tissue reconstruction over implant-based reconstruction compared with NSM patients (p = 0.02), and more prophylaxis (p < 0.01). There were no statistically significant differences between groups in regard to infection, skin-flap necrosis, NAC necrosis, seromas, and hematomas. No patients in the ND-NSM group had NAC necrosis and 1 patient had skin-flap necrosis, compared with 17 and 13 patients in the NSM group, respectively (p = 0.24). On univariate analysis, prior XRT was associated with increased risk for skin-flap necrosis (p = 0.02). Multivariate analysis showed XRT was associated with skin-flap necrosis (p = 0.02) and any necrosis (p = 0.01). Breast size was associated with NAC or skin-flap necrosis (p = 0.04). CONCLUSION: Larger breasts and XRT were risk factors for NAC or skin-flap necrosis; however, despite having more risk factors, ND-NSM patients had very low rates of necrosis. Notably, no nipples were lost. A shared decision should be made with patients regarding the risks and benefits of ND-NSM.

A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Rapidly Growing Mycobacterium tuberculosis in the Form of Empyema Necessitans: A Case Report.

We present a case of rapidly growing disseminated Mycobacterium tuberculosis (MTB) that presented as an empyema necessitans (EN) in a 65-year-old woman with a single right lung transplant admitted for progressive dyspnea. While hospitalized, she had daily fevers and was found to have a right-sided chest wall abscess and pleural effusion. Acid-fast bacilli cultures from the abscess and pleural fluid grew MTB within 4 and 6 days, respectively. Blood cultures later grew MTB as well. Upon initiation of rifampin, isoniazid, pyrazinamide, and ethambutol, she developed hemorrhagic pancreatitis and distributive shock secondary to antituberculosis medications and disseminated MTB. Noteworthy features of this case include the rapid rate of MTB culture growth in less than a week, the development of a likely donor-derived MTB EN, and the clinical challenges of MTB screening and MTB infection management in a solid organ transplant recipient.

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years and Younger with Unilateral Operable Invasive Breast Cancer.

BACKGROUND: Young women with breast cancer (BC) have an increased risk of contralateral breast cancer (CBC) compared with older women. This may contribute to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads to improved outcomes. METHODS: A prospectively maintained database was reviewed. Patient and tumor characteristics, survival, and rate of CBC were compared in women age ≤40 years treated for unilateral Stage 1-3 BC from January 2000 through December 2013. RESULTS: Patients ranged in age from 20 to 40 (mean 36) years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the BCS and BM group had smaller, fewer node-positive (p = 0.02) and lower grade tumors (p < 0.01) compared with the UM group. With a median follow-up of 79 months, Disease-free survival was similar for patients treated with BM, BCS (p = 0.22), or UM (p = 0.75). OS was significantly worse in the patients treated with UM (0.02) but was not different between the BCS and BM groups. CBC incidence was 2% (5/263) in patients who underwent BCS or UM, and 0.4% (1/244) in patients without a germline genetic mutation. CONCLUSIONS: BCS and UM resulted in similar disease-free survival (DFS) as BM in patients age 40 years and younger with BC. BCS and BM had similar OS, whereas UM patients had worse OS. Invasive CBC incidence was less than 0.5% at 10 years in patients without identified germline genetic mutations.

Predicting nipple-areolar involvement using preoperative breast MRI and primary tumor characteristics.

BACKGROUND: Preoperative assessment of the nipple-areolar complex (NAC) is invaluable when considering nipple-sparing mastectomy. Our hypothesis is that breast magnetic resonance imaging (MRI) may predict involvement of the NAC with tumor. METHODS: Clinical, histopathologic, and imaging data were compiled for patients who underwent preoperative breast MRI followed by mastectomy or nipple-sparing mastectomy for malignancy between 2006 and 2009. Blinded rereview of all MRI studies was performed by a breast MRI imager and compared to initial MRI findings. Multivariate analysis identified variables predicting NAC involvement with tumor. RESULTS: Of 77 breasts, 18 (23 %) had tumor involving or within 1 cm of the NAC. The sensitivity of detecting histopathologically confirmed NAC involvement was 61 % with history and/or physical examination, and 56 % with MRI. Univariate analysis identified the following variables as significant for NAC involvement: large tumors near the nipple on preoperative MRI, node-positive disease, invasive lobular carcinoma, advanced histopathologic T stage, and neoadjuvant chemotherapy. On multivariate analysis, only tumor size >2 cm and distance from tumor edge to the NAC <2 cm on MRI maintained significance. Pearson correlation coefficient for MRI size compared to histopathologic size was 0.53 (P < 0.0001). CONCLUSIONS: MRI is not superior to thorough clinical evaluation for predicting tumor in or near the NAC. However, MRI-measured tumor size and distance from the NAC are correlated with increased risk of NAC involvement. The combination of preoperative history and physical examination, tumor characteristics, and breast MRI can aid the surgeon in predicting a tumor-involved nipple more than any single modality alone.

Preoperative breast MRI in the surgical treatment of ductal carcinoma in situ.

Accurate determination of the size or extent of ductal carcinoma in situ (DCIS) by imaging is uncertain, and incomplete resection of tumor results in involved margins in up to 81% of cases. This study examined the accuracy of magnetic resonance imaging (MRI) for assessment of DCIS size, and evaluated the effect of preoperative breast MRI on achievement of tumor-free surgical margins after breast-conserving surgery (BCS). One-hundred and fifty-eight female patients with DCIS were identified from a prospective database: 60 patients (62 cases) had preoperative breast MRI, and 98 patients did not have MRI. The accuracy of tumor size assessed by MRI was determined by comparison with histopathologic size. All patients underwent BCS initially. The rate of involved margins after resection was compared in MRI and no-MRI groups. The overall correlation between MRI size and histopathologic size was high (p < 0.0001). MRI assessment of size was significantly more accurate when DCIS was high grade (p < 0.0001) or intermediate grade (p = 0.005) versus low grade (p = 0.187). The rate of tumor-involved margins was not significantly different in MRI and no-MRI groups (30.7% and 24.7%, respectively; p = 0.414). The rate of mastectomy was significantly higher in the MRI group than the no-MRI group (17.7% versus 4.1%; p = 0.004). These findings indicate that MRI can detect DCIS, especially when lesions are high or intermediate grade, but that MRI does not accurately predict the size of DCIS. In this study, MRI did not improve the surgeon's ability to achieve clear margins following BCS.

Non-healing Wound After Mastopexy: Cautionary Case Report for a Unique Source of a Marjolin's Ulcer of the Breast.

Marjolin's ulcers (MUs) represent a unique degenerative process that results in malignancy. Classically, sites of previous burns are associated with MU but, in fact, any non-healing wound has been found to be a potential source of degeneration. Malignancies that arise include typically cutaneous squamous cell carcinoma (SCC), but SCC at the site of a previous wound is a more aggressive, lethal variant. This report represents a cautionary case of the management of an open wound and highlights a previously undescribed etiology of an MU in the breast.

Nipple-sparing mastectomy: where are we now?

Surgical treatment of breast cancer has evolved from radical mastectomy with routine removal of the nipple-areolar complex (NAC) to breast conservative therapy with preservation of the breast and NAC. When breast conservation is not appropriate or the patient desires mastectomy for risk reduction, conventional therapy still consists of mastectomy with removal of the NAC, followed by reconstruction. Rising interest in improved cosmesis has led to the introduction of the skin-sparing and nipple-sparing mastectomy (NSM) as potential alternatives to mastectomy. There has been much controversy regarding the oncologic safety of these procedures, and the NSM has also introduced a set of complications, such as nipple and areolar necrosis, that are not a concern with total mastectomy. From our review of the literature, we feel that NSM may be a viable option in the appropriate setting, and that its risks and complications are acceptable when compared to the traditional surgical treatment of breast cancer.

Intraoperative high-resolution anoscopy: a minimally invasive approach in the treatment of patients with Bowen's disease and results in a private practice setting.

Anal intraepithelial neoplasia III (AIN III) is a risk factor for anal cancer with poor curative results and high morbidity. High-resolution anoscopy (HRA) is a minimally invasive means of identifying and treating AIN III early. We retrospectively reviewed HRA in the treatment of AIN III in a community setting. From January 2002 through November 2005, 76 patients with AIN III diagnosed by anal Pap smear, colposcopy, or biopsy underwent HRA for diagnosis and treatment. Twenty-one patients with AIN III on initial HRA underwent follow-up HRA for reassessment and treatment at 6 months. Recurrence/persistence of disease was recorded and compared with patient characteristics. Of 21 patients with repeat HRA, four were HIV-negative and 17 were HIV-positive. Twelve of 21 (57%) had intraanal recurrence/persistence; nine of 21 (43%) had no AIN III. Eleven (92%) with recurrence were HIV-positive; one (8%) was HIV-negative. Three (75%) HIV-negative patients had no recurrence/persistence; one of four (25%) had recurrence; and 11 of 17 (65%) HIV-positive patients had persistence of disease. HRA is an alternative tool to treat AIN III and can be performed in a community setting yielding results comparable to the university setting. As the prevalence of AIN III increases, it will be more important for community surgeons to treat AIN III with HRA.

Data integration from pathology slides for quantitative imaging of multiple cell types within the tumor immune cell infiltrate.

BACKGROUND: Immune cell infiltrates (ICI) of tumors are scored by pathologists around tumor glands. To obtain a better understanding of the immune infiltrate, individual immune cell types, their activation states and location relative to tumor cells need to be determined. This process requires precise identification of the tumor area and enumeration of immune cell subtypes separately in the stroma and inside tumor nests. Such measurements can be accomplished by a multiplex format using immunohistochemistry (IHC). METHOD: We developed a pipeline that combines immunohistochemistry (IHC) and digital image analysis. One slide was stained with pan-cytokeratin and CD45 and the other slide with CD8, CD4 and CD68. The tumor mask generated through pan-cytokeratin staining was transferred from one slide to the other using affine image co-registration. Bland-Altman plots and Pearson correlation were used to investigate differences between densities and counts of immune cell underneath the transferred versus manually annotated tumor masks. One-way ANOVA was used to compare the mask transfer error for tissues with solid and glandular tumor architecture. RESULTS: The overlap between manual and transferred tumor masks ranged from 20%-90% across all cases. The error of transferring the mask was 2- to 4-fold greater in tumor regions with glandular compared to solid growth pattern (p < 10-6). Analyzing data from a single slide, the Pearson correlation coefficients of cell type densities outside and inside tumor regions were highest for CD4 + T-cells (r = 0.8), CD8 + T-cells (r = 0.68) or CD68+ macrophages (r = 0.79). The correlation coefficient for CD45+ T- and B-cells was only 0.45. The transfer of the mask generated an error in the measurement of intra- and extra- tumoral CD68+, CD8+ or CD4+ counts (p < 10-10). CONCLUSIONS: In summary, we developed a general method to integrate data from IHC stained slides into a single dataset. Because of the transfer error between slides, we recommend applying the antibody for demarcation of the tumor on the same slide as the ICI antibodies.

Comparison of outcomes of breast conserving therapy in multifocal and unifocal invasive breast cancer.

BACKGROUND: There is controversy about whether breast conserving therapy (BCT) should be contraindicated in multifocal (MF) breast cancer. Few studies have reported on the oncologic safety of BCT in MF breast cancer. STUDY DESIGN: We reviewed a prospective database of 1,169 women with invasive breast cancer who were treated with segmentectomy and whole breast irradiation from 1991 through 2009 and followed at our institution. Multifocal breast cancer was defined as 2 or more distinct tumors excised with a single incision or segmentectomy. We compared 2 groups, MF and unifocal breast cancer patients, with respect to demographics, tumor characteristics, adjuvant systemic therapy, local recurrence (LR), disease-free survival (DFS), and overall survival (OS). RESULTS: One hundred sixty-four patients with MF and 999 with unifocal invasive breast cancer were treated with BCT. Median follow-up was 112 months. Compared with the unifocal group, patients in the MF group had higher 10-year LR (0.6% vs 6.1%, p < 0.001) and lower 10-year DFS (97.7% vs 89.3%, p < 0.001) and OS (98.4% vs 85.8%, p < 0.001). On multivariable analysis, multifocality was independently significantly associated with local recurrence-free survival (LRFS), DFS, and OS. CONCLUSIONS: Our data suggest that BCT in MF breast cancer is oncologically safe but may result in a slightly inferior outcome compared with BCT in unifocal breast cancer.