Minimizing re-excision after breast conserving surgery - a review of radiofrequency spectroscopy for real-time, intraoperative margin assessment.

INTRODUCTION: For early-stage breast cancer, breast-conserving surgery (BCS) plus radiation is standard-of-care. Nationwide, >20% of BCS patients require re-excision for positive margins, resulting in delayed adjuvant therapy, increased complications, emotional and financial stress for patients, and additional cost to the healthcare system. Although several methods may be employed to mitigate positive margins, no technique can fully address the need. MarginProbe® is an adjunctive tool for real-time intraoperative margin assessment and is shown to reduce positive margins by >50%. AREAS COVERED: Discussion of the impact of re-excision following BCS, a review of currently available methods for intraoperative margin management, followed by a technology and literature review of the MarginProbe® Radiofrequency Spectroscopy System. EXPERT OPINION: Re-excision significantly impacts patients, providers and payers. Limitations in the ability to assess margins at time of surgery warrant more advanced methods of residual disease detection. MarginProbe facilitates the most efficient pathway for breast cancer patients through the surgical phase of treatment. The device is well-suited for adoption as the healthcare focus shifts from volume to value and supports the three pillars of the US Department of Health and Human Services' 'Triple-Aim' strategy: improve population health, improve patient experience of care, and reduce per-capita costs.

Breast cancer differential diagnosis using diffuse optical spectroscopic imaging and regression with z-score normalized data.

SIGNIFICANCE: Current imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues. AIM: DOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts. METHODS: We performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were z-score normalized to the patient's contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions. RESULTS: Models incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) ≥0.85. Z-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data. CONCLUSIONS: Findings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality's inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.

Mastectomy Incision Design to Optimize Aesthetic Outcomes in Breast Reconstruction.

BACKGROUND: Choosing the optimal mastectomy incision must account for oncologic, reconstructive, and aesthetic considerations, including nipple preservation, mastectomy skin margins and potential for skin involvement, mastectomy skin perfusion and viability, mastectomy skin excess, previous breast scars, the reconstructive plan, and inconspicuous new scar placement. In the present study, we aimed to assess breast reconstruction aesthetics, as they are influenced by mastectomy incision design. METHODS: Nine commonly utilized mastectomy incision patterns were grouped into 3 categories: hidden scar, vertical scar, and transverse scar. Twenty plastic surgeons were asked to blindly grade before and after photographs of reconstructed breasts with regard to scar visibility and position and according to their influence on breast aesthetics. RESULTS: Statistically significant differences were observed between the study groups. Mastectomies and reconstructions performed through hidden incisions yield the most aesthetic results. Vertical scars are favorable to transverse scars. In the case of bilateral reconstructions, symmetric scar placement is paramount to optimizing aesthetic outcomes. CONCLUSIONS: The mastectomy incision pattern significantly affects the aesthetic outcomes in breast reconstruction. Patterns borrowed from cosmetic breast surgery consistently yield highly aesthetic outcomes. Surgeons must consider oncologic factors and patient characteristics in choosing an ideal incision for each patient.

Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy.

Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, ? a , and reduced scattering, ? s ? ) and blood flow (blood flow index, BFI), respectively. DOSI-derived ? a values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin ( HbO 2 , HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 ?? mm ? 1 (37%) in ? s ? and 0.003 ?? mm ? 1 (33%) in ? a lead to ? 53 % and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and

The impact of use of an intraoperative margin assessment device on re-excision rates.

Historically there has been a high rate of surgical interventions to obtain clear margins for breast cancer patients undergoing breast conserving local therapy. An intraoperative margin assessment tool (MarginProbe) has been approved for use in the US since 2013. This study is the first compilation of data from routine use of the device, to assess the impact of device utilization on re-excision rates. We present a retrospective, observational, review from groups of consecutive patients, before and after the implementation of intraoperative use of the device during lumpectomy procedures. Lesions were localized by standard methods. The intraoperative margin assessment device was used on all circumferential margins of the main specimen, but not on any additional shavings. A positive reading by the device led to an additional shaving of the corresponding cavity location. Specimens were also, when feasible, imaged intra-operatively by X-ray, and additional shavings were taken if needed based on clinical assessment. For each surgeon, historical re-excision rates were established based on a consecutive set of patients from a time period proximal to initiation of use of the device. From March 2013 to April 2014 the device was routinely used by 4 surgeons in 3 centers. In total, 165 cases lumpectomy cases were performed. Positive margins resulted in additional re-excision procedures in 9.7% (16/165) of the cases. The corresponding historical set from 2012 and 2013 consisted of 186 Lumpectomy cases, in which additional re-excision procedures were performed in 25.8% (48/186) of the cases. The reduction in the rate of re-excision procedures was significant 62% (P < 0.0001). Use of an intraoperative margin assessment device contributes to achieving clear margins and reducing re-excision procedures. As in some cases positive margins were found on shavings, future studies of interest may include an analysis of the effect of using the device on the shavings intra-operatively.

Tungsten targets the tumor microenvironment to enhance breast cancer metastasis.

The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients' years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans.

Metastatic lobular breast carcinoma infiltrating a uterine leiomyoma.

Metastatic breast cancer is rarely identified in a uterine leiomyoma. Herein is reported the case of a 53-year-old patient with untreated left-sided breast cancer who later manifested abdominal symptoms and metrorrhagia. After hysterectomy, pathologic analysis revealed metastatic lobular breast carcinoma involving the uterine fundus and a leiomyoma.